Greater prevalence of seropositivity for anti-cyclic citrullinated peptide antibody in unaffected first-degree relatives in multicase rheumatoid arthritis-affected families.
OBJECTIVE
This study determined the prevalence and determinants of seropositivity for rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and anti-mutated citrullinated vimentin (anti-MCV) antibody in unaffected first-degree relatives (FDRs) of rheumatoid arthritis (RA) patients.


METHODS
A total of 337 subjects (135 with RA and 202 FDRs) were enrolled in this case-control study. Serum RF, anti-CCP antibody, and anti-MCV antibody were assayed. Subjects in multicase families (≥ 2 affected FDRs within the same family) were identified. Multivariate logistic regression analysis was used to identify risk factors associated with RA-related autoantibodies.


RESULTS
Seropositivity for RF, anti-CCP antibody, or anti-MCV antibody was detected in 14.4%, 5.0%, or 13.4% of unaffected FDRs, respectively. Anti-CCP antibody seropositivity was more prevalent in FDRs in multicase families (17.8%) than in those not in multicase families (1.3%, p < 0.0001). Significant correlations between RA-associated autoantibodies were detected in the FDR group (between RF and anti-CCP antibody: r = 0.366, p < 0.0001; between RF and anti-MCV antibody: r = 0.343, p < 0.0001; and between anti-CCP antibody and anti-MCV antibody: r = 0.849, p < 0.0001). After adjustment for age and sex, anti-CCP antibody seropositivity in FDRs was significantly associated with being in a multicase family (odds ratio, 49.8; 95% confidence interval, 5.6 to 441.6).


CONCLUSIONS
The association between anti-CCP antibody seropositivity in unaffected FDRs and being in a multicase family suggests that genetic and/or environmental factors may increase the risk for RA development in unaffected FDRs.
Department of Internal Medicine, Arthritis and Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu, Korea.
Seong-Kyu
SK
Kim
Jisuk
J
Bae
Hwajeong
H
Lee
Ji Hun
JH
Kim
Sung-Hoon
SH
Park
Jung-Yoon
JY
Choe
D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010375:Pedigree; D010456:Peptides, Cyclic / Q000276:immunology*; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D014746:Vimentin / Q000276:immunology; D055815:Young Adult
D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; D014746:Vimentin; C487763:cyclic citrullinated peptide
Citrullinated antigen; First-degree relative; Rheumatoid arthritis; Rheumatoid factor