Articoli di riviste: "SCD89"

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Berthelot, Laureline, Christina Papista, Thiago T. Maciel, Martine Biarnes-Pelicot, Emilie Tissandie, Pamela H. M. Wang, Houda Tamouza et al. "Transglutaminase is essential for IgA nephropathy development acting through IgA receptors". Journal of Experimental Medicine 209, n. 4 (26 marzo 2012): 793–806. http://dx.doi.org/10.1084/jem.20112005.

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IgA nephropathy (IgAN) is a common cause of renal failure worldwide. Treatment is limited because of a complex pathogenesis, including unknown factors favoring IgA1 deposition in the glomerular mesangium. IgA receptor abnormalities are implicated, including circulating IgA–soluble CD89 (sCD89) complexes and overexpression of the mesangial IgA1 receptor, TfR1 (transferrin receptor 1). Herein, we show that although mice expressing both human IgA1 and CD89 displayed circulating and mesangial deposits of IgA1–sCD89 complexes resulting in kidney inflammation, hematuria, and proteinuria, mice expressing IgA1 only displayed endocapillary IgA1 deposition but neither mesangial injury nor kidney dysfunction. sCD89 injection into IgA1-expressing mouse recipients induced mesangial IgA1 deposits. sCD89 was also detected in patient and mouse mesangium. IgA1 deposition involved a direct binding of sCD89 to mesangial TfR1 resulting in TfR1 up-regulation. sCD89–TfR1 interaction induced mesangial surface expression of TGase2 (transglutaminase 2), which in turn up-regulated TfR1 expression. In the absence of TGase2, IgA1–sCD89 deposits were dramatically impaired. These data reveal a cooperation between IgA1, sCD89, TfR1, and TGase2 on mesangial cells needed for disease development. They demonstrate that TGase2 is responsible for a pathogenic amplification loop facilitating IgA1–sCD89 deposition and mesangial cell activation, thus identifying TGase2 as a target for therapeutic intervention in this disease.

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Wu, Haiting, Xiaoyan Wang, Zhe Yang, Qing Zhao, Yubing Wen, Xuemei Li, Wei Zhang e Ruitong Gao. "Serum Soluble CD89-IgA Complexes Are Elevated in IgA Nephropathy without Immunosuppressant History". Disease Markers 2020 (16 gennaio 2020): 1–6. http://dx.doi.org/10.1155/2020/8393075.

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Purpose. CD89 (FcαRI), the receptor of IgA, can shed from cells to form complexes with IgA in serum and is supposed to participate in the pathogenesis of IgA nephropathy (IgAN). There are contradictory results on their utility in clinical practice. This study is aimed at investigating whether sCD89-IgA complexes can help in the diagnosis or evaluation of the disease. Methods. A sandwich ELISA was established using anti-CD89 as a capture antibody and HRP-conjugated anti-IgA as a detection antibody. This method was used to measure serum levels of sCD89-IgA complexes in IgAN patients without immunosuppressant history and healthy subjects. Correlations between serum levels of sCD89-IgA complexes and disease severity were analyzed. Results. Serum sCD89-IgA complexes increased with age (P<0.001). IgAN patients had higher sCD89-IgA complex levels compared with age- and gender-matched normal healthy individuals (P<0.001). Serum sCD89-IgAN significantly predicted IgAN diagnosis (AUC = 0.762 (0.640-0.883), P<0.001). But sCD89-IgA complexes did not correlate with baseline clinical manifestations, oxford classification, or renal function deteriorate speed. Conclusions. Serum sCD89-IgA complexes can guide diagnosis of IgAN in patients without immunosuppressant history, but provide limited help in clinicopathologic prediction.

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van Zandbergen, Ger, Ralf Westerhuis, Ngaisah Klar Mohamad, Jan G. J. van de Winkel, Mohamed R. Daha e Cees van Kooten. "Crosslinking of the Human Fc Receptor for IgA (FcαRI/CD89) Triggers FcR γ-Chain-Dependent Shedding of Soluble CD89". Journal of Immunology 163, n. 11 (1 dicembre 1999): 5806–12. http://dx.doi.org/10.4049/jimmunol.163.11.5806.

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Abstract CD89/FcαRI is a 55- to 75-kDa type I receptor glycoprotein, expressed on myeloid cells, with important immune effector functions. At present, no information is available on the existence of soluble forms of this receptor. We developed an ELISA for the detection of soluble CD89 (sCD89) forms and investigated the regulation of sCD89 production. PMA/ionomycin stimulation of monocytic cell lines (U937, THP-1, and MM6), but not of neutrophils, resulted in release of sCD89. Crosslinking of CD89 either via its ligand IgA or with anti-CD89 mAbs similarly resulted in sCD89 release. Using CD89-transfected cells, we showed ligand-induced shedding to be dependent on coexpression of the FcR γ-chain subunit. Shedding of sCD89 was dependent on signaling via the γ-chain and prevented by addition of inhibitors of protein kinase C (staurosporine) or protein tyrosine kinases (genistein). Western blotting revealed sCD89 to have an apparent molecular mass of 30 kDa and to bind IgA in a dose-dependent fashion. In conclusion, the present data document a ligand-binding soluble form of CD89 that is released upon activation of CD89-expressing cells. Shedding of CD89 may play a role in fine-tuning CD89 immune effector functions.

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Di Leo, Vincenzo, Patrick J. Gleeson, Fabio Sallustio, Carine Bounaix, Jennifer Da Silva, Gesualdo Loreto, Sanae Ben Mkaddem e Renato C. Monteiro. "Rifaximin as a Potential Treatment for IgA Nephropathy in a Humanized Mice Model". Journal of Personalized Medicine 11, n. 4 (16 aprile 2021): 309. http://dx.doi.org/10.3390/jpm11040309.

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IgA Nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by the mesangial deposition of abnormally glycosylated IgA1 (Gd-IgA). The production of Gd-IgA occurs in mucose-associated lymphoid tissue (MALT). The microbiota plays a role in MALT modulation. Rifaximin (NORMIX®), a non-absorbable oral antibiotic, induces positive modulation of the gut microbiota, favoring the growth of bacteria beneficial to the host. Here, we evaluate the effect of rifaximin on a humanized mice model of IgAN (α1KI-CD89Tg). Methods: The α1KI-CD89Tg mice were treated by the vehicle (olive oil) or rifaximin (NORMIX®). Serum levels of hIgA, hIgA1–sCD89, and mIgG–hIgA1 immune complexes were determined. Glomerular hIgA1 deposit and CD11b+ cells recruitment were revealed using confocal microscopy. Furthermore, the mRNA of the B-Cell Activating Factor (BAFF), polymeric immunoglobulin receptor (pIgR), and Tumor Necrosing Factor-α (TNF-α) in gut samples were detected by qPCR. Results: Rifaximin treatment decreased the urinary protein-to-creatinine ratio, serum levels of hIgA1–sCD89 and mIgG–hIgA1 complexes, hIgA1 glomerular deposition, and CD11b+ cell infiltration. Moreover, rifaximin treatment decreased significantly BAFF, pIgR, and TNF-α mRNA expression. Conclusions: Rifaximin decreased the IgAN symptoms observed in α1KI-CD89Tg mice, suggesting a possible role for it in the treatment of the disease.

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Esteve Cols, Clara, Freddzia-Amanda Graterol Torres, Bibiana Quirant Sánchez, Helena Marco Rusiñol, Maruja Isabel Navarro Díaz, Jordi Ara del Rey e Eva Mª Martínez Cáceres. "Immunological Pattern in IgA Nephropathy". International Journal of Molecular Sciences 21, n. 4 (18 febbraio 2020): 1389. http://dx.doi.org/10.3390/ijms21041389.

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The current gold-standard diagnostic technique for IgA nephropathy (IgAN), the leading form of primary glomerulonephritis, is renal biopsy. CD89 (the main IgA receptor) is expressed on the surface of monocytes and plays a role in disease pathogenesis. Immunocomplexes formed by sCD89 (soluble form) and Gd-IgA1 are related to disease prognosis. We hypothesize that reduced CD89 surface expression on monocytes may be a marker of disease severity. We aimed to analyze leukocyte subpopulations in peripheral blood and CD89 surface expression on monocytes in a prospective study of 22 patients and 12 healthy subjects (HS). Leukocyte subpopulations and CD89 expression were analyzed by flow cytometry. IgAN patients had a higher percentage of activated and effector memory CD4+ and CD8+ T lymphocytes, a lower percentage of transitional B lymphocytes and plasmablasts, and a higher percentage of CD56dimCD16+ NK cells and myeloid dendritic cells compared with HS. Correlations between reduced CD89 expression levels on nonclassical monocytes, histological findings of a poor prognosis on renal biopsy and baseline renal function were observed. IgAN patients show a characteristic immunological pattern in peripheral blood. A reduced expression level of CD89 on nonclassical monocytes identifies patients with a worse renal prognosis.

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Zych, Michał, Aleksander Roszczyk, Filip Dąbrowski, Monika Kniotek e Radosław Zagożdżon. "Soluble Forms of Immune Checkpoints and Their Ligands as Potential Biomarkers in the Diagnosis of Recurrent Pregnancy Loss—A Preliminary Study". International Journal of Molecular Sciences 25, n. 1 (29 dicembre 2023): 499. http://dx.doi.org/10.3390/ijms25010499.

