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Immunomic analysis of syovial fluid exosomes of rheumatic diseases patients

In addition to soluble proteins and mediators, cells also release membrane vesicles in the extracellular environment, exosomes and apototic blebs. Apoptotic blebs have been studied and contain multiple autoantigens. Exosomal protein content and its functions are starting to be unraveled. During an immune response the 40 nm particles are formed, on the surface they have Class I and II antigens as well as viral proteins or other proteins like heatshock proteins Hsp 70 and 90, or B7 a costimmulatory molecule. Recent studies showed that exosomes can stimulate T cells directly or bind to dendritic cells, suggesting a general function for exosomes in immune response. The mechanism of action in vivo is poorly understood. Exosomes seem to stimulate T cells and have been shown to induce tumor rejection when loaded with tumor peptide. The composition of synovial exosomes has so far not been studied or compared to other diseases and normals. Autoimmune diseases like rheumatoid arthitis (RA) are characterized by autoantibodies to different proteins like BiP, hnRNPs and p205 which has not been charaterized in its nature. Different synovial exosomes from RA patients, reactive arthritis, and osteoarthritis patients and controls have been purified and analysed for specific autoantigenic content by immunoblotting. P205 was found in all exosomal preperations in contrast to Bip and hnRNP A2, which could not be detected in the synovial exosomes fractions so far. Synovial Exosomal proteins haved been analysed by immunoblotting after 2D electrophoresis and immuneprecipitation. Based on that methods the specific autoantigenic protein content can be analysed now. After revealing the primary structure and molecular identity of the autoantigens, recombinant autoantigens will be produced and used for diagnostic as well as immunemodulatory purposes. In summary, the autoantigenic analysis of synovial exosomes revealed that p205 is associated with exosomal particles. The investigation of the synovial exosome protein content as well as the analysis of B and T-cell sitmulation potential, may thereby possibly lead to novel diagnostic and therapeutic strategies in rheumatic diseases.

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Sternjak, A., Bläβ, S., Metzkow, S. et al. Immunomic analysis of syovial fluid exosomes of rheumatic diseases patients. Arthritis Res Ther 4 (Suppl 1), 75 (2002).

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