Anti-Carbamylated Fibrinogen Antibodies Might Be Associated With a Specific Rheumatoid Phenotype and Include a Subset Recognizing In Vivo Epitopes of Its γ Chain One of Which Is Not Cross Reactive With Anti-Citrullinated Protein Antibodies
To identify the targets recognized by anti-carbamylated protein antibodies (anti-CarP) in patients with early Rheumatoid Arthritis (RA), to study the cross-reactivity between anti-CarP and anti-citrullinated protein antibodies (ACPA) and to evaluate their prognostic value. 331 patients (184 RA and 1...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.733511/full |
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| author | Pauline Brevet Pauline Brevet Claire Lattard Claire Lattard Clément Guillou Pascal Rottenberg Patrice Fardellone Xavier Le-Loët Thierry Lequerré Thierry Lequerré Pascal Cosette Olivier Boyer Olivier Boyer Manuel Fréret Manuel Fréret Olivier Vittecoq Olivier Vittecoq |
| author_facet | Pauline Brevet Pauline Brevet Claire Lattard Claire Lattard Clément Guillou Pascal Rottenberg Patrice Fardellone Xavier Le-Loët Thierry Lequerré Thierry Lequerré Pascal Cosette Olivier Boyer Olivier Boyer Manuel Fréret Manuel Fréret Olivier Vittecoq Olivier Vittecoq |
| author_sort | Pauline Brevet |
| collection | DOAJ |
| description | To identify the targets recognized by anti-carbamylated protein antibodies (anti-CarP) in patients with early Rheumatoid Arthritis (RA), to study the cross-reactivity between anti-CarP and anti-citrullinated protein antibodies (ACPA) and to evaluate their prognostic value. 331 patients (184 RA and 147 other rheumatisms) from the Very Early Arthritis (VErA) French cohort were analyzed. We performed mass spectrometry analysis of RA sera displaying anti-CarP activity and epitope mapping of the carbamylated fibrinogen γ chain to identify immunodominant peptides. The specificity of these targets was studied using competition assays with the major antigens recognized by ACPA. The prognostic value of anti-carbamylated fibrinogen IgG antibodies (ACa-Fib IgG) was compared to that of anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-CarP using an in-house ELISA. Besides the α chain, the γ chain of fibrinogen, particularly one immunodominant epitope that has a specific reactivity, was identified as a circulating carbamylated target in sera. The prevalence of ACa-Fib was 37% at baseline and 10.9% for anti-CCP-negative RA. In anti-CCP-negative patients, ACa-Fib positivity was associated with a more inflammatory and erosive disease at baseline but not with rapid radiological progression, which remains strongly related to anti-CCP antibodies. Fibrinogen seems to be one of the antigens recognized in vivo by the anti-CarP response, particularly 2 epitopes of the γ chain, one of which is not cross reactive with ACPA. This specificity might be associated with a distinct clinical phenotype since ACa-Fib IgG were shown to be linked to systemic inflammation in very early RA but not to rapid radiological progression. |
| first_indexed | 2024-12-14T00:22:00Z |
| format | Article |
| id | doaj.art-5c9d1f55529b4c27b88f502d1ad60f99 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T00:22:00Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5c9d1f55529b4c27b88f502d1ad60f992022-12-21T23:25:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.733511733511Anti-Carbamylated Fibrinogen Antibodies Might Be Associated With a Specific Rheumatoid Phenotype and Include a Subset Recognizing In Vivo Epitopes of Its γ Chain One of Which Is Not Cross Reactive With Anti-Citrullinated Protein AntibodiesPauline Brevet0Pauline Brevet1Claire Lattard2Claire Lattard3Clément Guillou4Pascal Rottenberg5Patrice Fardellone6Xavier Le-Loët7Thierry Lequerré8Thierry Lequerré9Pascal Cosette10Olivier Boyer11Olivier Boyer12Manuel Fréret13Manuel Fréret14Olivier Vittecoq15Olivier Vittecoq16Rouen University Hospital, Department of Rheumatology & CIC-CRB1404, Rouen, FranceNormandie University, UNIROUEN, INSERM, U1234, Rouen, FranceRouen University Hospital, Department of Rheumatology & CIC-CRB1404, Rouen, FranceRouen University Hospital, Department of Pharmacology, Rouen, FranceNormandie University, UNIROUEN, PISSARO Proteomics Facility & PBS-UMR6270 CNRS, IRIB, Rouen, FranceRouen University Hospital, Department of Rheumatology & CIC-CRB1404, Rouen, FranceAmiens University Hospital, Department of Rheumatology, Amiens, FranceRouen University Hospital, Department of Rheumatology & CIC-CRB1404, Rouen, FranceRouen University Hospital, Department of Rheumatology & CIC-CRB1404, Rouen, FranceNormandie University, UNIROUEN, INSERM, U1234, Rouen, FranceNormandie University, UNIROUEN, PISSARO Proteomics Facility & PBS-UMR6270 CNRS, IRIB, Rouen, FranceNormandie University, UNIROUEN, INSERM, U1234, Rouen, FranceRouen University Hospital, Department of Immunology, Rouen, FranceRouen University Hospital, Department of Rheumatology & CIC-CRB1404, Rouen, FranceNormandie University, UNIROUEN, INSERM, U1234, Rouen, FranceRouen University Hospital, Department of Rheumatology & CIC-CRB1404, Rouen, FranceNormandie University, UNIROUEN, INSERM, U1234, Rouen, FranceTo identify the targets recognized by anti-carbamylated protein antibodies (anti-CarP) in patients with early Rheumatoid Arthritis (RA), to study the cross-reactivity between anti-CarP and anti-citrullinated protein antibodies (ACPA) and to evaluate their prognostic value. 