针对多种瓜氨酸化抗原的抗体在类风湿性关节炎患者的关节中富集。

Antibodies to several citrullinated antigens are enriched in the joints of rheumatoid arthritis patients.

作者信息

Snir Omri, Widhe Mona, Hermansson Monika, von Spee Caroline, Lindberg Johan, Hensen Sanne, Lundberg Karin, Engström Ake, Venables Patrick J W, Toes René E M, Holmdahl Rikard, Klareskog Lars, Malmström Vivianne

机构信息

Karolinska University Hospital, Karolinska Institutet at Solna, Stockholm, Sweden.

出版信息

Arthritis Rheum. 2010 Jan;62(1):44-52. doi: 10.1002/art.25036.

DOI:10.1002/art.25036

PMID:20039432

Abstract

OBJECTIVE

High titers of specific anti-citrullinated protein antibodies (ACPAs) are frequently present in the serum of rheumatoid arthritis (RA) patients, but their presence in synovial fluid is less well characterized. The purpose of this study was to compare the levels of antibody to 4 well-defined citrullinated candidate RA autoantigens in serum and synovial fluid and to determine whether antibodies to one citrullinated antigen are dominant over another. Furthermore, we studied their relationships with mutated citrullinated vimentin (MCV), a newly identified RA-specific serum assay, and the classic cyclic citrullinated peptide (CCP) in the synovial fluid of well-defined HLA-DR groups.

METHODS

Paired serum and synovial fluid samples from 290 RA patients and serum samples from 100 age- and sex-matched healthy controls were analyzed for the presence of anti-MCV and anti-CCP antibodies and for reactivity to citrullinated fibrinogen, alpha-enolase, type II collagen, and vimentin. A total of 219 of the 290 patients were genotyped for the HLA-DR shared epitope alleles.

RESULTS

Significantly higher proportions of antibodies against all RA-associated citrullinated antigens were found in synovial fluid as compared with serum. This was also true for the MCV and CCP responses but not for non-RA-associated anti-tetanus toxoid antibodies. As expected, we found a high correlation between citrullinated vimentin and MCV responses. All synovial fluid ACPAs were predominantly associated with HLA-DRB1*04 alleles and were confined to the CCP+/MCV+ subset of patients.

CONCLUSION

MCV and CCP positivity represent a similar subset of RA patients, whereas ACPAs with different fine specificities fall into subgroups of anti-CCP+/anti-MCV+ patients. The levels of all specific ACPAs were elevated in synovial fluid, suggesting that there is local antibody production and/or retention of ACPAs at the site of inflammation governed by RA-predisposing genes.

摘要

目的

类风湿关节炎（RA）患者血清中常存在高滴度的特异性抗瓜氨酸化蛋白抗体（ACPA），但其在滑液中的情况特征描述较少。本研究的目的是比较血清和滑液中针对4种明确的瓜氨酸化RA自身抗原候选物的抗体水平，并确定针对一种瓜氨酸化抗原的抗体是否比另一种更具优势。此外，我们研究了它们与突变瓜氨酸化波形蛋白（MCV，一种新发现的RA特异性血清检测指标）以及明确的HLA-DR组滑液中经典环瓜氨酸肽（CCP）的关系。

方法

分析了290例RA患者的配对血清和滑液样本以及100例年龄和性别匹配的健康对照的血清样本，检测抗MCV和抗CCP抗体的存在情况以及对瓜氨酸化纤维蛋白原、α-烯醇化酶、II型胶原和波形蛋白的反应性。对290例患者中的219例进行了HLA-DR共享表位等位基因的基因分型。

结果

与血清相比，滑液中针对所有RA相关瓜氨酸化抗原的抗体比例显著更高。MCV和CCP反应也是如此，但非RA相关的抗破伤风类毒素抗体则不然。正如预期的那样，我们发现瓜氨酸化波形蛋白和MCV反应之间存在高度相关性。所有滑液ACPA主要与HLA-DRB1*04等位基因相关，并且局限于CCP+/MCV+患者亚组。