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Immune checkpoints (ICPs) serve as regulatory switches on immune-competent cells. Soluble ICPs consist of fragments derived from ICP molecules typically located on cell membranes. Research has demonstrated that they perform similar functions to their membrane-bound counterparts but are directly present in the bloodstream. Effective control of the maternal immune system is vital for a successful pregnancy due to genetic differences between the mother and fetus. Abnormalities in the immune response are widely acknowledged as the primary cause of spontaneous abortions. In our research, we introduce a novel approach to understanding the immune-mediated mechanisms underlying recurrent miscarriages and explore new possibilities for diagnosing and preventing pregnancy loss. The female participants in the study were divided into three groups: RSA (recurrent spontaneous abortion), pregnant, and non-pregnant women. The analysis of soluble forms of immune checkpoints and their ligands in the serum of the study groups was conducted using the Luminex method Statistically significant differences in the concentrations of (ICPs) were observed between physiological pregnancies and the RSA group. Among patients with RSA, we noted reduced concentrations of sGalectin-9, sTIM-3, and sCD155, along with elevated concentrations of LAG-3, sCD80, and sCD86 ICPs, in comparison to physiological pregnancies. Our study indicates that sGalectin-9, TIM-3, sLAG-3, sCD80, sCD86, sVISTA, sNectin-2, and sCD155 could potentially serve as biological markers of a healthy, physiological pregnancy. These findings suggest that changes in the concentrations of soluble immune checkpoints may have the potential to act as markers for early pregnancy loss.

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Liu, Chao, Xiaohui Li, Aijie Li, Wenxue Zou, Rui Huang, Xiaoyu Hu, Jinming Yu, Xiaoling Zhang e Jinbo Yue. "Concurrent Chemoradiotherapy Increases the Levels of Soluble Immune Checkpoint Proteins in Patients with Locally Advanced Cervical Cancer". Journal of Immunology Research 2022 (4 aprile 2022): 1–8. http://dx.doi.org/10.1155/2022/9621466.

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Purpose. Concurrent chemoradiotherapy (CCRT) has been widely applied to locally advanced cervical cancer (LACC) patients, inducing the massive release of antigen and systematic immunomodulatory effects. However, its effect on the soluble immune checkpoint proteins (sICPs) remains unclear, which might play a key role in the immune response. Therefore, the current study explored changes in the levels of 16 sICPs in LACC patients during CCRT. Methods. We prospectively enrolled fifty-one LACC patients treated with CCRT and collected patients’ blood before, during and after CCRT. The levels of 16 sICPs were measured using the Luminex platform, and the changes were measured using Friedman test with Bonferroni’s posttest. One month after CCRT, the tumor response was evaluated according to the RECIST 1.1 guidelines. Results. The levels of soluble T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3) significantly increased during CCRT ( P = 0.041 ), while those of the soluble B and T lymphocyte attenuator (sBTLA), sCD40, soluble glucocorticoid-induced tumor necrosis factor receptor ligand (sGITRL), sCD80, sCD86, sPD-1, sPD-L1, sCTLA-4, and soluble inducible T-cell costimulator (sICOS) significantly increased after CCRT (all P < 0.05 ). Other sICPs showed no significant changes throughout the CCRT (all P > 0.05 ). 41 (80%), 8 (16%), and 2 (4%) patients showed complete response (CR), partial response (PR), and stable disease (SD) after CCRT, respectively. Interestingly, the level of soluble lymphocyte-activation gene 3 (sLAG-3) was significantly higher among the PR/SD patients as compared to the CR after CCRT ( P = 0.009 ). Conclusions. This study revealed that CCRT might elevate the serum levels of sTIM-3, sBTLA, sCD40, sGITRL, sCD80, sCD86, sPD-1, sPD-L1, sCTLA-4, and sICOS in the patients with LACC. The sLAG-3 level was higher in the patients with poor response to CCRT. These findings revealed the dynamic changes in the sICPs levels during CCRT, which might be helpful in designing optimal treatment strategies for LACC patients.

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Odagiri, Naoshi, Hoang Hai, Le Thi Thanh Thuy, Minh Phuong Dong, Maito Suoh, Kohei Kotani, Atsushi Hagihara et al. "Early Change in the Plasma Levels of Circulating Soluble Immune Checkpoint Proteins in Patients with Unresectable Hepatocellular Carcinoma Treated by Lenvatinib or Transcatheter Arterial Chemoembolization". Cancers 12, n. 8 (24 luglio 2020): 2045. http://dx.doi.org/10.3390/cancers12082045.

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Immune checkpoint inhibitors, combined with anti-angiogenic agents or locoregional treatments (e.g., transarterial chemoembolization (TACE)), are expected to become standard-of-care for unresectable hepatocellular carcinoma (HCC). We measured the plasma levels of 16 soluble checkpoint proteins using multiplexed fluorescent bead-based immunoassays in patients with HCC who underwent lenvatinib (n = 24) or TACE (n = 22) treatment. In lenvatinib-treated patients, plasma levels of sCD27 (soluble cluster of differentiation 27) decreased (p = 0.040) and levels of sCD40 (p = 0.014) and sTIM-3 (p < 0.001) were increased at Week 1, while levels of sCD27 (p < 0.001) were increased significantly at Weeks 2 through 4. At Week 1 of TACE, in addition to sCD27 (p = 0.028), sCD40 (p < 0.001), and sTIM-3 (soluble T-cell immunoglobulin and mucin domain–3) (p < 0.001), levels of sHVEM (soluble herpesvirus entry mediator) (p = 0.003), sTLR-2 (soluble Toll-like receptor 2) (p = 0.009), sCD80 (p = 0.036), sCTLA-4 (soluble cytotoxic T-lymphocyte antigen 4) (p = 0.005), sGITR (soluble glucocorticoid-induced tumor necrosis factor receptor) (p = 0.030), sGITRL (soluble glucocorticoid-induced TNFR-related ligand) (p = 0.090), and sPD-L1 (soluble programmed death-ligand 1) (p = 0.070) also increased. The fold-changes in soluble checkpoint receptors and their ligands, including sCTLA-4 with sCD80/sCD86 and sPD-1 (soluble programmed cell death domain–1) with sPD-L1 were positively correlated in both the lenvatinib and TACE treatment groups. Our results suggest that there are some limited differences in immunomodulatory effects between anti-angiogenic agents and TACE. Further studies from multicenters may help to identify an effective combination therapy.

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KAKOULIDOU, M., X. WANG, X. ZHAO, R. PIRSKANEN e A. LEFVERT. "Soluble costimulatory factors sCD28, sCD80, sCD86 and sCD152 in relation to other markers of immune activation in patients with myasthenia gravis". Journal of Neuroimmunology 185, n. 1-2 (aprile 2007): 150–61. http://dx.doi.org/10.1016/j.jneuroim.2007.01.007.

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Lin, Wei. "sCD83 alleviates experimental autoimmune uveitis through disrupting the regulation of Rab1a/LRRK2 on F-actin rearrangements". Journal of Immunology 202, n. 1_Supplement (1 maggio 2019): 116.2. http://dx.doi.org/10.4049/jimmunol.202.supp.116.2.

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Abstract A soluble form of CD83, generated from membrane CD83 by splice variants or by shedding, inhibites T-cell proliferation to regulatory the immune response in many autoimmune disease and organ-rejection treatment. However, the role of sCD83 in the autoimmune uveitis is still not clear. In our study, we show that sCD83 alleviates experimental autoimmune uveitis (EAU) through a novel mechanism. During onset and recovery of EAU, the level of sCD83 rises in the serum and aqueous humor. Systemic or topical application of sCD83 application alleviates the symptom of EAU and decreases the infiltrated inflammatory cells and cytokines. Mechanistically, sCD83 induces tolerogenic DCs by decreasing the synaptic expression of co-stimulatory molecules and hampering the cell contact between DCs and T cells. sCD83 disruptes the cytoskeletal rearrangements at the DC-T cell contact zone, leading to alter localization of co-stimulatory molecules and suppress T-cell activation. Furthermore, sCD83 is proved to enter into DCs through caveolin-dependent endocytic path-way. And then, sCD83 can bind with Rab1a to inhibit Rab1a-GTP activation, which further influence the regulation of LRRK2 on F-actin rearrangements. This pathway is different from the sCD83/TLR4/MD2 path-way. Thus, the ability of sCD83 to modulate DC-mediated inflammation in the eye could be harnessed to develop new immunosuppressive therapeutics for autoimmune uveitis.

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Zelek, Wioleta M., Lewis M. Watkins, Owain W. Howell, Rhian Evans, Sam Loveless, Neil P. Robertson, Marijke Beenes, Loek Willems, Ricardo Brandwijk e B. Paul Morgan. "Measurement of soluble CD59 in CSF in demyelinating disease: Evidence for an intrathecal source of soluble CD59". Multiple Sclerosis Journal 25, n. 4 (9 febbraio 2018): 523–31. http://dx.doi.org/10.1177/1352458518758927.

