Abstract
Background: In autoimmune vasculitis, autoantibodies to Human Proteinase 3 (PR3), a human serine protease, seems to have a role on the inception of c-ANCA associated vasculitis. The origin of this autoreactive response remains unclear. However, for several autoreactive responses, molecular mimicry between environmental antigens and human proteins is key to trigger autoantibodies and finally autoimmunity manifestations. Considering that PR3 is a serine protease and house dust mite (HDM) group 3 allergens share this biochemical activity, the aim of this study was to identify cross-reactive epitopes between serine proteases from human and mites using an in silico approach. Methods: Multi alignment among amino acid sequences of PR3 and HDM group 3 allergens was performed to explore identity and structural homology. ElliProandBepiPred in silicotoolswereusedtopredictBand T cell epitopes. Consurf tool was used to conduct identification of conserved regions in serine proteases family. Results: PR3 and HDM group 3 allergens shared moderate identity and structural homology (rootmeansquaredeviation<1). One B cell cross reactive epitope among serine proteases was identified (29I, 30V, 31G, 32G, 34E, 36K, 37A, 38L, 39A and 54C) and two T cell epitopes. Conclusions: PR3 have structural homology and share cross reactive epitopes with HDM group 3 allergens.
Highlights
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a life-threatening autoimmune disease affecting small vessels, compromising the respiratory mucosa, skin, lung, and the kidney[1]
While proinflammatory effector T cells have been implicated in vasculitis pathogenesis[2], a specific Proteinase 3 (PR3) T cell epitope has not been reported in AAV patients[3]
The Der p 3 tertiary structure exhibited a typical fold of serine protease family, conformed by four α-helixes and fifteen β-strands with structural homology with PR3 (RMSD = 0.8) (Figure 2)
Summary
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a life-threatening autoimmune disease affecting small vessels, compromising the respiratory mucosa, skin, lung, and the kidney[1]. Due to its enzymatic activity, it degrades various intercellular gap-junction proteins and collagen and may play a role in neutrophil transendothelial migration This protein is an important autoantigen in AAV, and sera from patients with severe and relapsing forms of the disease can bind it in IgG ELISA assays[4,5,6]. Autoantibodies to Human Proteinase 3 (PR3), a human serine protease, seems to have a role on the inception of c-ANCA associated vasculitis The origin of this autoreactive response remains unclear. One B cell cross reactive epitope among serine proteases was identified (29I, 30V, 31G, 32G, 34E, 36K, 37A, 38L, 39A and 54C) and two T cell epitopes
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