Isotype distribution of anti-cyclic citrullinated peptide antibodies in undifferentiated arthritis and rheumatoid arthritis reflects an ongoing immune response
Isotype distribution of anti-cyclic citrullinated peptide antibodies in undifferentiated arthritis and rheumatoid arthritis reflects an ongoing immune response
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DOI：
10.1002/art.22279
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发表时间：
2006-12-01
影响因子：
--
通讯作者：
Toes, R. E. M.
中科院分区：
文献类型：
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作者：
Verpoort, K. N.;Jol-van der Zijde, C. M.;Toes, R. E. M.
Objective.尚未描述类风湿性关节炎（RA）特异性抗环瓜氨酸肽（抗CCP）抗体应答（通过抗CCP同种型测定）的演变。本研究旨在确定抗CCP同种型在未分化关节炎（UA）患者、近期发作的RA患者和长期RA患者中的使用情况。方法.采用酶联免疫吸附试验检测110例UA患者和152例RA患者关节炎发病早期血清中抗CCP抗体IgG阳性的伊加、IgM和IgG亚类。将1年内发生RA的UA患者（UA -> RA）与1年内未发生RA的UA患者（UA -> UA）进行比较。此外，将从RA患者亚组（n = 64）获得的基线血清样本与从相同患者中位7年后获得的血清进行比较。结果IgM抗CCP存在于UA患者和RA患者的早期样本中，以及RA患者的随访样本中。一些IgG抗CCP抗体阳性的患者在疾病发作后早期没有IgM抗CCP抗体，但在关节炎病程后期显示IgM抗CCP抗体。在早期样本中检测到不同的同种型使用模式，与RA患者相比，UA患者和UA -> UA患者与UA -> RA患者相比，所有抗CCP同种型的频率都有降低的趋势。7年后，除IgG 1外的所有同种型水平均下降。结论这些数据表明抗CCP同种型库在关节炎病程的早期发展到完全使用。IgM抗CCP抗体的持续存在表明新的B细胞持续募集到抗CCP应答中，反映了抗CCP阳性关节炎过程中RA特异性抗CCP应答的持续（再）激活。
Objective. The evolution of the rheumatoid arthritis (RA)-specific anti-cyclic citrullinated peptide (antiCCP) antibody response, as measured by the isotypes of anti-CCP, has not been described. This study was undertaken to determine anti-CCP isotype usage in patients with undifferentiated arthritis (UA), patients with recent-onset RA, and patients with RA of long duration. Methods. IgA, IgM, and IgG subclasses of anti-CCP were measured by enzyme-linked immunosorbent assay in serum samples that were obtained from IgG anti-CCP antibody-positive patients with UA (n = 110) and IgG anti-CCP antibody-positive patients with RA (n = 152) early after the onset of arthritis. Patients with UA in whom RA developed within 1 year (UA -> RA) were compared with patients with UA in whom RA did not develop within 1 year (UA -> UA). In addition, baseline serum samples obtained from a subset of patients with RA (n = 64) were compared with sera obtained from the same patients a median of 7 years later. Results. IgM anti-CCP was present in early samples from both patients with UA and patients with RA and in followup samples from patients with RA. Several IgG anti-CCP antibody-positive patients who did not have IgM anti-CCP early after disease onset did display IgM anti-CCP later in the course of the arthritis. A diverse pattern of isotype usage was detected in early samples, with a trend toward lower frequencies of all isotypes of anti-CCP in patients with UA compared with patients with RA and in UA -> UA patients compared with UA -> RA patients. Levels of all isotypes except IgG1 had decreased after 7 years. Conclusion. These data indicate development of the anti-CCP isotype repertoire into full usage early in the course of arthritis. The sustained presence of IgM anti-CCP indicates ongoing recruitment of new B cells into the anti-CCP response, reflecting a continuous (re)activation of the RA-specific anti-CCP response during the course of anti-CCP-positive arthritis.