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Background: CD59, a broadly expressed glycosylphosphatidylinositol-anchored protein, is the principal cell inhibitor of complement membrane attack on cells. In the demyelinating disorders, multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), elevated complement protein levels, including soluble CD59 (sCD59), were reported in cerebrospinal fluid (CSF). Objectives: We compared sCD59 levels in CSF and matched plasma in controls and patients with MS, NMOSD and clinically isolated syndrome (CIS) and investigated the source of CSF sCD59 and whether it was microparticle associated. Methods: sCD59 was quantified using enzyme-linked immunosorbent assay (ELISA; Hycult; HK374-02). Patient and control CSF was subjected to western blotting to characterise anti-CD59-reactive materials. CD59 was localised by immunostaining and in situ hybridisation. Results: CSF sCD59 levels were double those in plasma (CSF, 30.2 ng/mL; plasma, 16.3 ng/mL). Plasma but not CSF sCD59 levels differentiated MS from NMOSD, MS from CIS and NMOSD/CIS from controls. Elimination of microparticles confirmed that CSF sCD59 was not membrane anchored. Conclusion: CSF levels of sCD59 are not a biomarker of demyelinating diseases. High levels of sCD59 in CSF relative to plasma suggest an intrathecal source; CD59 expression in brain parenchyma was low, but expression was strong on choroid plexus (CP) epithelium, immediately adjacent the CSF, suggesting that this is the likely source.

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Kang, Seon Mee, Jun Choul Lee e Bon Jeong Ku. "Changes in Soluble Serum CD81 Concentration during an Oral Glucose Tolerance Test in Patients with Diabetes Mellitus and Individuals with Normal Glucose Tolerance". Diagnostics 13, n. 23 (21 novembre 2023): 3500. http://dx.doi.org/10.3390/diagnostics13233500.

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Aim: Cluster of differentiation 81 (CD81) is a cell surface protein involved in cell development, activation, growth, and motility. Recent studies have suggested that CD81 is a marker of dedifferentiated β-cells under conditions of metabolic stress, such as progressive diabetes. However, the clinical significance of changes in soluble serum CD81 (sCD81) in diabetic individuals remains unknown. The aim of this study was to investigate whether serum sCD81 concentrations differ between subjects with diabetes and normal glucose tolerance (NGT), and whether sCD81 changes during a 75 g oral glucose tolerance test (OGTT). Materials and methods: We recruited 101 subjects who had completed an OGTT. According to the test results, the participants were divided into diabetes mellitus (DM) and NGT groups. Participants with prediabetes were excluded from the analysis. During the OGTT, sCD81 levels were measured at 0 and 120 min. We compared changes in sCD81 between the groups. Results: In the DM group, soluble sCD81 levels were significantly higher at baseline and 120 min in the OGTT compared with the normal group (0.59 (0.22–1.05) ng/mL vs. 0.25 (0.81–0.67) ng/mL, 0.55 (0.17–0.96) ng/mL vs. 0.21 (0.92–0.78) ng/mL, p = 0.006 and 0.029, respectively). The soluble sCD81 levels in the NGT group remained unchanged (p = 0.658), while those in the DM group were significantly decreased during the OGTT (p = 0.003). Conclusion: Soluble sCD81 levels were elevated in individuals with type 2 diabetes, such that changes in sCD81 were only observed during the OGTT in the DM group. Soluble sCD81 may have potential as a new diagnostic marker for type 2 diabetes.

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Liu, Shen, Chaoqun Huang, Dawei Li, Weihua Ren, Haoxing Zhang, Meiyan Qi, Xin Li e Long Yu. "Molecular cloning and expression analysis of a new gene for short-chain dehydrogenase/reductase 9." Acta Biochimica Polonica 54, n. 1 (20 febbraio 2007): 213–18. http://dx.doi.org/10.18388/abp.2007_3289.

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We report here the cloning and characterization of a novel human short-chain dehydrogenases/reductase gene SCDR9, isolated from a human liver cDNA library, and mapped to 4q22.1 by browsing the UCSC genomic database. SCDR9 containing an ORF with a length of 900 bp, encoding a protein with a signal peptide sequence and an adh_short domain. GFP localization shows SCDR9 protein concentrated in some site of the cytoplasm, but not in the ER. Expression pattern in eighteen tissues revealed that SCDR9 is expressed highly in liver. Soluble recombinant protein was successfully purified from Escherichia coli using pET28A(+) expression vector. Our data provides important information for further study of the function of the SCDR9 gene and its products.

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Einenkel, Rebekka, Katrin Regina Helene Packhäuser, Jens Ehrhardt, Anne Tüngler, Marek Zygmunt e Damián Oscar Muzzio. "CD83 is locally regulated and differentially expressed in disturbed murine pregnancy". Reproduction 158, n. 4 (ottobre 2019): 323–33. http://dx.doi.org/10.1530/rep-19-0171.

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Alterations in the immunologic balance during pregnancy have been associated with poor pregnancy outcomes. The underlying mechanisms are complex and mouse models delivered valuable information on inflammatory imbalance in disturbed pregnancies and served as model to test potential anti-inflammatory therapies. CD83 is a transmembrane protein (mCD83) with a soluble form (sCD83) which possesses strong anti-inflammatory properties. During murine pregnancy, upregulated mCD83 expression induces sCD83 release after in vitro stimulation with LPS, phorbol myristate acetate (PMA) and ionomycin. The release mechanism of sCD83 and its control are yet to be elucidated. In this study, the expression of mCD83 and sCD83 has been extensively studied in the CBA/J × DBA/2J mouse model of pro-inflammatory-mediated pregnancy disturbances. mCD83 was higher expressed on splenic B cells, uterus-draining lymph nodes T cells and dendritic cells from mice with poor pregnancy outcome (PPOM) compared to mice with good pregnancy outcome (GPOM). PPOM, however, was accompanied by lower sCD83 serum levels. In vitro treatment of splenic B cells with progesterone led to a reduction of TIMP1 expression, mCD83 expression and sCD83 release, while TIMP1 treatment had a positive effect on sCD83 availability. These results suggest that tissue and matrix components are involved in the regulation of CD83 in murine pro-inflammatory pregnancies.

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Linker-Israeli, M., S. Hyun, T. Ozeri-Chen, D. J. Wallace, K. Banks e J. R. Klinenberg. "Elevated in vivo and in vitro secretion of CD8-alpha molecules in patients with systemic lupus erythematosus." Journal of Immunology 152, n. 6 (15 marzo 1994): 3158–67. http://dx.doi.org/10.4049/jimmunol.152.6.3158.

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Abstract Endogenously activated CD8+ cells contribute to the aberrant immune regulation that characterizes SLE. Because stimulation of CD8+ cells with lectin/Ag triggers release of CD8-alpha molecules (sCD8), we measured, in patients with SLE, serum sCD8 content, its correlation with disease activity, and the in vitro release of sCD8 by SLE PBMCs. sCD8 levels, measured by ELISA in sera of 50 SLE patients, were higher than normal in 16 out of 21 mildly active and 15 out of 15 active SLE patients. sCD8 correlated positively with the clinical index for disease activity (r = 0.57, p = 0.001) and with sIL-2R levels (r = 0.52, p < 0.0001), and negatively with serum C3 levels (r = -0.5, p < 0.04). Freshly isolated SLE PBMCs had higher than normal CD8-alpha mRNA levels and secreted high levels of sCD8 in vitro (p < 0.05 vs control PBMC). sCD8 in vitro release by SLE PBMCs may be modulated by non-CD8+ cells. Thus, anti-CD2 mAb inhibited sCD8 release, whereas anti-HLA mAb increased it in unseparated PBMCs, but not in CD8+ enriched cultures. Moreover, sCD8 release increased significantly in PBMC cultures enriched for CD8+ DR+ cells by negative selection. Added-back monocytes decreased sCD8 to original levels, but not after glutaraldehyde fixation, nor in the presence of anti-HLA mAb. Further, lectin-induced IgG production and proliferation were reduced in the presence of sCD8, suggesting that the soluble CD8 molecules may be immunoregulatory. Because the high sCD8 levels in sera of active SLE likely reflect pathogenic cell activation, serum CD8 content may be an additional serologic activity marker, and its study could provide insights into mechanisms of disease.

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Gong, Xingyu, Tianyi Ma, Qiaoya Zhang, Yanhong Wang, Chengchuang Song, Min Lai, Chunlei Zhang, Xingtang Fang e Xi Chen. "Porcine Reproductive and Respiratory Syndrome Virus Modulates the Switch of Macrophage Polarization from M1 to M2 by Upregulating MoDC-Released sCD83". Viruses 15, n. 3 (17 marzo 2023): 773. http://dx.doi.org/10.3390/v15030773.

