Exosome Complex - Disease - Autoimmunity

Autoimmunity

The exosome complex is the target of autoantibodies in patients that suffer from various autoimmune diseases. These autoantibodies are mainly found in people that suffer from the PM/Scl overlap syndrome, an autoimmune disease in which patients have symptoms from both scleroderma and either polymyositis or dermatomyositis. Autoantibodies can be detected in the serum of patients by a variety of assays. In the past, the most commonly used methods were double immunodiffusion using calf thymus extracts, immunofluorescence on HEp-2 cells or immunoprecipitation from human cell extracts. In immunoprecipitation assays with sera from anti-exosome positive sera, a distinctive set of proteins is precipitated. Already years before the exosome complex was identified, this pattern was termed the PM/Scl complex. Immunofluorescence using sera from these patients usually shows a typical staining of the nucleolus of cells, which sparked the suggestion that the antigen recognized by autoantibodies might be important in ribosome synthesis. More recently, recombinant exosome proteins have become available and these have been used to develop line immunoassays (LIAs) and enzyme linked immunosorbent assays (ELISAs) for detecting these antibodies.

In these diseases, antibodies are mainly directed against two of the proteins of the complex, called PM/Scl-100 (the RNase D like protein) and PM/Scl-75 (one of the RNase PH like proteins from the ring) and antibodies recognizing these proteins are found in approximately 30% of patients with the PM/Scl overlap syndrome. Although these two proteins are the main target of the autoantibodies, other exosome subunits and associated proteins (like C1D) can be targeted in these patients. At the current time, the most sensitive way to detect these antibodies is by using a peptide, derived from the PM/Scl-100 protein, as the antigen in an ELISA, instead of complete proteins. By this method, autoantibodies are found in up to 55% of patients with the PM/Scl overlap syndrome, but they can also be detected in patients suffering from either scleroderma, polymyositis, or dermatomyositis alone.

As the autobodies are found mainly in patients that have characteristics of several different autoimmune diseases, the clinical symptoms of these patients can vary widely. The symptoms that are seen most often are the typical symptoms of the individual autoimmune diseases and include Raynaud's phenomenon, arthritis, myositis and scleroderma. Treatment of these patients is symptomatic and is similar to treatment for the individual autoimmune disease, often involving either immunosuppressive or immunomodulating drugs.