Barra Lillian, Scinocca Mathias, Saunders Sheri, Bhayana Rajesh, Rohekar Sherry, Racapé Maud, Coles Robert, Cairns Ewa, Bell David A
St. Joseph's Health Care London and Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
Arthritis Rheum. 2013 Jun;65(6):1439-47. doi: 10.1002/art.37911.
First-degree relatives (FDRs) of rheumatoid arthritis (RA) patients sharing genetic and environmental risk factors for RA may represent a pre-RA state. Since anti-cyclic citrullinated protein/peptide antibodies (ACPAs) appear years before the onset of RA, the purpose of this study was to determine the prevalence of various ACPAs in FDRs of RA patients.
We evaluated 88 RA patients, 50 unaffected FDRs, and 20 healthy control subjects. Six different types of ACPAs were determined by enzyme-linked immunosorbent assay. Joint and periodontal disease symptoms were self-reported. Patients and FDRs were HLA typed for the shared epitope (SE) and the RA-protective alleles HLA-DRB*1301/1302.
FDRs had a high prevalence of ACPAs (48%) as compared to controls (10%). Prevalence of the SE and smoking in FDRs was also high (62% and 49%, respectively). Of all of the ACPAs in the FDRs, 13 of 32 (41%) were of the IgA isotype. The most commonly expressed IgG ACPA targeted citrullinated vimentin, occurring in 20% of FDRs. The FDRs had an average of 1 type of ACPA, whereas the RA patients expressed a median of 5 different ACPAs. The only FDR to later develop RA expressed 4 different ACPAs. Joint and periodontal disease symptoms in the FDRs were significantly associated with smoking (OR 5.714 [95% confidence interval (95% CI) 1.151-28.3] and OR 12.25 [95% CI 2.544-58.99], respectively), but not with ACPAs.
The rate of ACPA positivity in unaffected FDRs of RA patients with a high prevalence of the SE and smoking was 48%, whereas ACPAs were rare in the healthy controls. ACPAs in the FDRs of RA patients was most commonly of the IgA isotype, but IgG ACPA targeting citrullinated vimentin was also frequently found.
类风湿关节炎（RA）患者的一级亲属（FDRs）共享RA的遗传和环境风险因素，可能代表一种RA前期状态。由于抗环瓜氨酸化蛋白/肽抗体（ACPAs）在RA发病前数年就已出现，本研究的目的是确定RA患者FDRs中各种ACPAs的患病率。
我们评估了88例RA患者、50名未受影响的FDRs和20名健康对照者。通过酶联免疫吸附测定法测定六种不同类型的ACPAs。关节和牙周疾病症状由患者自行报告。对患者和FDRs进行共享表位（SE）和RA保护等位基因HLA-DRB*1301/1302的HLA分型。
与对照组（10%）相比，FDRs中ACPAs的患病率较高（48%）。FDRs中SE和吸烟的患病率也较高（分别为62%和49%）。在FDRs的所有ACPAs中，32种中有13种（41%）为IgA同种型。最常见的IgG ACPA靶向瓜氨酸化波形蛋白，在20%的FDRs中出现。FDRs平均有1种类型的ACPAs，而RA患者表达的不同ACPAs中位数为5种。唯一后来发展为RA的FDR表达了4种不同的ACPAs。FDRs中的关节和牙周疾病症状与吸烟显著相关（分别为OR 5.714 [95%置信区间（95%CI）1.151 - 28.3]和OR 12.25 [95%CI 2.544 - 58.99]），但与ACPAs无关。
SE和吸烟患病率高的RA患者未受影响的FDRs中ACPA阳性率为48%，而健康对照者中ACPA罕见。RA患者FDRs中的ACPAs最常见为IgA同种型，但也经常发现靶向瓜氨酸化波形蛋白的IgG ACPA。
