Littérature scientifique sur le sujet « Autoimmune pancreatitis, biomarker, diagnosis, plasmablasts »

IgG4-related disease is a new disease entity involving IgG4 in its clinical presentation and having 6 characteristic features: (1) systemic involvement; (2) solitary or multiple lesions showing diffuse or localized swelling, masses, nodules, and/or wall thickening on imaging; (3) high serum IgG4 concentration >135 mg/dL; (4) abundant infiltration of lymphoplasmacytes and IgG4-bearing plasma cells; (5) a positive response to corticosteroid therapy; and (6) complications of other IgG4-related diseases. To date, most IgG4-related diseases have been recognized as extrapancreatic lesions of autoimmune pancreatitis. This paper will discuss the utility of IgG4 as a biomarker of IgG4-related diseases, including in the diagnosis of autoimmune pancreatitis and its differentiation from pancreatic cancer, in the prediction of relapse, in the long-term follow-up of patients with autoimmune pancreatitis and normal or elevated IgG4 concentrations, and in patients with autoimmune pancreatitis and extrapancreatic lesions, as well as the role of IgG4 in the pathogenesis of IgG4-related disease.

Abstract IgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder that can affect almost any organ. Common presentations include major salivary and lacrimal gland enlargement, orbital disease, autoimmune pancreatitis, retroperitoneal fibrosis and tubulointerstitial nephritis. The main histopathological features are a dense, polyclonal, lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, storiform fibrosis and obliterative phlebitis. The precise pathogenic mechanisms of IgG4-RD are still unclear. CD4+ T and B cells, including IgG4-expressing plasmablasts, constitute the major inflammatory cell populations and are believed to cause organ damage and tissue fibrosis. The diagnosis of the disease may be challenging and should be based on specific histopathological findings, typical laboratory and radiological aspects and an appropriate clinical context. The first-line treatment of IgG4-RD is based on glucocorticoids, which are usually efficacious. However, B cell depletion induced by rituximab has also been found to induce remission in steroid-resistant disease or has been used as steroid-sparing agent for relapsing disease. This review provides an update on clinical and therapeutic aspects of IgG4-RD.

Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic cancer. Identifying non-invasive markers for their early distinction is of utmost importance to avoid unnecessary surgery or a delay in steroid therapy. Thus, this systematic review was conducted to revisit all current evidence on the clinical utility of different serum biomarkers in diagnosing AIP, distinguishing AIP from pancreatic cancer, and predicting disease course, steroid therapy response, and relapse. A systematic review was performed for articles published up to August 2021 by searching electronic databases such as MEDLINE, Web of Science, and EMBASE. Among 5123 identified records, 92 studies were included in the qualitative synthesis. Apart from immunoglobulin (Ig) G4, which was by far the most studied biomarker, we identified autoantibodies against the following: lactoferrin, carboanhydrase II, plasminogen-binding protein, amylase-α2A, cationic (PRSS1) and anionic (PRSS2) trypsinogens, pancreatic secretory trypsin inhibitor (PSTI/SPINK1), and type IV collagen. The identified novel autoantigens were laminin 511, annexin A11, HSP-10, and prohibitin. Other biomarkers included cytokines, decreased complement levels, circulating immune complexes, N-glycan profile changes, aberrant miRNAs expression, decreased IgA and IgM levels, increased IgE levels and/or peripheral eosinophil count, and changes in apolipoprotein isoforms levels. To our knowledge, this is the first systematic review that addresses biomarkers in AIP. Evolving research has recognized numerous biomarkers that could help elucidate the pathophysiological mechanisms of AIP, bringing us closer to AIP diagnosis and its preoperative distinction from pancreatic cancer.

