Gan Ryan W, Demoruelle M Kristen, Deane Kevin D, Weisman Michael H, Buckner Jane H, Gregersen Peter K, Mikuls Ted R, O'Dell James R, Keating Richard M, Fingerlin Tasha E, Zerbe Gary O, Clare-Salzler Michael J, Holers V Michael, Norris Jill M
Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA.
Division of Rheumatology, University of Colorado, Aurora, Colorado, USA.
Ann Rheum Dis. 2017 Jan;76(1):147-152. doi: 10.1136/annrheumdis-2016-209154. Epub 2016 May 17.
Previously, we found that omega-3 fatty acids (n-3 FAs) were inversely associated with anti-cyclic citrullinated peptide (anti-CCP) positivity in participants at risk for future rheumatoid arthritis (RA). We investigated whether n-3 FAs were also associated with rheumatoid factor (RF) positivity and whether these associations were modified by shared epitope (SE) positivity.
The Studies of the Etiology of RA (SERA) cohort includes RA-free participants who are at increased risk for RA. We conducted a nested case-control study (n=136) to determine the association between RF and anti-CCP2 positivity and n-3 FA percentage in erythrocyte membranes (n-3 FA% in red blood cells (RBCs)). Additionally, in the baseline visit of the SERA cohort (n=2166), we evaluated the association between reported n-3 FA supplement use and prevalence of RF and anti-CCP2. We assessed SE positivity as an effect modifier.
In the case-control study, increasing n-3 FA% in RBCs was inversely associated with RF positivity in SE-positive participants (OR 0.27, 95% CI 0.10 to 0.79), but not SE-negative participants. Similar associations were seen with anti-CCP positivity in SE-positive participants (OR 0.42, 95% CI 0.20 to 0.89), but not SE-negative participants. In the SERA cohort at baseline, n-3 FA supplement use was associated with a lower prevalence of RF positivity in SE-positive participants (OR 0.32, 95% CI 0.12 to 0.82), but not SE-negative participants; similar but non-significant trends were observed with anti-CCP2.
The potential protective effect of n-3 FAs on RA-related autoimmunity may be most pronounced in those who exhibit HLA class II genetic susceptibility to RA.
此前,我们发现ω-3脂肪酸(n-3 FAs)与未来有类风湿关节炎(RA)风险的参与者中抗环瓜氨酸肽(抗CCP)阳性呈负相关。我们研究了n-3 FAs是否也与类风湿因子(RF)阳性相关,以及这些关联是否因共享表位(SE)阳性而改变。
RA病因研究(SERA)队列包括有RA风险增加的无RA参与者。我们进行了一项巢式病例对照研究(n = 136),以确定RF和抗CCP2阳性与红细胞膜中n-3 FA百分比(红细胞(RBC)中n-3 FA%)之间的关联。此外,在SERA队列的基线访视中(n = 2166),我们评估了报告的n-3 FA补充剂使用与RF和抗CCP2患病率之间的关联。我们将SE阳性作为效应修饰因素进行评估。
在病例对照研究中,红细胞中n-3 FA%的增加与SE阳性参与者的RF阳性呈负相关(比值比[OR] 0.27,95%置信区间[CI] 0.10至0.79),但与SE阴性参与者无关。在SE阳性参与者中,抗CCP阳性也有类似关联(OR 0.42,95% CI 0.20至0.89),但与SE阴性参与者无关。在基线时的SERA队列中,n-3 FA补充剂的使用与SE阳性参与者中RF阳性的较低患病率相关(OR 0.32,95% CI 0.12至0.82),但与SE阴性参与者无关;抗CCP2有类似但不显著的趋势。
n-3 FAs对RA相关自身免疫的潜在保护作用可能在那些表现出对RA有HLA II类基因易感性的人群中最为明显。