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Porcine reproductive and respiratory syndrome virus (PRRSV), the most economically important infectious disease of pigs, elicits poor innate and adaptive immune responses. Soluble CD83 (sCD83), a secretion from various immune cell populations, especially MoDCs, is involved in negatively regulating the immune response. We speculate sCD83 may be a critical factor in the process of PRRSV-coordinated macrophage polarization. In this study, we found that PAMs co-cultured with PRRSV-infected MoDCs inhibited the M1 macrophage while enhancing the M2 macrophage. This was accompanied by a decrease in the pro-inflammatory cytokine TNF-α and iNOS and an increase in the anti-inflammatory cytokine IL-10 and Arg1. Meanwhile, sCD83 incubation causes the same specific effects lead to a switch in macrophage from M1 to M2. Neutralization of sCD83 removes the inhibitory effects of PRRSV on PAMs. Using reverse genetics, we generated recombinant PRRSVs with mutations in N protein, nsp1α, and nsp10 (knockout sCD83-concerned key amino acid site). Four mutant viruses lost the suppression of M1 macrophage markers, in contrast to the restriction of the upregulation of M2 macrophage markers. These findings suggest that PRRSV modulates the switch of macrophage polarization from M1 to M2 by upregulating the MoDC-induced secretion of CD83, providing new insights into the mechanism by which PRRSV regulates host immunity.

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Ishibashi, Mariko, Ryosuke Kinoshita, Koiti Inokuchi, Hiroshi Handa, Makoto Sasaki, Norio Komatsu, Yoichi Imai et al. "Serum Soluble CD86, Still a Prognostic Factor in the Novel Agent Era in Multiple Myeloma Patients, Is Produced By Myeloma Cells with High CD86 Variant 3 Expression". Blood 134, Supplement_1 (13 novembre 2019): 4361. http://dx.doi.org/10.1182/blood-2019-124635.

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Introduction: We previously reported that CD86 expressed on tumor cells from multiple myeloma (MM) patients is associated with a proliferative advantage of tumor cells and suppresses the antitumor immune response by inducing the immunosuppressive cytokine IL-10 from CD4+ T cells via CD86-CD28 interaction [Yamashita T, Clin Cancer Res 2009]. Furthermore, CD28 expressed on MM cells can mediate pro-survival signaling through CD86-CD28 interaction, resulting in chemotherapeutic resistance [Murray ME, Blood 2014]. Hock et al. reported that serum soluble CD86 levels (sCD86) were a significant independent prognostic marker in MM patients treated with conventional chemotherapy [Br J Haematol 2006]. However, it is unknown whether serum soluble CD86 is still a prognostic marker in the novel agent era and how sCD86 is produced in serum. In this study, we investigated the association of clinical characteristics and prognosis with serum sCD86 and elucidated the mechanism by which sCD86 is produced in MM patients. Materials and Methods: 1) Peripheral blood and bone marrow (BM) samples were obtained from 294 newly diagnosed (42 asymptomatic and 252 symptomatic) MM patients, 16 patients with monoclonal gammopathy of undetermined significance (MGUS), and 16 healthy controls. 2) sCD86 levels were measured using ELISA. 3) The expression of cell-surface antigen on plasma cells identified as CD138-positive and CD38-strong positive cells were analyzed using flow cytometry. Expression of the CD86 full-length (variant 1) and alternatively spliced variant deleting exon 6 (variant 3), which encodes for the transmembrane domain, in MM cell lines and CD138+ plasma cells isolated from BM samples from MM patients were analyzed using real-time PCR. Results: 1) sCD86 levels were significantly increased in MM patients compared with MGUS patients and healthy controls. Among MM patients, the levels were significantly higher in symptomatic than in asymptomatic patients and markedly increased in advanced stages (International Staging System [ISS] stage II/III and revised ISS II/III). We next investigated the differences in clinical characteristics between two groups according to serum sCD86 levels: high (≥2.16 ng/mL); and low (<2.16 ng/mL). In the high group, plasma cell percentages and corrected calcium, creatinine, and β2-microglobulin levels were markedly higher, and hemoglobin, hematocrit, and estimated glomerular filtration rate significantly lower than those in the low group. Furthermore, MM patients in the high group had significantly shorter overall survival (OS) times than those in the low group (hazard ratio, 0.385; 95% confidence interval, 0.1572-0.9425; P=0.032). 2) CD86 variant 1 and variant 3 were found to be expressed in plasma cells from MM patients. The mRNA levels of CD86 variant 3 in the sCD86-high group were significantly increased in comparison with the low group. These levels were significantly correlated with the concentration of sCD86 (r=0.635, P=0.0003). High levels of CD86 variant 3 mRNA were detected in primary MM cells, but not in hematopoietic BM cells, although the expression of CD86 variant 1 was the same in both MM and hematopoietic cells. On the other hand, sCD86 in cell cultures and mRNA of CD86 variant 3 were not detected in CD86-expressing MM cell lines, suggesting that these phenomena may be seen only in primary MM cells from patients. 3) There was a weak positive correlation between serum sCD86 concentration and CD86 expression levels on MM cells. However, progression-free survival (PFS) and OS were not significantly different between MM patients with high and low expression of CD86. Further, we confirmed that recombinant human CD86 could bind to MM cell lines through CD86-CD28 interaction, which might induce aggressive disease with chemotherapeutic resistance in MM cells. Consistent with this hypothesis, patients with low expression of sCD86/its receptor CD28 had longer OS times than others. In addition, receptor CD28 expression in patients with high CD86 expression was significantly higher than in those with low expression levels. Conclusions: We demonstrated that sCD86 is produced via expression of CD86 variant 3 in primary MM cells and that sCD86 is a prognostic marker in the novel agent era. These results suggest that serum sCD86 levels may reflect disease progression through CD28 expressed on myeloma cells and be a useful prognostic factor. Disclosures Inokuchi: Novartis: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria. Handa:Ono: Research Funding. Komatsu:Fuso Pharmaceutical Industries, Ltd.: Research Funding; Novartis K.K: Speakers Bureau; Pharma Essentia: Research Funding, Speakers Bureau; Wako Pure Chemical Industries, Ltd.: Research Funding; Takeda Pharmaceutical Company Limited: Research Funding, Speakers Bureau. Imai:Celgene: Honoraria, Research Funding; Janssen Parmaceutical K.K.: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding. Ito:Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Ono: Honoraria. Tamura:Celegene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Ono Pharmaceutical: Honoraria; Takeda Pharmaceutical: Honoraria.

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Muñiz, Carmen, Lourdes Martín-Martín, Antonio López, Blanca Sánchez-González, Antonio Salar, Julia Almeida, Juan-Manuel Sancho et al. "Contribution of cerebrospinal fluid sCD19 levels to the detection of CNS lymphoma and its impact on disease outcome". Blood 123, n. 12 (20 marzo 2014): 1864–69. http://dx.doi.org/10.1182/blood-2013-11-537993.

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Key Points Increased levels of sCD19 protein in the CSF are associated with CNS disease in DLBCL and BL patients at risk of CNS lymphoma. Presence of lymphoma cells by FCM and/or increased CSF sCD19 levels are related with a poorer EFS and/or OS in DLBCL and BL patients.

19

Ho, AD, M. Grossman, L. Trumper, A. Pezzutto, H. Pralle, S. Boedewadt-Radzun, U. Papendick, B. God, T. Zwingers e W. Hunstein. "Clinical implications of increased plasma levels of CD8 in patients with hairy cell leukemia". Blood 75, n. 5 (1 marzo 1990): 1119–24. http://dx.doi.org/10.1182/blood.v75.5.1119.bloodjournal7551119.

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Plasma levels of soluble T-suppressor/cytotoxic antigen (sCD8) were measured at diagnosis or before systemic treatment in 69 patients with hairy cell leukemia (HCL). The 49 nonsplenectomized patients were characterized by high concentrations of sCD8 antigen as compared with 17 controls (P less than .0001). The median sCD8 level in non- splenectomized patients was 1,050 U/mL (range: 160 to 2,400 U/mL) and was significantly higher (P less than .0001) than the median of 275 U/mL (range: 20 to 1,080 U/mL) in splenectomized patients. The relationship of sCD8 to clinical response to subsequent interferon alpha (IFN alpha) treatment was analyzed. Patients who showed subsequent hematologic response with normalization of all blood counts had significantly lower levels of sCD8 concentrations at diagnosis than those who did not (P = .0056). Furthermore, normalization of sCD8 during IFN alpha treatment paralleled the achievement of normal counts in peripheral blood, whereas soluble interleukin-2 receptor (sIL-2R) levels remained high in most patients after 12 to 15 months of treatment. We speculate that activation of suppressor/cytotoxic T cells might play a role in myelosuppression, and its modulation during treatment with IFN alpha correlates with normalization in peripheral blood counts.

20

Ho, AD, M. Grossman, L. Trumper, A. Pezzutto, H. Pralle, S. Boedewadt-Radzun, U. Papendick, B. God, T. Zwingers e W. Hunstein. "Clinical implications of increased plasma levels of CD8 in patients with hairy cell leukemia". Blood 75, n. 5 (1 marzo 1990): 1119–24. http://dx.doi.org/10.1182/blood.v75.5.1119.1119.

