David A Bell1, Sallie Elhayek1, Ewa Cairns2, Lillian Barra3. 1. Department of Medicine, Division of Rheumatology, the University of Western Ontario, London, Ontario, Canada. 2. Department of Medicine, Division of Rheumatology, and Department of Microbiology and Immunology, the University of Western Ontario, London, Ontario, Canada. 3. Department of Medicine, Division of Rheumatology, and Department of Microbiology and Immunology, the University of Western Ontario, London, Ontario, Canada. barralillian@hotmail.com.
Abstract
OBJECTIVES: The majority of rheumatoid arthritis (RA) patients express anti-citrullinated protein antibodies (ACPA). Unaffected first-degree relatives of RA patients (FDR) also express ACPA, commonly of the IgA isotype. IgG anti-homocitrullinated/carbamylated protein antibodies (AHCPA) have been detected in both RA and FDR. It is unknown whether other isotypes are expressed. We aim to investigate the AHCPA isotype profile in unaffected FDR of RA patients. METHODS: The enrolled subjects were examined by a rheumatologist. FDR and healthy controls (HC) were excluded if they had swollen joints. Serum AHCPA targeting homocitrullinated fibrinogen was determined using enzyme linked immunoabsorbant assay (ELISA). FDR were genotyped for HLA-DR4 alleles encoding the shared epitope (SE). RESULTS: 125 RA (35 probands), 61 FDR and 40 HC were included. 20% of FDR expressed IgG AHCPA, compared to 30% in RA patients and 5% in HC (p=0.0010 for RA vs. HC). Levels of IgG AHCPA in FDR were similar to RA. FDR rarely expressed IgM (8%) and did not express IgA AHCPA. 20% of RA and 13% of HC subjects expressed IgM, but very few expressed IgA AHCPA (<7% in both groups). AHCPA expression in FDR was not significantly associated with joint symptoms, smoking or SE. CONCLUSIONS: IgG AHCPA is the most commonly expressed isotype in RA and FDR. The significance of IgG AHCPA in FDR is unclear as it was not associated with joint symptoms or other risk factors for RA. Longitudinal studies are needed to determine whether AHCPA is meaningful in populations at risk for RA.
OBJECTIVES: The majority of rheumatoid arthritis (RA) patients express anti-citrullinated protein antibodies (ACPA). Unaffected first-degree relatives of RApatients (FDR) also express ACPA, commonly of the IgA isotype. IgG anti-homocitrullinated/carbamylated protein antibodies (AHCPA) have been detected in both RA and FDR. It is unknown whether other isotypes are expressed. We aim to investigate the AHCPA isotype profile in unaffected FDR of RApatients. METHODS: The enrolled subjects were examined by a rheumatologist. FDR and healthy controls (HC) were excluded if they had swollen joints. Serum AHCPA targeting homocitrullinated fibrinogen was determined using enzyme linked immunoabsorbant assay (ELISA). FDR were genotyped for HLA-DR4 alleles encoding the shared epitope (SE). RESULTS: 125 RA (35 probands), 61 FDR and 40 HC were included. 20% of FDR expressed IgG AHCPA, compared to 30% in RApatients and 5% in HC (p=0.0010 for RA vs. HC). Levels of IgG AHCPA in FDR were similar to RA. FDR rarely expressed IgM (8%) and did not express IgA AHCPA. 20% of RA and 13% of HC subjects expressed IgM, but very few expressed IgA AHCPA (<7% in both groups). AHCPA expression in FDR was not significantly associated with joint symptoms, smoking or SE. CONCLUSIONS: IgG AHCPA is the most commonly expressed isotype in RA and FDR. The significance of IgG AHCPA in FDR is unclear as it was not associated with joint symptoms or other risk factors for RA. Longitudinal studies are needed to determine whether AHCPA is meaningful in populations at risk for RA.
Authors: Katherine Cook; Wei Xue; Suha Atabani; Peter Symonds; Abdullah Al Omari; Ian Daniels; Sabaria Shah; Ruhul Hasan Choudhury; Daisy Weston; Rachael Metheringham; Victoria Brentville; Lindy Durrant Journal: Front Immunol Date: 2022-04-08 Impact factor: 8.786