Immunogenetic Risks of Anti-Cyclical Citrullinated Peptide Antibodies in a North American Native Population with Rheumatoid Arthritis and Their First-degree Relatives
Immunogenetic Risks of Anti-Cyclical Citrullinated Peptide Antibodies in a North American Native Population with Rheumatoid Arthritis and Their First-degree Relatives
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DOI：
10.3899/jrheum.080855
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发表时间：
2009-06-01
影响因子：
3.9
通讯作者：
Oen, Kiem
中科院分区：
文献类型：
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作者：
El-Gabalawy, Hani S.;Robinson, David B.;Oen, Kiem
Objective.确定抗环瓜氨酸肽（抗CCP）抗体在北美本土类风湿关节炎（RA）先证者未受影响亲属中的流行率;以及共有表位（SE）和HLA-DRB 1 *0901与RA和抗CCP抗体的相关性。受试者为RA先证者、受累亲属、未受影响的一级亲属（FDR）和更远的亲属，以及来自同一人群的未受影响的对照。DNA测序法进行HLA-DRB 1分型，ELISA法检测抗CCP抗体。DRB 1 *10901、SE和SE/DRB 1 *0901基因型均与RA相关。SE/DRB 1 *0901基因型与< 16岁的发病年龄相关，而其他SE基因型与< 16岁的发病年龄无关。抗CCP抗体的频率在RA先证者中为82%，在FDR中为17%，在远亲中为11%，在对照中为3%。在未患病亲属中，SE/DRB 1 *0901基因型与抗CCP抗体风险显著增加相关，而与SE无关。非SE等位基因DRB 1 *0901与RA的独立关联在该人群中得到证实，并且该等位基因与SE等位基因的组合与疾病发作的年轻年龄相关。RA先证者FDR的抗CCP抗体患病率高于远亲和无关对照，提示疾病发展的风险梯度。免疫遗传风险可能在疾病发病机制的早期作用于RA自身抗体形成的起始水平;然而，尚不清楚进展为临床疾病涉及哪些额外的遗传和环境风险。（2009年5月1日首次发布; Rheumol 2009;36：1130-5; 10.3899/jrheum.080855）
Objective. To determine the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in unaffected relatives of North American Native probands with rheumatoid arthritis (RA); and the associations of the shared epitope (SE) and HLA-DRB1*0901 with RA and anti-CCP antibodies.Methods. The subjects were RA probands, affected relatives, unaffected first-degree (FDR) and more distant relatives, and unaffected controls from the same population. HLA-DRB1 typing was determined by DNA sequencing and anti-CCP antibodies were determined by ELISA.Results. DRB1*10901, SE, and SE/DRB1*0901 genotypes were all associated with RA. SE/DRB1*0901, but not other SE genotypes, was associated with disease onset at age < 16 years. The frequency of anti-CCP antibodies was 82% in RA probands, 17% in FDR, 11% in more distant relatives, and 3% in controls. Among unaffected relatives, a significant increased risk of anti-CCP was associated with SE/DRB1*0901 genotype, but not with SE.Conclusion. An independent association of the non-SE allele DRB1*0901 with RA was confirmed in this population, and this allele in combination with a SE allele was associated with younger age at disease onset. FDR of RA probands have a higher prevalence of anti-CCP antibodies than more distant relatives and unrelated controls, suggesting a gradient of risk for disease development. Immunogenetic risks may act early in disease pathogenesis at the level of initiation of RA autoantibody formation; however, it is not clear what additional genetic and environmental risks are involved in progression to clinical disease. (First Release May 1 2009; Rheumatol 2009;36:1130-5; 10.3899/jrheum.080855)