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Abstract Plasma levels of soluble T-suppressor/cytotoxic antigen (sCD8) were measured at diagnosis or before systemic treatment in 69 patients with hairy cell leukemia (HCL). The 49 nonsplenectomized patients were characterized by high concentrations of sCD8 antigen as compared with 17 controls (P less than .0001). The median sCD8 level in non- splenectomized patients was 1,050 U/mL (range: 160 to 2,400 U/mL) and was significantly higher (P less than .0001) than the median of 275 U/mL (range: 20 to 1,080 U/mL) in splenectomized patients. The relationship of sCD8 to clinical response to subsequent interferon alpha (IFN alpha) treatment was analyzed. Patients who showed subsequent hematologic response with normalization of all blood counts had significantly lower levels of sCD8 concentrations at diagnosis than those who did not (P = .0056). Furthermore, normalization of sCD8 during IFN alpha treatment paralleled the achievement of normal counts in peripheral blood, whereas soluble interleukin-2 receptor (sIL-2R) levels remained high in most patients after 12 to 15 months of treatment. We speculate that activation of suppressor/cytotoxic T cells might play a role in myelosuppression, and its modulation during treatment with IFN alpha correlates with normalization in peripheral blood counts.

21

Lundell, Anna-Carin, Kerstin Andersson, Elisabet Josefsson, Alexander Steinkasserer e Anna Rudin. "Soluble CD14 and CD83 from Human Neonatal Antigen-Presenting Cells Are Inducible by Commensal Bacteria and Suppress Allergen-Induced Human Neonatal Th2 Differentiation". Infection and Immunity 75, n. 8 (25 maggio 2007): 4097–104. http://dx.doi.org/10.1128/iai.01744-06.

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ABSTRACT CD14 is expressed on the cell surface of various antigen-presenting cells, and CD83 is a maturation marker for dendritic cells (DC). CD14 and CD83 are also present as soluble proteins, and both have immunoregulatory functions. We examined whether neonatal cord blood monocytes or DC released soluble CD14 (sCD14) or sCD83 when exposed to the commensal intestinal bacteria Clostridium perfringens, Staphylococcus aureus, Lactobacillus rhamnosus, Escherichia coli, and Bacteroides fragilis. We found that the gram-positive bacteria C. perfringens and S. aureus, but not gram-negative bacteria, induced the release of sCD14 from monocytes. DC, on the other hand, released sCD14 in response to both gram-positive and gram-negative bacteria. Moreover, the expression of the virulence factor staphylococcal protein A seemed to be important for S. aureus-induced sCD14 production from both monocytes and DC. Soluble CD83 was released from DC, but not from monocytes, when exposed to both gram-positive and gram-negative bacteria. Finally, to investigate whether sCD14 or sCD83 could modulate neonatal allergen-induced T-cell differentiation, DC were exposed to birch allergen alone or in the presence of sCD14 or sCD83 and then cocultured with autologous T cells. We demonstrate that sCD14 and sCD83 inhibited the birch allergen-induced Th2 differentiation by suppressing interleukin 13 production. Together, these results suggest that the commensal intestinal flora may be an important stimulus for the developing immune system by inducing the immunoregulatory proteins sCD14 and sCD83, which may be involved in preventing T-cell sensitization to allergens in infants.

22

Kogure, T., T. Itoh, Y. Shimada, T. Shintani, H. Ochiai e K. Terasawa. "Detection of serum soluble markers of immune activation in rheumatoid arthritis". Mediators of Inflammation 5, n. 4 (1996): 262–65. http://dx.doi.org/10.1155/s0962935196000373.

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The mutual correlation among soluble CD4 (sCD4), soluble CD8 (sCD8), and soluble CD23 (sCD23) has not yet been studied in patients with rheumatoid arthritis (RA), although previous studies have demonstrated that certain soluble markers of immune activation are elevated in RA. Thus, we examined this correlation based on the serum levels of sCD4, sCD8 and sCD23, and that of their levels with other serum markers such as immunoglobulin (Ig) subtypes (IgG, IgM and IgA), IgM-rheumatoid factor (IgM-RF) and C-reactive protein (CRP) in 25 RA patients, sCD4 was not elevated, whereas both sCD8 and sCD23 increased in RA patients compared with the healthy controls; a majority of RA patients, in particular, showed a high sCD23 level. The level of sCD23 showed a correlation with that of IgM-RF, but not with those of IgG, IgM, IgA and CRP. Importantly, a high level of sCD23 was not always accompartied with that of sCD8. The independent change between sCD23 and sCD8 levels was also observed in a one-year follow-up study of the two RA patients. These findings indicate that B cells might be generally activated in RA, whereas T-cell activation in variable in each patient with RA, suggesting that sCD23 is a more indicative marker for the immune status of RA patients than sCD8 from the clinical aspects.

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Olszewski, Jurek, Wiesław Chudzik, Kazimierz Wiśniewski, Jarosław Miłonski e Robert Matyja. "An Assessment of Concentrations of Soluble CD4 and CD8 Receptors in Serum before and after Surgical Treatment in Patients with Chronic Maxillary Sinusitis". American Journal of Rhinology 17, n. 3 (maggio 2003): 123–26. http://dx.doi.org/10.1177/194589240301700301.

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Background The aim of this study was to assess the concentrations of soluble CD4 (sCD4) and sCD8 receptors in serum of patients before and after surgical treatment of chronic maxillary sinusitis. Methods We examined 57 patients, aged 20–63 years (mean age, 41 ± 0.5 years), and divided them into four groups: group I, 14 patients with chronic maxillary sinusitis without allergy; group II, 15 patients with chronic maxillary sinusitis with allergy; group III, 16 patients with cyst of maxillary sinuses without allergy (control); and group IV, 12 patients with cyst of maxillary sinuses with allergy (control). The assay of sCD4 and sCD8 receptor concentrations was performed by means of enzyme-linked immunosorbent assay method. The concentrations of sCD4 and sCD8 receptors before and after 30 days of surgical treatment of maxillary sinuses were examined. Results In our studies the increase of concentration of sCD4 in groups I and II in comparison with the concentration in control groups were statistically significant. The differences between mean concentrations of sCD8 in groups I and II and in the control groups were not statistically significant. After surgical treatment of chronic maxillary sinusitis, a significant decrease in values of sCD4 and sCD8 in comparison with the results before surgical treatment suggest that the measurement of cell suppression product concentration can be used to assess the extirpation of the inflammatory process and the effectiveness of the operation method. Conclusion Changes in concentration of sCD4 and sCD8 manifest activation or suppression of cells with particular receptor expression.

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Peckert-Maier, Katrin, Dmytro Royzman, Pia Langguth, Anita Marosan, Astrid Strack, Atefeh Sadeghi Shermeh, Alexander Steinkasserer, Elisabeth Zinser e Andreas B. Wild. "Tilting the Balance: Therapeutic Prospects of CD83 as a Checkpoint Molecule Controlling Resolution of Inflammation". International Journal of Molecular Sciences 23, n. 2 (10 gennaio 2022): 732. http://dx.doi.org/10.3390/ijms23020732.

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Chronic inflammatory diseases and transplant rejection represent major challenges for modern health care. Thus, identification of immune checkpoints that contribute to resolution of inflammation is key to developing novel therapeutic agents for those conditions. In recent years, the CD83 (cluster of differentiation 83) protein has emerged as an interesting potential candidate for such a “pro-resolution” therapy. This molecule occurs in a membrane-bound and a soluble isoform (mCD83 and sCD83, respectively), both of which are involved in resolution of inflammation. Originally described as a maturation marker on dendritic cells (DCs), mCD83 is also expressed by activated B and T cells as well as regulatory T cells (Tregs) and controls turnover of MHC II molecules in the thymus, and thereby positive selection of CD4+ T cells. Additionally, it serves to confine overshooting (auto-)immune responses. Consequently, animals with a conditional deletion of CD83 in DCs or regulatory T cells suffer from impaired resolution of inflammation. Pro-resolving effects of sCD83 became evident in pre-clinical autoimmune and transplantation models, where application of sCD83 reduced disease symptoms and enhanced allograft survival, respectively. Here, we summarize recent advances regarding CD83-mediated resolution of inflammatory responses, its binding partners as well as induced signaling pathways, and emphasize its therapeutic potential for future clinical trials.

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Kubysheva, Nailya, Larisa Postnikova, Svetlana Soodaeva, Viкtor Novikov, Tatyana Eliseeva, Ildar Batyrshin, Timur Li, Igor Klimanov e Alexander Chuchalin. "Relationship of the Content of Systemic and Endobronchial Soluble Molecules of CD25, CD38, CD8, and HLA-I-CD8 and Lung Function Parameters in COPD Patients". Disease Markers 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/8216723.

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The definition of new markers of local and systemic inflammation of chronic obstructive pulmonary disease (COPD) is one of the priority directions in the study of pathogenesis and diagnostic methods improvement for this disease. We investigated 91 patients with COPD and 21 healthy nonsmokers. The levels of soluble CD25, CD38, CD8, and HLA-I-CD8 molecules in the blood serum and exhaled breath condensate (EBC) in moderate-to-severe COPD patients during exacerbation and stable phase were studied. An unidirectional change in the content of sCD25, sCD38, and sCD8 molecules with increasing severity of COPD was detected. The correlations between the parameters of lung function and sCD8, sCD25, and sHLA-I-CD8 levels in the blood serum and EBC were discovered in patients with severe COPD. The findings suggest a pathogenetic role of the investigated soluble molecules of the COPD development and allow considering the content of sCD8, sCD25, and sHLA-I-CD8 molecules as additional novel systemic and endobronchial markers of the progression of chronic inflammation of this disease.

