Title: Sequence-based prediction of linear autoepitopes involved in pathogenesis of IPAH and the corresponding organism sources of molecular mimicry

Authors: Jaroslav Kubrycht; Jana Novotná

Addresses: Department of Physiology, Center for Cardiovascular Research, Charles University, Prague, Czech Republic ' Department of Medical Chemistry and Clinical Biochemistry, Charles University, Prague, Czech Republic

Abstract: We proposed here a sequence-based approach predicting some microorganisms as possible sources of autoantigen-related molecular mimicry concerning Idiopathic Pulmonary Arterial Hypertension (IPAH) and related hypertension mostly accompanying autoimmune diseases and AIDS (APAH). This approach (SPECIES_VALENCE) processes the database occurrences of linear autoepitope-related short Dense Quasi-Pattern Sequences (DQPA) generated based on identities of important autoantigenic sequences. The corresponding enumeration comprises two types of statistical evaluations performed in each of eight proposed models. Based on this enumeration, we selected nine microorganisms, whereas revaluation of the obtained scoring values restricted Pseudomonas aeruginosa, Aspergillus fumigatus and the two co-infecting herpes viruses (Epstein Barr virus and cytomegalovirus) as most favourable. The results are discussed in terms of (a) the validity of increased DQPA occurrence in functionally correlated sequences, (b) the possible mechanisms leading to autoantibody response, (c) selected additional pathogenic effects of predicted microorganisms and (d) possible effects of cross-reactivities and immune tolerance.

Keywords: APAH; autoantigens; fibrillin; autoimmune diseases; AIDS; IPAH pathogenesis; metalloproteinase; molecular mimicry; proline; remodelling; sequence based prediction; linear autoepitopes; organism sources; idiopathic pulmonary arterial hypertension; dense quasi-pattern sequences; DQPA; autoantibody response; pathogenic effects; microorganisms; cross-reactivities; immune tolerance; bioinformatics.

DOI: 10.1504/IJBRA.2014.065244

International Journal of Bioinformatics Research and Applications, 2014 Vol.10 No.6, pp.587 - 612

Available online: 20 Oct 2014 *

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