Effects of Smoking and Shared Epitope on the Production of Anti–Citrullinated Peptide Antibody in a Japanese Adult Population

Abstract

Objective. Anti-citrullinated peptide antibody (ACPA) and rheumatoid factor (RF) are markers to rheumatoid arthritis (RA). Smoking and shared epitope (SE) in HLA-DRB1 are associated with the production of these autoantibodies in RA. Detailed distribution and characterization of ACPA and RF in the general population have remained unclear. We aimed to evaluate positivity of ACPA and RF in a general Japanese population and to detect correlates, including genetic components. Methods. ACPA and RF were quantified in 9,804 Japanese volunteers ages 30 -75 years. Logistic regression analyses were performed to evaluate the effects of candidates of correlates on the autoantibody positivity. A genome-wide association study (GWAS) was performed using 394,239 single nucleotide polymorphisms for 3,170 participants, and HLA-DRB1 alleles were imputed based on the GWAS data. Results. A total of 1.7% and 6.4% of subjects were positive for ACPA and RF, respectively, and the 2 markers showed a significant correlation (P ‫؍‬ 2.0 ؋ 10 ؊23 ). Old age was associated with ACPA positivity (P ‫؍‬ 0.00062). Sex, smoking, SE, and other candidates of correlates did not have significant effects. Interaction between smoking and SE positivity was not apparent, but smoking showed a significant association with high levels of ACPA (P ‫؍‬ 0.0019). Conclusion. ACPA and RF could be detected in 1.7% and 6.4% of the Japanese adult population without RA, respectively. ACPA and RF were suggested to share mechanisms even in healthy populations. Old age was associated with increasing ACPA positivity. While positivity of ACPA and RF was not associated with SE and smoking, an association between high ACPA and smoking was observed.

Significant association of periodontal disease with anti-citrullinated peptide antibody in a Japanese healthy population – The Nagahama study

“…28 subjects were excluded due to insufficient data. As a result, 9575 subjects in the Nagahama Study who did not have connective tissue diseases [17] were selected for the current study. The details of sample selections were described in the previous study [17].…”

“…As a result, 9575 subjects in the Nagahama Study who did not have connective tissue diseases [17] were selected for the current study. The details of sample selections were described in the previous study [17]. The current study was approved by the Ethics Committee, Kyoto University Graduate School and Faculty of Medicine and written informed consent was obtained from each participant.…”

“…The details of the measurement of ACPA and RF were described previously [17]. Briefly, the 2nd generation anti-CCP antibody was quantified as ACPA by MESACUP CCP ELISA kit (Medical and Biological Laboratories Co., Ltd, Nagoya, Japan).…”

“…Recently, we reported detailed distribution and correlates of ACPA and RF using the data of the Nagahama Study, a Japanese community based prospective cohort [17]. Here, we analyzed the associations between PD status and RA-related autoantibodies especially ACPA using the data of the Nagahama study.…”

Problems of Rheumatoid Arthritis Immunopathology: Evolution of the Disease

“…2). В отличие от больных РА, у здоровых людей, у которых в дальнейшем не наблюдалось развитие РА, выявляется низкий уровень АЦБ с ограниченной реактивностью к небольшому чис-лу цитруллинированных белков [47,48]. Поскольку пос-ле дебюта РА «сероконверсия» АЦБ наблюдается редко [49], это свидетельствует о том, что гиперпродукция ан-тител является «причинным» фактором, а не следствием болезни и рассматривается как важное доказательство существования «преклинической» системной «аутоим-мунной» фазы РА.…”