26

Yin, Xin-Ke, Chao Wang, Li-Li Feng, Shao-Mei Bai, Wei-Xing Feng, Neng-Tai Ouyang, Zhong-Hua Chu, Xin-Juan Fan e Qi-Yuan Qin. "Expression Pattern and Prognostic Value of CTLA-4, CD86, and Tumor-Infiltrating Lymphocytes in Rectal Cancer after Neoadjuvant Chemo(radio)therapy". Cancers 14, n. 22 (14 novembre 2022): 5573. http://dx.doi.org/10.3390/cancers14225573.

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The synergistic effect of combining immune checkpoint inhibitors (ICIs) with neoadjuvant chemo(radio)therapy (nCRT) in colorectal cancer is still limited. We aimed to understand the impact of nCRT on the tumor microenvironment and to explore favorable immune markers of this combination. Herein, we investigated the expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), CD86, CD4, and CD8 after nCRT and its association with clinicopathological characteristics. Immunostaining of immune-related molecules was performed in 255 surgically resected specimens from rectal cancer patients treated with nCRT. CD4 and CD8 expression on the tumor (tCD4/CD8), stroma (sCD4/CD8), and invasive front (iCD4/CD8) was evaluated. The expression levels of immune-related molecules were significantly lower in the nCRT-treated group, except for CTLA-4 and sCD8. However, patients with higher sCD8+ cell density and CTLA-4 expression had better progression-free survival (PFS) and distant metastasis-free survival (DMFS). In addition, higher CD86 expression was associated with poorer overall survival (OS). Higher CTLA-4 expression was associated with higher tCD8+ cell density, whereas CD86 expression was correlated with the cell density of t/sCD8. Prognostic analysis confirmed that the relationships between CTLA-4 and DMFS as well as CD86 and OS were significantly correlated in low rather than high CD8+ cell density. Further the combination of CD8+ cell density and CD86 expression was shown to be an independent prognostic factor of OS, whereas the combination of CTLA-4 was not for DMFS. Together, these results demonstrate significant correlations between CD86 expression and t/sCD8+ cell density in rectal cancer after nCRT and could potentially have clinical implications for combining ICIs and nCRT.

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Moretti, Edgardo, Beatriz Basso, Liliana Cervetta, Ana Brigada e Gustavo Barbieri. "Patterns of Cytokines and Soluble Cellular Receptors in the Sera of Children with Acute Chagas' Disease". Clinical and Vaccine Immunology 9, n. 6 (novembre 2002): 1324–27. http://dx.doi.org/10.1128/cdli.9.6.1324-1327.2002.

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ABSTRACT Cytokines and soluble cellular receptors are involved in inflammatory processes and probably in the pathogenesis of parasite and bacterial diseases. In a previous study, we reported increased levels of soluble receptors of interleukin-2 (sIL2-R) in children with acute Chagas' disease, one of the main parasitic infections that is endemic in Latin America. We sought to analyze the pattern of different cytokines and soluble receptors in the sera of children with chagasic infection. Children with acute and indeterminate stages of Chagas' disease, as well as nonchagasic children, were studied. Sera were assayed by enzyme-linked immunosorbent assay to measure the levels of tumor necrosis factor alpha (TNF-α), IL-6, IL-2, IL-8, IL-12, sIL-2R, and the soluble receptors of CD8 and CD4 (sCD8 and sCD4). sIL-2R and sCD8 showed the highest levels in serum in acutely infected children, decreasing after specific antiparasite therapy. Chronic children showed a pattern similar to the one of nonchagasic children. Although they were not statistically significant, TNF-α, IL-6, and sCD4 showed a tendency to reach high levels in the acutely infected group, whereas IL-2, IL-8, and IL-12 did not reveal changes with respect to the noninfected children. In summary, we report here the patterns of cytokines and soluble receptors in in the sera of children infected with Trypanosoma cruzi; we found significantly increased levels of sIL-2R and sCD8 in acute infection that decreased after therapy, and high levels of TNF-α, IL-6, and sCD4 in some of the acute patients. The measurement of sIL-2R and sCD8 may provide a useful tool in the follow-up of children with Chagas' disease.

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Jiang, Chun-Xuan. "THE PRIME PRINCIPLE IN CLUSTERS AND NANOSTRUCTURES". Algebras Groups and Geometries 39, n. 2 (1 dicembre 2023): 189–95. http://dx.doi.org/10.29083/agg.39.02.2023/sc189.

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Ho, AD, M. Maruyama, A. Maghazachi, JR Mason, S. Gluck e RE Corringham. "Soluble CD4, soluble CD8, soluble CD25, lymphopoieitic recovery, and endogenous cytokines after high-dose chemotherapy and blood stem cell transplantation". Blood 84, n. 10 (15 novembre 1994): 3550–57. http://dx.doi.org/10.1182/blood.v84.10.3550.3550.

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Abstract Mononuclear cell preparations from peripheral blood after mobilization with hematopoietic growth factors have been shown to induce accelerated neutrophil and platelet recovery as compared with that induced by autologous bone marrow transplantation after myeloablative chemotherapy. Because these mononuclear cell products contain many immunocompetent cells other than hematopoietic progenitors, these accessory cells might contribute to the rapid immunohematopoietic reconstitution. We have monitored the concentrations of soluble CD4 (sCD4), sCD8, and sCD25; the recovery of the lymphocyte subsets and of natural killer (NK) cells; and the endogenous levels of granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3), IL-6, and granulocyte-macrophage-CSF (GM-CSF) in 12 patients who underwent high- dose chemotherapy supported by blood stem cells that were obtained by mobilization with chemotherapy and GM-CSF. The concentrations of both G- CSF and IL-6 peaked at 7 days after reinfusion of stem cells, and this transient elevation preceded the increase in the white blood cell count by approximately 5 to 7 days. The levels of sCD4 and sCD8 increased to a maximum on day 21, and the time to peak levels coincided with the maximum increase in white blood cell count, absolute neutrophil count, or lymphocytes. The levels of sCD25 were found to be elevated from day 7 to day 21. Statistically, the increases in sCD4, sCD8, sCD25, G-CSF, and IL-6 were highly significant, whereas there were no significant changes in IL-3 and GM-CSF. A rapid recovery of the NK activity was found in all 8 of the patients who could be monitored for this assay. Therefore, our study suggests that recovery of CD4+ cells, CD8+ cells, and NK activity coincided with that of neutrophils, which is preceded by a marked, but transient, elevation of IL-6 and G-CSF.

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Ho, AD, M. Maruyama, A. Maghazachi, JR Mason, S. Gluck e RE Corringham. "Soluble CD4, soluble CD8, soluble CD25, lymphopoieitic recovery, and endogenous cytokines after high-dose chemotherapy and blood stem cell transplantation". Blood 84, n. 10 (15 novembre 1994): 3550–57. http://dx.doi.org/10.1182/blood.v84.10.3550.bloodjournal84103550.

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Abstract (sommario):

Mononuclear cell preparations from peripheral blood after mobilization with hematopoietic growth factors have been shown to induce accelerated neutrophil and platelet recovery as compared with that induced by autologous bone marrow transplantation after myeloablative chemotherapy. Because these mononuclear cell products contain many immunocompetent cells other than hematopoietic progenitors, these accessory cells might contribute to the rapid immunohematopoietic reconstitution. We have monitored the concentrations of soluble CD4 (sCD4), sCD8, and sCD25; the recovery of the lymphocyte subsets and of natural killer (NK) cells; and the endogenous levels of granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3), IL-6, and granulocyte-macrophage-CSF (GM-CSF) in 12 patients who underwent high- dose chemotherapy supported by blood stem cells that were obtained by mobilization with chemotherapy and GM-CSF. The concentrations of both G- CSF and IL-6 peaked at 7 days after reinfusion of stem cells, and this transient elevation preceded the increase in the white blood cell count by approximately 5 to 7 days. The levels of sCD4 and sCD8 increased to a maximum on day 21, and the time to peak levels coincided with the maximum increase in white blood cell count, absolute neutrophil count, or lymphocytes. The levels of sCD25 were found to be elevated from day 7 to day 21. Statistically, the increases in sCD4, sCD8, sCD25, G-CSF, and IL-6 were highly significant, whereas there were no significant changes in IL-3 and GM-CSF. A rapid recovery of the NK activity was found in all 8 of the patients who could be monitored for this assay. Therefore, our study suggests that recovery of CD4+ cells, CD8+ cells, and NK activity coincided with that of neutrophils, which is preceded by a marked, but transient, elevation of IL-6 and G-CSF.

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Ho, AD, R. Haas, G. Wulf, W. Knauf, R. Ehrhardt, B. Heilig, M. Korbling, G. Schulz e W. Hunstein. "Activation of lymphocytes induced by recombinant human granulocyte- macrophage colony-stimulating factor in patients with malignant lymphoma". Blood 75, n. 1 (1 gennaio 1990): 203–12. http://dx.doi.org/10.1182/blood.v75.1.203.203.