331 patients (184 RA and 147 other rheumatisms) from the Very Early Arthritis (VErA) French cohort were analyzed. We performed mass spectrometry analysis of RA sera displaying anti-CarP activity and epitope mapping of the carbamylated fibrinogen γ chain to identify immunodominant peptides. The specificity of these targets was studied using competition assays with the major antigens recognized by ACPA. The prognostic value of anti-carbamylated fibrinogen IgG antibodies (ACa-Fib IgG) was compared to that of anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-CarP using an in-house ELISA. Besides the α chain, the γ chain of fibrinogen, particularly one immunodominant epitope that has a specific reactivity, was identified as a circulating carbamylated target in sera. The prevalence of ACa-Fib was 37% at baseline and 10.9% for anti-CCP-negative RA. In anti-CCP-negative patients, ACa-Fib positivity was associated with a more inflammatory and erosive disease at baseline but not with rapid radiological progression, which remains strongly related to anti-CCP antibodies. Fibrinogen seems to be one of the antigens recognized in vivo by the anti-CarP response, particularly 2 epitopes of the γ chain, one of which is not cross reactive with ACPA. This specificity might be associated with a distinct clinical phenotype since ACa-Fib IgG were shown to be linked to systemic inflammation in very early RA but not to rapid radiological progression.https://www.frontiersin.org/articles/10.3389/fimmu.2021.733511/fullvery early rheumatoid arthritisanti-carbamylated protein antibodies (anti-CarP)fibrinogenACPAprognosis |
| spellingShingle | Pauline Brevet Pauline Brevet Claire Lattard Claire Lattard Clément Guillou Pascal Rottenberg Patrice Fardellone Xavier Le-Loët Thierry Lequerré Thierry Lequerré Pascal Cosette Olivier Boyer Olivier Boyer Manuel Fréret Manuel Fréret Olivier Vittecoq Olivier Vittecoq Anti-Carbamylated Fibrinogen Antibodies Might Be Associated With a Specific Rheumatoid Phenotype and Include a Subset Recognizing In Vivo Epitopes of Its γ Chain One of Which Is Not Cross Reactive With Anti-Citrullinated Protein Antibodies Frontiers in Immunology very early rheumatoid arthritis anti-carbamylated protein antibodies (anti-CarP) fibrinogen ACPA prognosis |
| title | Anti-Carbamylated Fibrinogen Antibodies Might Be Associated With a Specific Rheumatoid Phenotype and Include a Subset Recognizing In Vivo Epitopes of Its γ Chain One of Which Is Not Cross Reactive With Anti-Citrullinated Protein Antibodies |
| title_full | Anti-Carbamylated Fibrinogen Antibodies Might Be Associated With a Specific Rheumatoid Phenotype and Include a Subset Recognizing In Vivo Epitopes of Its γ Chain One of Which Is Not Cross Reactive With Anti-Citrullinated Protein Antibodies |
| title_fullStr | Anti-Carbamylated Fibrinogen Antibodies Might Be Associated With a Specific Rheumatoid Phenotype and Include a Subset Recognizing In Vivo Epitopes of Its γ Chain One of Which Is Not Cross Reactive With Anti-Citrullinated Protein Antibodies |
| title_full_unstemmed | Anti-Carbamylated Fibrinogen Antibodies Might Be Associated With a Specific Rheumatoid Phenotype and Include a Subset Recognizing In Vivo Epitopes of Its γ Chain One of Which Is Not Cross Reactive With Anti-Citrullinated Protein Antibodies |
| title_short | Anti-Carbamylated Fibrinogen Antibodies Might Be Associated With a Specific Rheumatoid Phenotype and Include a Subset Recognizing In Vivo Epitopes of Its γ Chain One of Which Is Not Cross Reactive With Anti-Citrullinated Protein Antibodies |
| title_sort | anti carbamylated fibrinogen antibodies might be associated with a specific rheumatoid phenotype and include a subset recognizing in vivo epitopes of its γ chain one of which is not cross reactive with anti citrullinated protein antibodies |
| topic | very early rheumatoid arthritis anti-carbamylated protein antibodies (anti-CarP) fibrinogen ACPA prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.733511/full |
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