Academic literature on the topic 'Auto-immune blistering diseases'

<p class="abstract"><strong>Background:</strong> Vesiculobullous diseases are mostly immune mediated and diagnosed based on the clinical features, histology and Immunofluorescence. The aim of the study was to identify the immunofluorescence pattern in auto immune vesiculobullous diseases and correlate it with the clinical profile and histology.</p><p class="abstract"><strong>Methods:</strong> Patients attending the dermatology outpatient department in a tertiary hospital with vesiculobullous diseases, suggestive of auto immune aetiology were evaluated clinically. Histopathology and direct immuno-fluorescence were done in all patients.<strong></strong></p><p class="abstract"><strong>Results:</strong> During the one year period from June 2008 to July 2009, 40 patients with vesiculobullous disorders clinically suggestive of auto immune aetiology attended the outpatient department. Out of the 40 patients, 22 (55%) patients were diagnosed to have intraepidermal with female preponderance and 18 patients (45%) sub epidermal blistering diseases. Bullous pemphigoid was the commonest sub epidermal disease, seen in 8 patients.</p><p class="abstract"><strong>Conclusions:</strong> In all cases diagnosed clinically as pemphigus a histological diagnosis of pemphigus was made (100%). The clinical variants of pemphigus could also be diagnosed in all cases histologically (100%). The positive and negative predictive value was 100% in pemphigus group cases. Histology of all patients showed subepidermal bulla (100%). A specific diagnosis could be made in 18 patients with sub epidermal disease (100%). DIF was found to be an invaluable tool in diagnosing different diseases belonging to the sub epidermal group, but it was not of much help in sub classifying variants of pemphigus.</p><p class="abstract"> </p>

Abstract Autoimmune diseases are devastating conditions in which the immune system is directed against the host, leading to life-threatening destruction of organs. Although autoantigens are ill-defined in most autoimmune diseases, this is not the case in the skin. Autoimmune bullous diseases have been extensively studied with detailed characterization of autoantigens, the epitopes that are targeted, and the mechanisms of action that mediate autoimmune tissue destruction. Pemphigus is an autoimmune bullous disease caused by circulating IgG that targets two desmosomal proteins, desmoglein 1 and 3, which are crucial for cell–cell adhesion of keratinocytes. Binding of auto-antibodies to desmogleins impairs keratinocyte adhesion, leading to severe blistering disease. Mouse models that recapitulate the human disease have been instrumental in elucidating the detailed pathophysiology. Taking advantage of the fact that desmogleins are specifically targeted in pemphigus, studying humoral and cellular autoimmunity against these autoantigens provides us with an opportunity to understand not only the effector mechanisms of B and T cells in mediating pathology but also how autoreactive lymphocytes are regulated during development in the thymus and post-development in the periphery. This review introduces pemphigus and its subtypes as prototypic autoimmune diseases from which recent basic and translational developments should provide insight into how autoimmunity develops.

Abstract Graft-versus-host disease (GVHD) is the most important determinant for long-term morbidity and mortality in allogeneic stem cell transplantation, affecting approximately 50% of patients. Acute (a)GVHD is a distinctive syndrome of dermatitis, hepatitis and enteritis, while the term chronic (c)GVHD describes a more pleiotropic syndrome. Many clinical manifestations of cGVHD are very similar to those of autoimmune diseases such as lupus erythematosus and scleroderma. In addition, in cGVHD autoantibody formation is a common feature. To investigate the pathogenesis of cGVHD and to study the effect of new treatment modalities, clinically relevant models are of great importance. Recently, we were able to develop a model for GVHD by intravenous transfer of huPBMC in RAG2−/− γc−/− mice (van Rijn et al., Blood102: 2522, 2003). In this study we report on the whole spectrum of histological and immunohistochemical findings in the skin, bowel, tongue, liver, kidney, spleen, bone marrow and lung of 3 mice with acute and 7 with chronic X-GVHD and compare them with those seen in patients with GVHD. All mice showed a ruffled fur and 3 acute and 2 chronic mice had an erythematous skin with loss of hair. Lymphocytic infiltrates and tissue damage were observed in all organs. These lymphocytic infiltrates consisted of T lymphocytes with a surprising predominance of CD4+ cells (75–85%) that was not reflected in the peripheral blood. The kidneys contained variable numbers of lymphocytes, mainly localized in the interstitium. The lungs contained a mild to severe lymphoplasmacellular infiltrate. In three mice there was damage of the bronchial epithelium. 5/7 of the chronic mice showed peribronchial fibrosis. All mice showed a mild to moderate fibrosis in the bone marrow. The bowels contained a very mild lymphocytic infiltrate, but there were no signs of epithelial damage or diarrhoea. Chronic mice demonstrated less lymphocytic infiltrate, more plasma cells and more fibrosis than acute mice. Fibrosis was found in the skin, liver, lungs, spleen and bone marrow. One mouse had severe fibrosis of the liver, spleen, skin and lungs. In later experiments, five more mice sacrificed with chronic GVHD showed a similar histology. Importantly, the livers of the chronic mice showed an auto-immune hepatitis with large amounts of plasma cells. In 5/7 chronic mice even a deposition of human IgA and/or IgG was observed in liver and/or skin. A honeycomb-like pattern was present in the IgA staining, with an IgA-positive surface of the periportal hepatocytes in the liver of 5/7 chronic mice. Ig deposits were also observed in the skin of 4/7 mice. The presence of Ig- and complement-deposits were confirmed in the skin of 3/30 patients cGVHD patients without and 3/3 with blistering diseases. These data provide evidence for a participating role of B cells in the pathogenesis of cGVHD. The beneficial effect of anti-CD20 Ab in cGVHD reported in small scale clinical studies is also consistent with a critical role of B cells in cGVHD-pathology. In summary, the histopathological findings in chronic mice are very similar to the findings in cGVHD. As a consequence, the huPBMC/RAG2−/− γc−/− mouse model provides the unique opportunity to study the contribution of B cells to the pathogenesis of cGVHD.