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Abstract To investigate effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on lymphoid cells in vivo, we monitored changes in absolute lymphocyte counts, plasma concentrations of soluble interleukin-2 receptor (sIL-2R) and soluble cytotoxic/suppressor (sCD8) antigens, and phenotypic changes of surface membrane antigens of peripheral mononuclear cells from 14 patients with malignant lymphoma treated with rhGM-CSF. Eight of the 14 patients had relapsed or had refractory non-Hodgkin's lymphoma (NHL) and received rhGM-CSF after intensive chemotherapy with novantrone (NO) and high- dose Ara-C (AC) (NOAC) as salvage regimen. Six other patients with NHL or Hodgkin's disease (HD) were in complete remission and treated with rhGM-CSF to enhance peripheral hematopoietic progenitor cell harvest for autografting. An increase in absolute lymphocyte count at the zenith of leukocyte elevation and a drastic increase in concentration of sIL-2R from a median of 565 U/mL to 6,700 U/mL on rhGM-CSF infusion were found in all patients. There was also a moderate increase in sCD8 levels from a median of 277 U/mL to 470 U/mL. Ten patients were available for serial studies of phenotypic changes in surface membrane antigens. A significant increase in CD25+ (IL-2R+) (P = .0020) and CD4+ (P = .0137) lymphocytes was observed in all patients, but no significant change in CD3+, CD8+, TCR delta 1+, or CD19+ cells. Elevations in absolute lymphocyte counts or in concentrations of sIL-2R or sCD8 were not observed in four other patients during recovery from intensive chemotherapy without rhGM-CSF support. Our results provide evidence that administration of rhGM-CSF might activate lymphocytes in vivo. The impact of this activation on the remission rate and duration, as well as survival in patients with NHL, warrants further investigation.

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Ho, AD, R. Haas, G. Wulf, W. Knauf, R. Ehrhardt, B. Heilig, M. Korbling, G. Schulz e W. Hunstein. "Activation of lymphocytes induced by recombinant human granulocyte- macrophage colony-stimulating factor in patients with malignant lymphoma". Blood 75, n. 1 (1 gennaio 1990): 203–12. http://dx.doi.org/10.1182/blood.v75.1.203.bloodjournal751203.

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Abstract (sommario):

To investigate effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on lymphoid cells in vivo, we monitored changes in absolute lymphocyte counts, plasma concentrations of soluble interleukin-2 receptor (sIL-2R) and soluble cytotoxic/suppressor (sCD8) antigens, and phenotypic changes of surface membrane antigens of peripheral mononuclear cells from 14 patients with malignant lymphoma treated with rhGM-CSF. Eight of the 14 patients had relapsed or had refractory non-Hodgkin's lymphoma (NHL) and received rhGM-CSF after intensive chemotherapy with novantrone (NO) and high- dose Ara-C (AC) (NOAC) as salvage regimen. Six other patients with NHL or Hodgkin's disease (HD) were in complete remission and treated with rhGM-CSF to enhance peripheral hematopoietic progenitor cell harvest for autografting. An increase in absolute lymphocyte count at the zenith of leukocyte elevation and a drastic increase in concentration of sIL-2R from a median of 565 U/mL to 6,700 U/mL on rhGM-CSF infusion were found in all patients. There was also a moderate increase in sCD8 levels from a median of 277 U/mL to 470 U/mL. Ten patients were available for serial studies of phenotypic changes in surface membrane antigens. A significant increase in CD25+ (IL-2R+) (P = .0020) and CD4+ (P = .0137) lymphocytes was observed in all patients, but no significant change in CD3+, CD8+, TCR delta 1+, or CD19+ cells. Elevations in absolute lymphocyte counts or in concentrations of sIL-2R or sCD8 were not observed in four other patients during recovery from intensive chemotherapy without rhGM-CSF support. Our results provide evidence that administration of rhGM-CSF might activate lymphocytes in vivo. The impact of this activation on the remission rate and duration, as well as survival in patients with NHL, warrants further investigation.

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Putz, D., U. Barnas, A. Luger, G. Mayer, W. Woloszczuk e H. Graf. "Biocompatibility of High-Flux Membranes". International Journal of Artificial Organs 15, n. 8 (agosto 1992): 456–60. http://dx.doi.org/10.1177/039139889201500802.

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Standard dialysis with cuprophane membranes is known to stimulate the immune system. As a result of activation of macrophages various interleukins and tumor necrosis factor (TNF) are secreted, presenting further evidence of the poor biocompatibility of cuprophane. We investigated the immunogenic properties of three modern high-flux membranes. Seven patients were studied during hemodiafiltration sessions using either a polysulfone (F60, Fresenius), a polymethylmetacrylate (BK 2.1, Toray) or a cellulose triacetate (FB-210 U, Nipro) dialyzer in a hemodiafiltration procedure. Serial measurements were made during each treatment of interleukin-1β (II-1β), TNF, soluble IL-2 receptor (sII-2r), soluble CD4 (sCD4), soluble CD8 (sCD8), interferon gamma (IFNg) and neopterin. In contrast to the known increase of IL-1β, IL-2r and TNF with cuprophane membranes, none of the modern high-flux dialyzers stimulated the production of these factors. Significant decreases of neopterin and sCD4 were observed. IFNg and sCD8 did not change significantly. Our results suggest that the modern high-flux dialyzers are non-immunogenic, and thus provide further evidence of the superior biocompatibility of synthetic or semisynthetic membranes over the conventional cuprophane.

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Hamed, Nahla, Nahla Farahat, Manal El Sorady, Dalia Nafee e Sherine Barakat. "Clinical significance of sCD86 levels in patients with acute myelogenous leukemia". Alexandria Journal of Medicine 47, n. 1 (1 marzo 2011): 25–30. http://dx.doi.org/10.1016/j.ajme.2011.04.002.

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35

Nascimento, Catarina, Andreia Gameiro, Jorge Correia, João Ferreira e Fernando Ferreira. "The Landscape of Tumor-Infiltrating Immune Cells in Feline Mammary Carcinoma: Pathological and Clinical Implications". Cells 11, n. 16 (18 agosto 2022): 2578. http://dx.doi.org/10.3390/cells11162578.

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Feline mammary carcinoma (FMC) shares key molecular and clinicopathological features with human breast cancer. We have herein studied the inflammatory infiltrate of FMC in order to uncover potential therapeutic targets and prognostic markers. To this end, the expression of different markers (CD3, CD4, CD8, CD20, CD56, FoxP3, CD68 and CD163) was analyzed in total, stromal (s) and intratumoral (i) tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs), in 73 feline mammary carcinomas. The results revealed that higher percentages of sCD8+ TILs were associated with longer disease-free survival (p = 0.05) and overall survival (p = 0.021). Additionally, higher percentages of iCD4+ TILs correlated with positive lymph node status (p = 0.003), whereas CD163+ TAMs were associated with undifferentiated tumors (p = 0.013). In addition, sCD3+ (p = 0.033), sCD8+ (p = 0.044) and sCD68+ (p = 0.023) immune cells were enriched in triple negative normal-like carcinomas compared to other subtypes. Altogether, our results suggest that specific subsets of immune cells may play a major role in clinical outcome of cats with mammary carcinoma, resembling what has been reported in human breast cancer. These data further support the relevance of the feline model in breast cancer studies.

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Kashchenko, Mikhail. "INTERPRETATION OF THE MECHANISM OF THE INFLUENCE OF π0- MESONS ON THE PROCESS OF ATTRACTION OF NUCLEI". Hadronic Journal 47, n. 1 (1 marzo 2024): 89–94. http://dx.doi.org/10.29083/hj.47.01.2024/sc89.

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37

Díaz García, Elena, Sara García-Tovar, Enrique Alfaro, Ester Zamarrón, Alberto Mangas, Raúl Galera, José Juan Ruíz Hernández et al. "Role of CD39 in COVID-19 Severity: Dysregulation of Purinergic Signaling and Thromboinflammation". IBJ Plus 1, s5 (3 giugno 2022): 1. http://dx.doi.org/10.24217/2531-0151.22v1s5.00001.

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CD39/NTPDase1 has emerged as an important molecule that contributes to maintain inflammatory and coagulatory homeostasis. Various studies have hypothesized the possible role of CD39 in COVID-19 pathophysiology since no confirmatory data shed light in this regard. Therefore, we aimed to quantify CD39 expression on COVID-19 patients exploring its association with severity clinical parameters and ICU admission, while unraveling the role of purinergic signaling on thromboinflammation in COVID-19 patients. We selected a prospective cohort of patients hospitalized due to severe COVID-19 pneumonia (n=75), a historical cohort of Influenza A pneumonia patients (n=18) and sex/age-matched healthy controls (n=30). CD39 was overexpressed in COVID-19 patients' plasma and immune cell subsets and related to hypoxemia. Plasma soluble form of CD39 (sCD39) was related to length of hospital stay and independently associated with intensive care unit admission (adjusted odds ratio 1.04, 95%CI 1.0-1.08, p=0.038), with a net reclassification index of 0.229 (0.118-0.287; p=0.036). COVID-19 patients showed extracellular accumulation of adenosine nucleotides (ATP and ADP), resulting in systemic inflammation and pro-coagulant state, as a consequence of purinergic pathway dysregulation. Interestingly, we found that COVID-19 plasma caused platelet activation, which was successfully blocked by the P2Y12 receptor inhibitor, ticagrelor. Therefore, sCD39 is suggested as a promising biomarker for COVID-19 severity. As a conclusion, our study indicates that CD39 overexpression in COVID-19 patients could be indicating purinergic signaling dysregulation, which might be at the basis of COVID-19 thromboinflammation disorder

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Barlan, Işil B., M. M. Başaran, M. Bakir, F. Tükenmez e Nural Bekiroğlu. "Serum TNF-α, sCD8 and sIL-2R levels in childhood tuberculosis". Infection 23, n. 4 (luglio 1995): 237–39. http://dx.doi.org/10.1007/bf01781205.

