PAD2 immunization induces ACPA in wild‐type and HLA‐DR4 humanized mice. Issue 9 (25th June 2022)

• Record Type: Journal Article
• Authors: Hemon, Marie F.; Lambert, Nathalie C.; Roudier, Jean; Auger, Isabelle
• Is Part Of: European journal of immunology. Volume 52:Issue 9(2022)
• Page Start: 1464
• Page End: 1473
• Publication Date: 2022-06-25
• Subjects: ACPAs -- HLA‐DR4 -- Humanized mice -- PADs -- Rheumatoid arthritis; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202249889
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: Rheumatoid arthritis (RA) is associated with HLA‐DRB1 alleles expressing the "shared epitope." RA is usually preceded by the emergence of anti‐citrullinated protein autoantibodies (ACPAs). ACPAs recognize citrulline residues on numerous proteins. Conversion of arginine into citrulline is performed by enzymes called peptidyl arginine deiminases (PADs). We have previously demonstrated that C3H mice immunized with PADs can produce ACPAs by a hapten‐carrier mechanism. Here, we address the influence of HLA‐DR alleles in this model in mice expressing RA‐associated HLA‐DRB1*04:01 (KO/KI*04:01), HLA‐DRB1*04:04 (KO/KI*04:04), or non‐RA‐associated HLA‐DRB1*04:02 (KO/KI*04:02) after murine PAD2 immunization. Immunization with mPAD2 triggers production of ACPAs in wild‐type (WT) and HLA‐DR4 C57BL/6 mice. Both I‐A b and HLA‐DR are involved in the activation of mPAD2‐specific T lymphocytes. Among HLA‐DR4 mice, mice expressing RA‐associated HLA‐DRB1*04:01 are the best responders to mPAD2 and the best anti‐citrullinated peptide antibody producers. Abstract : After PAD2 immunization, B cells specific for citrullinated peptides internalize PAD2/citrullinated peptide complexes and present PAD2 peptides to T cells helping ACPA production as observed in wild‐type and HLA‐DR4 humanized mice.