目的:抗中性粒细胞胞浆抗体(ANCA)是ANCA相关小血管炎(AAV)的重要的血清学标志。既往研究证实ANCA的亲合力与病情密切相关。本实验室的前期工作发现:丙基硫氧嘧啶(PTU)诱发的AAV临床缓解后虽然ANCA持续阳性,但鲜有复发,可能与停药后抗MPO抗体的亲合力迅速下降有关。我们推测:部分原发性AAV患者反复复发可能与血清ANCA在缓解期仍维持较高的亲合力相关。本研究选取了病程中有复发病史的MPO-ANCA持续阳性的原发AAV患者,研究其血清抗MPO抗体亲合力的变化及其与复发的关系。 方法:选取7例抗MPO抗体持续阳性的原发性AAV患者,分别对每个患者初发期、复发期和缓解期的血清进行抗MPO抗体滴度和亲合力的检测。抗MPO抗体亲合力的检测采用抗原抑制性ELISA,亲和常数(aK)等于能够将抗MPO抗体与固相MPO结合力抑制50%所需的液相MPO摩尔浓度的倒数。抗MPO抗体的滴度则通过将血清标本倍比稀释,应用MPO特异的ELISA方法获得。血管炎病情活动度由伯明翰血管炎活动度评分(BVAS)判定。 结果:7例患者初发期、缓解期和复发期的平均BVAS评分分别为17±3.2、 0.57±1.51和16.7±1.8。活动期(初发期和复发期)MPO-ANCA的平均亲和常数(aK)与缓解期无明显差异(aK值取对数后比较:2.42±0.75比1.92±0.96, P=0.216)。患者初发期和缓解期的MPO-ANCA亲合力也无显著变化(P=0.175)。 aK与BVAS水平、复发次数、受累器官数目、Scr或C反应蛋白均没有显著相关性。但是缓解期维持的时间与缓解期的aK密切相关(P=0.036)。患者的BVAS水平和MPO-ANCA滴度未见显著相关性(r=0.398, P>0.05)。 结论:原发性小血管炎患者其血清抗MPO抗体的亲合力在缓解期持续不下降与复发密切相关,间接提示其病因尚未清除。 关键词:抗髓过氧化物酶抗体,血管炎,亲合力,慢性抗原刺激
[Background] Antineutrophil cytoplasmic antibodies (ANCA) are important serologic markers for ANCA-associated vasculitis (AAV). It has been demonstrated that avidity of ANCA is closely associated with disease activity. Our previous studies in propylthiouracil (PTU)-induced AAV revealed that withdrawal of PTU resulted in clinical remission and significant decrease of avidity of PTU-induced myeloperoxidase (MPO)-ANCA. Our speculation is that non-decrease of avidity of MPO-ANCA might be associated with relapses in patients with primary AAV with sustained MPO-ANCA in remission. This study investigated the changes in avidity of MPO-ANCA in sequential sera from some patients with primary AAV with relapses during follow up. [Methods] Sequential sera samples of seven patients with MPO-ANCA-positive vasculitis at their initial onset, remission and relapse were collected. The avidity of MPO-ANCA was assessed by antigen-inhibition ELISA. The titer of MPO-ANCA was determined by a two-fold dilution of sera in MPO specific ELISA. Vasculitis disease activity was assessed by Birmingham Vasculitis Activity Score (BVAS). [Results] The mean BVAS of the 7 patients at initial onset, remission and relapse was 17±3.2, 0.57±1.51 and 16.7±1.8 respectively. The avidity constant (aK) of MPO-ANCA in active phase (including onset and relapse) is not significantly different from that in remission (taking logarithm, 2.42±0.75 vs 1.92±0.96, P=0.216). No significant correlation could be found between aK and the level of BVAS, the number of relapses, the number of organ involvement, serum creatinine, or CRP. However, aK in remission was closely associated with the duration between remission ans relapse (P=0.036). The titer of MPO-ANCA was not significantly different between initial onset and remission. [Conclusion] Sustained avidity of MPO-ANCA in quiescence is closely associated with relapses in patients with primary ANCA-associated vasculitis, which might indicate unremoval of the chronic repeated antigen stimulation. [Key words] ANCA, vasculitis, avidity, myeloperoxidase, antigen stimulation