In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope
ObjectivesRheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding the shared epitope (SE), a 5-amino acid motive. RA is usually preceded by the emergence of anti-citrullinated protein/peptide antibodies (ACPAs). Citrulline is a neutral amino acid resulting from post-translational modifi...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.692041/full |
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| author | Guillaume Larid Mikael Pancarte Géraldine Offer Cyril Clavel Marielle Martin Vincent Pradel Isabelle Auger Pierre Lafforgue Jean Roudier Jean Roudier Guy Serre Nathalie Balandraud Nathalie Balandraud |
| author_facet | Guillaume Larid Mikael Pancarte Géraldine Offer Cyril Clavel Marielle Martin Vincent Pradel Isabelle Auger Pierre Lafforgue Jean Roudier Jean Roudier Guy Serre Nathalie Balandraud Nathalie Balandraud |
| author_sort | Guillaume Larid |
| collection | DOAJ |
| description | ObjectivesRheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding the shared epitope (SE), a 5-amino acid motive. RA is usually preceded by the emergence of anti-citrullinated protein/peptide antibodies (ACPAs). Citrulline is a neutral amino acid resulting from post-translational modification of arginine involved in peptidic bounds (arginyl residue) by PeptidylArginine Deiminases (PADs). ACPAs recognize epitopes from citrullinated human fibrin(ogen) (hFib) and can be specifically detected by the AhFibA assay. Five citrullinated peptides derived from hFib together represent almost all of the epitopes recognized by patients with ACPA-positive RA, namely: α36–50cit, α171–185cit, α501–515cit, α621–635cit, and β60–74cit. The use of antibody fine specificities as markers of clinical phenotypes has become a major challenge. Our objective was to study whether RA clinical characteristics and HLA-DRB1 genetic background were associated with a specific reactivity against the epitopes borne by the five peptides.Methods184 ACPA-positive RA patients fulfilling the 2010 ACR/EULAR criteria were studied. Patient characteristics including HLA-DRB1 genotype, were collected from their medical files. Anti-CCP2 antibodies, AhFibA, and antibodies against the five citrullinated hFib (hFib-cit) peptides were analyzed by ELISA.ResultsAnti-α505-515cit antibodies were associated with HLA-DRB1*04:01 (OR = 5.52 [2.00 – 13.64]; p = 0.0003). High level anti-α505-515cit antibodies were associated with rheumatoid nodules (OR = 2.71 [1.00 – 7.16], p= 0.044).ConclusionImmune complexes containing anti-α501-515cit antibodies and rheumatoid factors might be involved in the development of rheumatoid nodules on the HLA-DRB1*04:01 background. Apheresis of these epitope-specific antibodies might be a new therapeutic opportunity for patients with rheumatoid nodules. |
| first_indexed | 2024-12-14T09:24:44Z |
| format | Article |
| id | doaj.art-ea73d478859a42a687b2d323215c52a9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T09:24:44Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-ea73d478859a42a687b2d323215c52a92022-12-21T23:08:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-06-011210.3389/fimmu.2021.692041692041In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin EpitopeGuillaume Larid0Mikael Pancarte1Géraldine Offer2Cyril Clavel3Marielle Martin4Vincent Pradel5Isabelle Auger6Pierre Lafforgue7Jean Roudier8Jean Roudier9Guy Serre10Nathalie Balandraud11Nathalie Balandraud12Rhumatologie, Institut du Mouvement et de l'appareil Locomoteur (IML), Assistance Publique - Hôpitaux de Marseille (AP-HM), Marseille, FranceUniversité de Toulouse, INSERM, UMRs 1056, UDEAR, Hôpital Purpan, Toulouse, FranceUniversité de Toulouse, INSERM, UMRs 1056, UDEAR, Hôpital Purpan, Toulouse, FranceUniversité de Toulouse, INSERM, UMRs 1056, UDEAR, Hôpital Purpan, Toulouse, FranceAix Marseille Université, INSERM UMRs 1097, Arthrites autoimmunes, Marseille, FranceCEIP de