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 neutrophils membrane. This disease affects blood small vessels and could be deadly. Origin of these autoantibodies is unknow, but infections have been implicated with autoimmune disease. In this study, we explored potential molecular mimicry between human PR3 and homologous in pathogens trough in silico analysis. Thirteen serine proteases from human pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Salmonella sp, Streptococcus suis, Vibrio parahaemolyticus, Bacteroides fragilis, Enterobacter ludwigii, Vibrio alginolyticus, Staphylococcus haemolyticus, Enterobacter cloacae, Escherichia coli, and Pseudomonas aeruginosa) shared structural homology and aminoacid sequence identity with human PR3. Epitope prediction found an only conserved epitope IVGG, located between residues 59 -74. However, multiple alignment 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 a first report providing in silico evidence about existence of molecular mimicry between human and pathogens serine proteases, that could explain origins of autoantibodies found in patients suffering Wegener’s granulomatosis.