Cross reactivity of antibodies against microbial proteins to human tissues as basis of Crohns disease and other autoimmune diseases
Peilin Zhang, Lawrence M. Minardi, J. Todd Kuenstner, Stephen M. Zekan, Feng Zhu, Yinling Hu, Rusty Kruzelock
Abstract
BackgroundAutoimmune disease is generally a systemic inflammatory response with production of autoantibodies. In this study, we investigated the anti-microbial antibodies in circulation in cases of Crohns disease (CD), Sjogrens syndrome (SS) and other autoimmune disease and their roles in the pathogenesis of these autoimmune diseases.\n\nMaterial and methodsWestern blot was used to determine the reactivity of human plasmas from patients with CD and SS as the primary antibodies against the whole microbial extracts. The microbial proteins reactive to patients plasma were further identified and the modified sandwich ELISA assays were used to determine the blood levels of antibodies against these microbial proteins in patients with CD and SS. Antibodies against the microbial proteins are used for immunohistochemical staining of normal human tissue.\n\nResultsA group of 7 microbial proteins was identified reactive to the plasmas of patients with CD and SS including DNA-directed RNA polymerase B (RPOB), and elongation factor G (EF-G) from Staphylococcus aureus and Staphylococcus pseudintermedius (S. aureus and S. pseudintermedius), ATP synthase alpha (ATP5a) and heat shock protein 65 (Hsp65) from Mycobacterium avium subspecies paratuberculosis (MAP), elongation factor Tu (EF-Tu) and outer membrane porin C (ompC) from Escherichia Coli (E. coli). Anti-microbial antibodies can cross-react to normal human tissues. The levels of antibodies against the microbial proteins are significantly elevated in the patients with CD and SS.\n\nConclusionThe levels of antibodies against the microbial proteins are significantly elevated in CD and SS. The cross-reactivity of the anti-microbial antibodies to human tissue provides a new mechanism of pathogenesis of autoimmune diseases such as CD and SS.
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