Do RA associated HLA-DR molecules bind citrullinated peptides or peptides from PAD4 to help the development of RA specific antibodies to citrullinated proteins?
| Autor: | Nathalie Balandraud, Isabelle Auger, Jean Roudier |
|---|---|
| Přispěvatelé: | Arthrites autoimmunes (AA), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), AUGER, ISABELLE |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
[SDV]Life Sciences [q-bio] Peptide Fibrinogen Autoantigens Arthritis Rheumatoid Epitopes 0302 clinical medicine Protein-Arginine Deiminase Type 4 immune system diseases Genotype Immunology and Allergy skin and connective tissue diseases ComputingMilieux_MISCELLANEOUS chemistry.chemical_classification [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system biology Chemistry Citrullinated peptide binding Anti–citrullinated protein antibody Amino acid [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system Rheumatoid arthritis medicine.drug Protein Binding musculoskeletal diseases Immunology Binding Competitive Peptides Cyclic 03 medical and health sciences HLA-DR medicine Humans Genetic Predisposition to Disease Amino Acid Sequence Gene Alleles Autoantibodies 030203 arthritis & rheumatology HLA-DR association Prevention medicine.disease Molecular biology PAD4 peptide binding 030104 developmental biology biology.protein Anticitrullinated protein antibodies Citrullination Peptides HLA-DRB1 Chains |
| Zdroj: | Journal of Autoimmunity Journal of Autoimmunity, Elsevier, 2021, 116, pp.102542. ⟨10.1016/j.jaut.2020.102542⟩ Journal of Autoimmunity, Elsevier, 2020, pp.102542. ⟨10.1016/j.jaut.2020.102542⟩ |
| ISSN: | 0896-8411 1095-9157 |
| DOI: | 10.1016/j.jaut.2020.102542⟩ |
| Popis: | Purpose Rheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding a five amino acid basic motive, the shared epitope SE). Each HLA-DRB1 genotype defines a genotype specific risk of developing RA. RA is preceded by the emergence of anti citrullinated protein antibodies (ACPAs). Citrullin is a neutral version of arginin, a basic amino acid, formed after post translational modification by Peptidyl Arginyl Deiminases (PADs). HLA-DRB1 genes associated with RA are also associated with ACPAs. Two models might explain this association: - RA associated HLA-DR molecules might bind citrullinated peptides better than non RA associated HLA-DR molecules. - RA associated HLA-DR molecules might bind PAD4 peptide(s) better than non RA associated HLA-DR molecules. Here we tested both models for prediction of HLA-DRB1 genotypic risks of developing RA. Methods We calculated the likelihoods for the 2 HLA-DR molecules encoded by 12 common HLA-DRB1 genotypes to bind at least one randomly chosen peptide from PAD4 or fibrinogen(native or citrullinatd) and compared them with the 12 respective HLA-DRB1genotypic risks of developing RA. Results HLA-DRB1 Genotypic risks of developing RA correlate with likelihoods of binding PAD4 peptides, not citrullinated Fibrinogen peptides. Thus, the molecular basis for the association of HLA-DR and ACPA positive RA is most likely the capability for RA associated HLA-DR molecules to bind peptides(s) from PAD4. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect