title: Sequence-based prediction of linear autoepitopes involved in pathogenesis of IPAH and the corresponding organism sources of molecular mimicry.
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.
authors.affiliation: Department of Physiology, Center for Cardiovascular Research, Charles University, Prague, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kubrycht
authors.affiliation: Department of Medical Chemistry and Clinical Biochemistry, Charles University, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Novotná
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D000939:Epitopes / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D065627:Familial Primary Pulmonary Hypertension / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D018716:Molecular Mimicry / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D020539:Sequence Analysis, Protein / Q000379:methods*; D013045:Species Specificity
chemical_list: D000939:Epitopes
keywords: AIDS; APAH; DQPA; IPAH pathogenesis; autoantibody response; autoantigens; autoimmune diseases; bioinformatics; cross–reactivities; dense quasi–pattern sequences; fibrillin; idiopathic pulmonary arterial hypertension; immune tolerance; linear autoepitopes; metalloproteinase; microorganisms; molecular mimicry; organism sources; pathogenic effects; proline; remodelling; sequence based prediction