ObjectiveThis study aimed to explore the clinical characteristics and differential diagnosis of patients with autoimmune pancreatitis (AIP) and pancreatic cancer to prevent misdiagnosis and mistreatment.MethodsThe clinical data of patients with AIP with suspected pancreatic or bile duct malignancy and pancreatic cancer were retrospectively analyzed. The risk factors and the diagnostic value of IgG4 and Tbil levels before treatment for AIP was investigated. Moreover, the imaging features and response to hormone therapy were analyzed.ResultsAIP was commonly observed in men. Compared to patients with pancreatic cancer, the incidence of poor appetite and weight loss and carbohydrate antigen 19-9 (CA19-9) level was lower in patients with AIP, while the immunoglobulin G4 (IgG4) level was higher (p < 0.05). After treatment, the IgG4 and CA19-9 levels in patients with AIP were decreased (p < 0.001). IgG4 level before treatment (OR = 2.452, 95%CI: 1.180–5.096, P = 0.016) and total bilirubin (Tbil) level before treatment (OR = 0.992, 95%CI: 0.985–0.998, P = 0.013) were independent risk factors of AIP. Furthermore, the diagnostic value of IgG4 level before treatment, Tbil level before treatment, IgG4/Tbil before treatment, and a combination of these indicators was high. Moreover, 15 (68.18%) patients with AIP had space-occupying lesions of the pancreas, and 16 (72.73%) had autoimmune cholangitis. Most patients with AIP were sensitive to hormone therapy.ConclusionsThe Tbil and IgG4 levels, imaging findings, and hormone therapy reactivity could differentiate AIP from pancreatic cancer. A combination of IgG4, Tbil, and IgG4/Tbil before treatment might be a promising diagnostic biomarker for AIP.

Abstract Background Multiple tools have been applied to radiomics evaluation, while evidence rating tools for this field are still lacking. This study aims to assess the quality of pancreatitis radiomics research and test the feasibility of the evidence level rating tool. Results Thirty studies were included after a systematic search of pancreatitis radiomics studies until February 28, 2022, via five databases. Twenty-four studies employed radiomics for diagnostic purposes. The mean ± standard deviation of the adherence rate was 38.3 ± 13.3%, 61.3 ± 11.9%, and 37.1 ± 27.2% for the Radiomics Quality Score (RQS), the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist, and the Image Biomarker Standardization Initiative (IBSI) guideline for preprocessing steps, respectively. The median (range) of RQS was 7.0 (− 3.0 to 18.0). The risk of bias and application concerns were mainly related to the index test according to the modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The meta-analysis on differential diagnosis of autoimmune pancreatitis versus pancreatic cancer by CT and mass-forming pancreatitis versus pancreatic cancer by MRI showed diagnostic odds ratios (95% confidence intervals) of, respectively, 189.63 (79.65–451.48) and 135.70 (36.17–509.13), both rated as weak evidence mainly due to the insufficient sample size. Conclusions More research on prognosis of acute pancreatitis is encouraged. The current pancreatitis radiomics studies have insufficient quality and share common scientific disadvantages. The evidence level rating is feasible and necessary for bringing the field of radiomics from preclinical research area to clinical stage.

Abstract Purpose Distal cholangiocarcinoma and pancreatic ductal adenocarcinoma are malignancies with poor prognoses that can be difficult to distinguish preoperatively. Thrombospondin-2 has been proposed as a novel diagnostic biomarker for early pancreatic ductal adenocarcinoma. The aim of the present study was to evaluate thrombospondin-2 as a diagnostic and prognostic biomarker in combination with current biomarker CA 19-9 for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma. Methods Thrombospondin-2 was measured in prospectively collected serum samples from patients who underwent surgery with a histopathological diagnosis of distal cholangiocarcinoma (N = 51), pancreatic ductal adenocarcinoma (N = 52) and benign pancreatic diseases (N = 27) as well as healthy blood donors (N = 52) using an enzyme-linked immunosorbent assay. Results Thrombospondin-2 levels (ng/ml) were similar in distal cholangiocarcinoma 55 (41–77) and pancreatic ductal adenocarcinoma 48 (35–80) (P = 0.221). Thrombospondin-2 + CA 19-9 had an area under the curve of 0.92 (95% CI 0.88–0.97) in differentiating distal cholangiocarcinoma and pancreatic ductal adenocarcinoma from healthy donors which was superior to CA 19-9 alone (P < 0.001). The diagnostic value of adding thrombospondin-2 to CA 19-9 was larger in early disease stages. Thrombospondin-2 did not provide additional value to CA 19-9 in differentiating the benign disease group; however, heterogeneity was notable in the benign cohort. Three of five patients with autoimmune pancreatitis patients had greatly elevated thrombospondin-2 levels. Thrombospondin-2 levels had no correlation with prognoses. Conclusions Serum thrombospondin-2 in combination with CA 19-9 has potential as a biomarker for distal cholangiocarcinoma and pancreatic cancer.