The Danish Twin Registry, Epidemiology, Institute of Public Health, University of Southern Denmark, Denmark.
J Autoimmun. 2013 Mar;41:120-5. doi: 10.1016/j.jaut.2012.12.001. Epub 2013 Jan 3.
To assess the genetic effect on the occurrence of rheumatoid arthritis (RA) associated autoantibodies.
A co-twin control study of 27 monozygotic (MZ) and 51 dizygotic same sexed (DZss) RA discordant twins.
The probandwise concordance rate of anti-keratin antibodies (AKA), anti-cyclic citrullinated peptide antibodies (ACPA), IgA- and IgM rheumatoid factor (IgA-RF and IgM-RF). The odds ratio for these autoantibodies based on both conditional and unconditional logistic regression adjusting for the two major genetic risk factors as well as smoking.
The probandwise concordance rates (95% CI) of ACPA, AKA, IgM-RF and IgA-RF were 78.6 (55.4-92.4), 16.7 (0.6-58.4), 30.0 (7.3-60.6), 42.1 (14.5-71.1) in MZ twins and 25.0 (10.3-44.4), 0.0 (0.0-27.7), 10.5 (1.4-31.5) and 22.2 (6.8-45.0) in DZss twins. In twin pairs discordant for both RA and autoantibodies the OR of ACPA, AKA, IgM-RF and IgA-RF was 5 (0.5-236.5) 9 (1.3-394.5) 272 (3.5-593.2) and 10 (1.4-434.0) in MZ twin pairs and 17 (4.4-146.1) 20 (3.2-828.0) 33 (5.5-1342.4) and 577 (7.4-1149.2) in DZss twin pairs. In multiple logistic regression analysis on ACPA, the MZ/DZ OR was 21.1 (3.3-213.5) when adjusting for age, sex, ever smoking, PTPN22 1858 T-allele, Shared Epitope (SE) and SE-smoking interaction.
There is a genetic contribution to ACPA generation independent of both SE and PTPN22 1858 T-allele. Environmental factors may trigger the expression of IgA-RF, ACPA and AKA in healthy persons who are predisposed to RA.
评估遗传因素对类风湿关节炎（RA）相关自身抗体发生的影响。
对 27 对同卵（MZ）和 51 对同性别双卵（DZss）RA 不一致双胞胎进行了双胞胎对照研究。
抗角蛋白抗体（AKA）、抗环瓜氨酸肽抗体（ACPA）、IgA 和 IgM 类风湿因子（IgA-RF 和 IgM-RF）的先证者一致性率。基于条件和非条件逻辑回归，调整两个主要遗传风险因素以及吸烟因素后，这些自身抗体的优势比。
MZ 双胞胎中 ACPA、AKA、IgM-RF 和 IgA-RF 的先证者一致性率（95%CI）分别为 78.6%（55.4-92.4）、16.7%（0.6-58.4）、30.0%（7.3-60.6）和 42.1%（14.5-71.1），DZss 双胞胎中分别为 25.0%（10.3-44.4）、0.0%（0.0-27.7）、10.5%（1.4-31.5）和 22.2%（6.8-45.0）。在同时患有 RA 和自身抗体的双胞胎对中，ACPA、AKA、IgM-RF 和 IgA-RF 的 OR 分别为 5（0.5-236.5）、9（1.3-394.5）、272（3.5-593.2）和 10（1.4-434.0）在 MZ 双胞胎对中，17（4.4-146.1）、20（3.2-828.0）、33（5.5-1342.4）和 577（7.4-1149.2）在 DZss 双胞胎对中。在对 ACPA 进行多因素逻辑回归分析时，当调整年龄、性别、吸烟史、PTPN22 1858T 等位基因、共享表位（SE）和 SE-吸烟相互作用后，MZ/DZ 的 OR 为 21.1（3.3-213.5）。
除了 SE 和 PTPN22 1858T 等位基因之外，遗传因素对 ACPA 的产生也有一定的影响。环境因素可能会在易患 RA 的健康人群中引发 IgA-RF、ACPA 和 AKA 的表达。
