Molecular mimicry among human proteinase 3 and bacterial antigens: implications for development of c-ANCA associated vasculitis.

Wegener's granulomatosis is an autoimmune disease where autoantibodies target human autoantigen PR3, a serine protease locates on the neutrophil membrane. This disease affects blood small vessels and could be deadly. The origin of these autoantibodies is unknown, but infections have been implicated with autoimmune disease. In this study, we explored potential molecular mimicry between human PR3 and homologous pathogens through analysis. Thirteen serine proteases from human pathogens (, , sp., , , , , , , , and ) shared structural homology and amino acid sequence identity with human PR3. Epitope prediction found an only conserved epitope IVGG, located between residues 59-74. However, multiple alignments showed conserved regions that could be involved in cross-reactivity between human and pathogens serine proteases (90-98, 101-108, 162-169, 267 and 262 residues positions). In conclusion, this is the first report providing evidence about the existence of molecular mimicry between human and pathogens serine proteases, that could explain the origins of autoantibodies found in patients suffering from Wegener's granulomatosis.