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A High Throughput MHC II Binding Assay for Quantitative Analysis of Peptide Epitopes
Published on: March 25, 2014
Sequence-based prediction of linear autoepitopes involved in pathogenesis of IPAH and the corresponding organism
Jaroslav Kubrycht1, Jana Novotná2
1Department of Physiology, Center for Cardiovascular Research, 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.
Insights
This study introduces a sequence-based method to identify microorganisms potentially causing autoimmune responses in Idiopathic Pulmonary Arterial Hypertension (IPAH). Key findings implicate Pseudomonas aeruginosa, Aspergillus fumigatus, Epstein Barr virus, and cytomegalovirus.
Area of Science:
- Immunology
- Microbiology
- Pulmonology
Background:
- Idiopathic Pulmonary Arterial Hypertension (IPAH) and related conditions often involve autoimmune processes.
- Molecular mimicry, where microbial antigens resemble host autoantigens, is a proposed mechanism in autoimmune diseases.
Purpose of the Study:
- To develop and apply a sequence-based computational approach (SPECIES_VALENCE) to predict microorganisms implicated in autoantigen-related molecular mimicry.
- To identify specific microbial species that may trigger autoimmune responses contributing to IPAH and associated conditions.
Main Methods:
- Utilized a novel sequence-based approach (SPECIES_VALENCE) to analyze Dense Quasi-Pattern Sequences (DQPA) associated with autoepitopes.
- Performed statistical evaluations across eight predictive models to score potential microbial sources.
- Filtered and ranked microorganisms based on DQPA occurrence and statistical significance.
Main Results:
- Identified nine candidate microorganisms potentially involved in molecular mimicry.
- Narrowed down the list to Pseudomonas aeruginosa, Aspergillus fumigatus, Epstein Barr virus, and cytomegalovirus as the most probable triggers.
- Results suggest these microbes may initiate or exacerbate autoimmune responses in IPAH.
Conclusions:
- The SPECIES_VALENCE approach effectively predicts microbial involvement in autoimmune diseases like IPAH.
- Pseudomonas aeruginosa, Aspergillus fumigatus, and specific herpesviruses are highlighted as key targets for further investigation.
- Understanding these microbial triggers could lead to novel diagnostic and therapeutic strategies for IPAH.
