Israel Medical Association Journal

Basement membranes form an anatomic barrier that contains connective tissue. They are composed of type IV collagen, laminin and proteoglycans. Anti-basement membrane antibodies bind to the non-collagen site of the α3 chain of type IV collagen. A group of renal diseases, pulmonary diseases and perhaps others affecting different organs have long been associated with the presence of antibodies directed against glomerular basement membrane (GBM), alveolar basement membrane and tubular basement membrane. Goodpasture disease has a frequency of 0.5 to 1 case by million/year, and is responsible for up to 20% of crescentic glomerulonephritis in renal biopsy. It has been associated with genetic and immune abnormalities and there are usually environmental triggers preceding clinical onset. Renal disease can occur isolated or in association with pulmonary hemorrhage. In general, renal disease has a rapid progression that determines severe compromise, with rare spontaneous resolution. The diagnosis of Goodpasture disease requires the presence of the anti-GBM antibody, either in circulation or in renal tissue. The prognosis of non-treated patients is poor. The standard of care is plasma exchange combined with prednisone and cyclophosphamide. Anti-GBM antibody levels must be monitored frequently until their disappearance, and then every 6 months to confirm sustained remission in the absence of clinical signs of recurrence. Prognosis of the disease is strongly associated with its initial presentation. Survival rates are related to the degree of renal compromise at onset of the disease. Recurrence of the disease post-transplantation is low.

Autoinflammatory (AIF) and autoimmune (AIM) diseases are chronic immune disorders characterized by dysregulation of the immune system. Most AIF diseases are monogenic diseases which lead to hyperactivation of the inflammasome and release of pro-inflammatory cytokines, such as interleukin-1 (IL-1) and IL-18, resulting in tissue inflammation. Besides, the main feature of autoimmune diseases is the loss of tolerance of the adaptive immune cells against self antigens. Most AIF diseases are polygenic and numerous immune pathogens are involved in organ damage. The involvement of some AIF-associated mechanisms in AIM diseases, i.e., the activation of the inflammasome and the role of IL-1, was recently recognized. Moreover, some single nucleotide polymorphisms of the inflammasome genes have been proven to be involved in the development of AIF-related inflammatory features in autoimmune patients. These observations raise the possibility of using some anti-inflammatory drugs, like IL-1 antagonists, in autoimmune diseases with autoinflammatory features.