Epitope spreading of the anti-citrullinated protein antibody response occurs before disease onset and is associated with the disease course of early arthritis
Epitope spreading of the anti-citrullinated protein antibody response occurs before disease onset and is associated with the disease course of early arthritis
复制标题
DOI：
10.1136/ard.2009.124537
复制
发表时间：
2010-08-01
影响因子：
27.4
通讯作者：
Pruijn, Ger J. M.
中科院分区：
文献类型：
--
作者：
van der Woude, Diane;Dahlqvist, Solbritt Rantapaa;Pruijn, Ger J. M.
抗瓜氨酸化蛋白抗体（ACPA）是类风湿关节炎（RA）发展最具预测性的因素。目的通过研究从关节炎发病前到长期RA的整个病程中采集的血清样本中ACPA的精细特异性，探讨瓜氨酸表位的识别是否在疾病发生或进展过程中发生变化。方法采用酶联免疫吸附法测定5种不同瓜氨酸化抗原的抗体。采用36例在发病前和发病后献血的患者的血清样本，探讨发病前瓜氨酸抗原识别的发展情况。使用抗环瓜氨酸肽-2 （CCP2）阳性的未分化性关节炎（UA）患者的血清研究ACPA反应性与疾病结局的关系，这些患者已经或没有进展为RA （UA-RA n = 81, UA-UA n = 35）。为了研究长期以来RA患者的ACPA识别谱，将68名患者的基线血清样本与7年后获得的样本进行了比较。结果在发病前，可识别的瓜氨酸肽数量增加。在疾病表现时，后来发展为RA的UA患者比UA-UA患者识别的肽明显更多。在病程的后期，ACPA精细特异性没有改变。结论在RA发病前，随着瓜氨酸化抗原识别的增加，表位扩展发生。UA-UA患者和UA-RA患者在ACPA精细特异性的免疫学差异存在于基线，并与未来的疾病病程相关。
Background Anti-citrullinated protein antibodies (ACPA) are the most predictive factor for the development of rheumatoid arthritis (RA).Objective To investigate whether the recognition of citrullinated epitopes changes during disease onset or progression, by studying the fine specificity of ACPA in serum samples collected throughout the disease course, from before the onset of arthritis to longstanding RA.Methods Antibodies recognising five distinct citrullinated antigens were determined by enzyme-linked immunosorbent assay. Serum samples from 36 individuals who had donated blood before and after disease manifestation were used to investigate the development of citrullinated antigen recognition before disease onset. The association of ACPA reactivities with disease outcome was studied using sera from anti-cyclic citrullinated peptide-2 (CCP2)-positive patients with undifferentiated arthritis (UA) who did or did not progress to RA (UA-RA n = 81, or UA-UA n = 35). To investigate the ACPA recognition profile in patients with RA over a prolonged period of time, baseline serum samples from 68 patients were compared with samples obtained 7 years later.Results The number of recognised citrullinated peptides increased in the period preceding disease onset. At the time of disease manifestation, patients with UA who later developed RA recognised significantly more peptides than UA-UA patients. At later stages of the disease course, the ACPA fine specificity did not change.Conclusion Epitope spreading with an increase in the recognition of citrullinated antigens occurs before the onset of RA. Immunological differences in ACPA fine specificity between UA-UA patients and UA-RA patients are present at baseline and are associated with the future disease course.