Marseille (PACA-Corse, Centre Associé), Laboratoire de Santé Publique, Faculté de Médecine, Marseille, FranceAix Marseille Université, INSERM UMRs 1097, Arthrites autoimmunes, Marseille, FranceRhumatologie, Institut du Mouvement et de l'appareil Locomoteur (IML), Assistance Publique - Hôpitaux de Marseille (AP-HM), Marseille, FranceRhumatologie, Institut du Mouvement et de l'appareil Locomoteur (IML), Assistance Publique - Hôpitaux de Marseille (AP-HM), Marseille, FranceAix Marseille Université, INSERM UMRs 1097, Arthrites autoimmunes, Marseille, FranceUniversité de Toulouse, INSERM, UMRs 1056, UDEAR, Hôpital Purpan, Toulouse, FranceRhumatologie, Institut du Mouvement et de l'appareil Locomoteur (IML), Assistance Publique - Hôpitaux de Marseille (AP-HM), Marseille, FranceAix Marseille Université, INSERM UMRs 1097, Arthrites autoimmunes, Marseille, FranceObjectivesRheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding the shared epitope (SE), a 5-amino acid motive. RA is usually preceded by the emergence of anti-citrullinated protein/peptide antibodies (ACPAs). Citrulline is a neutral amino acid resulting from post-translational modification of arginine involved in peptidic bounds (arginyl residue) by PeptidylArginine Deiminases (PADs). ACPAs recognize epitopes from citrullinated human fibrin(ogen) (hFib) and can be specifically detected by the AhFibA assay. Five citrullinated peptides derived from hFib together represent almost all of the epitopes recognized by patients with ACPA-positive RA, namely: α36–50cit, α171–185cit, α501–515cit, α621–635cit, and β60–74cit. The use of antibody fine specificities as markers of clinical phenotypes has become a major challenge. Our objective was to study whether RA clinical characteristics and HLA-DRB1 genetic background were associated with a specific reactivity against the epitopes borne by the five peptides.Methods184 ACPA-positive RA patients fulfilling the 2010 ACR/EULAR criteria were studied. Patient characteristics including HLA-DRB1 genotype, were collected from their medical files. Anti-CCP2 antibodies, AhFibA, and antibodies against the five citrullinated hFib (hFib-cit) peptides were analyzed by ELISA.ResultsAnti-α505-515cit antibodies were associated with HLA-DRB1*04:01 (OR = 5.52 [2.00 – 13.64]; p = 0.0003). High level anti-α505-515cit antibodies were associated with rheumatoid nodules (OR = 2.71 [1.00 – 7.16], p= 0.044).ConclusionImmune complexes containing anti-α501-515cit antibodies and rheumatoid factors might be involved in the development of rheumatoid nodules on the HLA-DRB1*04:01 background. Apheresis of these epitope-specific antibodies might be a new therapeutic opportunity for patients with rheumatoid nodules.https://www.frontiersin.org/articles/10.3389/fimmu.2021.692041/fullACPArheumatoid arthritisHLA-DRB1AhFibAcitrullinated peptides 2 |
| spellingShingle | Guillaume Larid Mikael Pancarte Géraldine Offer Cyril Clavel Marielle Martin Vincent Pradel Isabelle Auger Pierre Lafforgue Jean Roudier Jean Roudier Guy Serre Nathalie Balandraud Nathalie Balandraud In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope Frontiers in Immunology ACPA rheumatoid arthritis HLA-DRB1 AhFibA citrullinated peptides 2 |
| title | In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope |
| title_full | In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope |
| title_fullStr | In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope |
| title_full_unstemmed | In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope |
| title_short | In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope |
| title_sort | in rheumatoid arthritis patients hla drb1 04 01 and rheumatoid nodules are associated with acpa to a particular fibrin epitope |
| topic | ACPA rheumatoid arthritis HLA-DRB1 AhFibA citrullinated peptides 2 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.692041/full |
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