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39

Pujalte, J. M. "Présence pulmonaire de sCD87 au cours du syndrome de détresse respiratoire aiguë (SDRA)". Revue des Maladies Respiratoires 21, n. 6 (dicembre 2004): 1212. http://dx.doi.org/10.1016/s0761-8425(04)71619-8.

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40

Spathas, Nikolaos, Anna C. Goussia, Georgia-Angeliki Koliou, Helen Gogas, Flora Zagouri, Anna Batistatou, Antonia V. Charchanti et al. "Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy—A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study". Cancers 14, n. 22 (16 novembre 2022): 5635. http://dx.doi.org/10.3390/cancers14225635.

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Tumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the efficacy and safety, we report the results of the translational part of our study. We examined the patients’ tumors for total (t), stromal (s), and intratumoral (i) CD8 lymphocyte density (counts/mm2) on tissue-microarray cores. The impact of CD8+ TILs counts on DFS and OS, and its correlation with breast cancer subtypes and standard clinicopathological parameters, were investigated, along with efficacy and safety data. Among the 928 eligible patients, 627 had available CD8+ data. Of which, 24.9% had a high expression of sCD8, iCD8, and total CD8, which were correlated with higher Ki67, TILs density, ER/PgR negativity, and higher histological grade. The 5year DFS and OS rates were 86.1% and 91.4%, respectively. Patients with high iCD8 and tCD8 had longer DFS and OS compared to those with low counts/mm2 (DFS: HR = 0.58, p = 0.011 and HR = 0.65, p = 0.034 and OS: HR = 0.63, p = 0.043 and HR = 0.58, p = 0.020, respectively). Upon adjustment for clinicopathological parameters, iCD8 and tCD8 retained their favorable prognostic significance for DFS and OS, whereas high sCD8 was only prognostic for DFS. Menopausal status, tumor size, and nodal status retained their prognostic significance in all examined multivariate models. CD8+ TILs, and especially their intratumoral subset, represent a potential favorable prognostic factor in early BC.

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Ozkorucu, Duygu, Nuran Cetin, Nadide Melike Sav e Bilal Yildiz. "Urine and serum ghrelin, sCD80 and sCTLA-4 levels in doxorubicin-induced experimental nephrotic syndrome". International Urology and Nephrology 48, n. 7 (27 febbraio 2016): 1187–96. http://dx.doi.org/10.1007/s11255-016-1249-4.

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Sanders, David E., Mark S. Stave, Leslie S. Perkins e Andrew E. DePristo. "SCT89: a computer code for atomic and molecular scattering from clean and adsorbate covered surfaces". Computer Physics Communications 70, n. 3 (luglio 1992): 579–608. http://dx.doi.org/10.1016/0010-4655(92)90118-i.

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De Rie, MA, IM Zonneveld, L. Witkamp, RA Van Lier, TA Out e JD Bos. "Soluble interleukin-2 receptor (sIL-2R) is a marker of disease activity in psoriasis: a comparison of sIL-2R, sCD27, sCD4, sCD8 and sICAM-1." Acta Dermato-Venereologica 76, n. 5 (1 settembre 1996): 357–60. http://dx.doi.org/10.2340/0001555576357360.

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Psoriasis is a T-cell-mediated inflammatory skin disease which can be treated successfully with immunosuppressive drugs. Our purpose was to evaluate disease activity of psoriasis and the effect of immunosuppressive treatment by monitoring the soluble T-cell products sIL-2R, sCD27, sCD4, sCD8 and sICAM-1. Twenty-two patients were treated orally with escalating dosages of cyclosporin A (n = 17)(3-5 mg/kg/day) or FK506 (n = 5)(0.05-0.15 mg/kg/day). The Psoriasis Area and Severity Index (PASI) was used to monitor clinical activity of psoriasis. Serum samples were analyzed by ELISA. sIL-2R levels showed the highest correlation with psoriasis disease activity (rs = 0.89

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Kuryliszyn-Moskal, A., K. Bemacka e O. Bielecka. "Soluble CD4 (sCD4), CD8 (sCD8) and cytokine levels in rheumatoid arthritis complicated by vasculitis". Immunology Letters 56 (maggio 1997): 321. http://dx.doi.org/10.1016/s0165-2478(97)86296-7.

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45

Kuryliszyn-Moskal, A. "Soluble CD4 (sCD4), CD8 (sCD8) and cytokine levels in rheumatoid arthritis complicated by vasculitis". Immunology Letters 56, n. 1-3 (maggio 1997): 321. http://dx.doi.org/10.1016/s0165-2478(97)88134-5.

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46

Brasoveanu, L. I., E. Fonsatti, A. Visintin, M. Pavlovic, I. Cattarossi, F. Colizzi, A. Gasparollo et al. "Melanoma cells constitutively release an anchor-positive soluble protectin (sCD59) that retains functional activities in complement-mediated cytotoxicity". Melanoma Research 7, Supplement 1 (giugno 1997): S10. http://dx.doi.org/10.1097/00008390-199706001-00034.

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47

Kim, Han-Soo, Dimitrios Degiannis, Jana Raskova e Karel Raska. "Cyclosporine A and prednisolone inhibit lectin- and alloantigen-induced release of sCD8: Correlation with proliferative responses". Clinical Immunology and Immunopathology 60, n. 1 (luglio 1991): 27–39. http://dx.doi.org/10.1016/0090-1229(91)90109-n.

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48

van der Merwe, P. Anton, Dale L. Bodian, Susan Daenke, Peter Linsley e Simon J. Davis. "CD80 (B7-1) Binds Both CD28 and CTLA-4 with a Low Affinity and Very Fast Kinetics". Journal of Experimental Medicine 185, n. 3 (3 febbraio 1997): 393–404. http://dx.doi.org/10.1084/jem.185.3.393.

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The structurally related T cell surface molecules CD28 and CTLA-4 interact with cell surface ligands CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells (APC) and modulate T cell antigen recognition. Preliminary reports have suggested that CD80 binds CTLA-4 and CD28 with affinities (Kd values ∼12 and ∼200 nM, respectively) that are high when compared with other molecular interactions that contribute to T cell–APC recognition. In the present study, we use surface plasmon resonance to measure the affinity and kinetics of CD80 binding to CD28 and CTLA-4. At 37°C, soluble recombinant CD80 bound to CTLA-4 and CD28 with Kd values of 0.42 and 4 μM, respectively. Kinetic analysis indicated that these low affinities were the result of very fast dissociation rate constants (koff); sCD80 dissociated from CD28 and CTLA-4 with koff values of ⩾1.6 and ⩾0.43 s−1, respectively. Such rapid binding kinetics have also been reported for the T cell adhesion molecule CD2 and may be necessary to accommodate dynamic T cell–APC contacts and to facilitate scanning of APC for antigen.

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Caruso, C., G. Candore, D. Cigna, S. Tripi, G. Di Gaetano, G. Migneco, G. Montalto, I. Ruggieri e A. Notarbartolo. "Serum Levels of Soluble IL-2R, CD4 and CD8 in Chronic Active HCV Positive Hepatitis". Mediators of Inflammation 3, n. 3 (1994): 185–87. http://dx.doi.org/10.1155/s0962935194000256.

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The aim of the present study was to compare serum levels of soluble forms of interleukin-2 receptor, CD4 and CD8, released by lymphocytes during activation ofthe immune system, in patients with histologically verified chronic active hepatitis associated to hepatitis C virus infection, with those in healthy subjects. Significantly higher levels of soluble IL-2R and soluble CD8 were found in patients with chronic active hepatitis compared with controls. In contrast no difference was found for soluble CD4 values in the two groups. No correlations were found for both sIL-2R and sCD8 and these two molecules with other parameters of liver function. These results indicate that in these patients there is a general activation of the immune system, but the lack of correlation with parameters of liver function strengthens the suggestion that this activation does not play a role in the pathogenesis of chronic type C hepatitis.

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Martens, A., RAJ Janssen, DTh Sleijfer, AA Heijn, NH Mulder, TH The e L. de Leij. "Early sCD8 plasma levels during subcutaneous rIl-2 therapy in patients with renal cell carcinoma correlate with response". British Journal of Cancer 67, n. 5 (maggio 1993): 1118–21. http://dx.doi.org/10.1038/bjc.1993.205.

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