BackgroundRheumatoid Arthritis (RA) is the most prevalent chronic inflammatory arthritis, affecting 0.5-1% worldwide population and predominates in females. Altered fertility has been reported due to a decrease in ovarian reserve secondary to sustained inflammation. The anti-Müllerian Hormone (AMH) is currently the most reliable biomarker of ovarian reserve. However, few and contradictory studies have been reported to analyze the relationship between fertility in RA women patients and AMH.ObjectivesThe aim of present study is to determine the AMH serum concentrations in a long-standing RA patients and control group. We also sought to determine the correlation between AMH serum levels and disease activity measured by different parameters and the effect of biological DMARDs.MethodsSerum AMH levels were measured in 60 women with long-standing RA aged 20-50 y.o. and compared to 59 healthy women. AMH was assessed by ELISA (Gen II Beckman Coulter Inc.) and a large data set of clinical and molecular data was annotated. Demographic parameters, RA disease activity measured by DAS28 score and inflammatory biomarkers such as ESR, CRP, lymphocyte CD4+, CD8+, NK cells, IL-10 and IL-6 were determined. A comprehensive gynecological self-administered questionnaire was given. Serum AMH levels were age-correlated. Differences between groups were calculated using Student’s t-test or Mann-Whitney U test for continuous variables and Fisher’s exact test for categorical variables. Multivariate analysis was conducted by the partial correlation coefficient. Linear regression analysis was performed to study the effect of different variables on proportional AMH change. P value <0.005 were considered significant.ResultsThe median age was similar in AR and control groups (37.4±6.23 vs 37.3±6.27 P=0.937). Mean disease duration was 8.37±5.36 years. The number of previous treatments was <3 in 71.7% of patients and ≥3 in 28.3%. Disease activity measured by DAS28 was 2.89± 1.54. The age-adjusted mean serum concentration of HAM was 1.27 ng/ml [IQR 0.42; 2.24] in RA patients and 1.31 ng/ml [IQR 0.46; 3.09] in controls (P=0.608). Neither disease activity (P=0.862), nor current or previous bDMARDs treatments (P=0.871) were associated with HAM levels. However, a negative linear correlation was observed between HAM and IL-10 levels (P= 0.033).ConclusionOur study shows that ovarian reserve determined by HAM serum levels is not reduced in rheumatoid arthritis patients compared with healthy controls. In our series, HAM levels were not affected by disease activity however a significant correlation was observed between HAM and IL-10 levels. These results support the role of cytokines profile in the female reproductive system and will focus further investigations in this critical area, mainly once biological DMARDs have be recommended in RA pregnant patients.References[1] Brouwer J, Fleurbaaij R, Hazes JM, Dolhain RJ, Laven JS. Subfertility in rheumatoid arthritis is often unexplained or caused by anovulation. Arthritis Care Res (Hoboken). 2016.[2] Brouwer J,...

Background: In rheumatoid arthritis (RA), cigarette smoking affects both rheumatoid factor (RF) and anti-citrullinated cyclic peptide/protein antibody (ACPA) formation, but its association in relation to HLA-DRB1 alleles, especially shared epitope (SE) alleles, have been controversial among different races 1-5 . Furthermore, the impact of cigarette smoking and its cessation on levels of RF and ACPA have not been well documented. Objectives: To investigate the impact of cigarette smoking and cessation on RF and ACPA levels in relation to HLA-DRB1 alleles in the largest RA cohorts in Asians. Methods: A total of 6,239 subjects from two independent Japanese cohorts were enrolled. Their precise smoking histories both before and after the onset of RA were collected in questionnaires. The latest RF and ACPA levels were used (mean disease duration 15.6 years). We defined top quadrant of levels of RF or ACPA as high levels. Associations between smoking status and positivities or high levels of ACPA or RF as well as effects of HLA-DRB1 alleles on the associations were investigated by multiple logistic regression models.Results: Smoking at onset was an independent risk of not only RF and ACPA positivities (RF, odds ratio (OR) 1.52, 95% confidence interval (CI) 1.26-1.85, p=1.8x10 -5 ; ACPA, OR 1.39, 95%CI 1.09-1.76, p=6.8x10 -3 ), but also high levels of these autoantibodies, especially RF (OR 2.06, 95% CI 1.70-2.48, p=7.4x10 -14 ; ACPA OR 1.29, 95%CI 1.06-1.57, p=1.2x10 -2 ). The larger ORs of RF than ACPA suggests that RF is more sensitive to cigarette smoking than ACPA. The effects of cigarette smoking were significantly larger in males than in females. The patients who quited smoking before onset had no longer significant risks of high autoantibody levels compared to subjects who had never smoked (RF, OR 1.33, p=0.099; ACPA, OR 1.19, p=0.093), and the risk was gradually attenuated depending on cessation years (RF, 0-10 years OR 1.34, 10-20 years OR 1.31, > 20 years OR 0.97; ACPA, 0-10 years OR 1.38, 10-20 years OR 1.01, > 20 years OR 1.12). The effect of smoking on ACPA positivity and its high level was apparent only in the presence of SE alleles, while the effect on RF positivity and its high level was apparent despite the presence of SE alleles (Table below). Conclusion: Cigarette smoking especially at RA onset is a significant risk of future high levels of ACPA and RF preferentially in males, and RF is more sensitive to smoking status than ACPA. The effect on ACPA is apparent only in the presence of SE alleles, indicating that an interaction between cigarette smoking and SE alleles affects ACPA formation. On the other hand, the effect of cigarette smoking on RF formation may be independent of SE alleles. Our study imply a novel potential mechanism of RA pathogenesis.