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丙硫氧嘧啶诱导的抗中性粒细胞胞浆抗体相关血管炎患者血清中抗髓过氧化物酶IgG亚类分布及亲和力

Anti-myeloperoxidase IgG subclass distribution and avidity in sera from patients with propylthiouracil-induced antineutrophil cytoplasmic antibodies associated vasculitis.

作者信息

Gao Ying, Ye Hua, Yu Feng, Guo Xiao-Hui, Zhao Ming-Hui

机构信息

Department of Nephrology, Peking University First Hospital, Beijing, PR China.

出版信息

Clin Immunol. 2005 Oct;117(1):87-93. doi: 10.1016/j.clim.2005.06.002.

Abstract

OBJECTIVE

Propylthiouracil (PTU) could induce MPO-ANCA-positive vasculitis. The aim of this study was to compare the IgG subclass distribution and avidity of MPO-ANCA in sera from patients with primary ANCA-associated vasculitis (AASV) and PTU-induced vasculitis.

METHODS

Nineteen patients with primary AASV with MPO-ANCA and thirteen patients with PTU-induced vasculitis were enrolled in the current study. Sera in both active phase and remission were collected. Anti-MPO IgG subclasses were detected by antigen specific ELISAs using specific monoclonal antibodies as second antibodies, and MPO-ANCA avidity was assessed by antigen-inhibition ELISAs.

RESULTS

In primary AASV, all four anti-MPO IgG subclasses could be detected in active phase with IgG1 (100%), IgG2 (73.7%), IgG3 (63.2%) and IgG4 (94.7%), and in remission, IgG1 and IgG4 subclasses in most patients remained positive. However, in PTU-induced vasculitis, anti-MPO IgG3 subclass could not be detected, the anti-MPO IgG subclasses in active phase were IgG1 (100%), IgG2 (61.5%) and IgG4 (46.2%). Furthermore, five out of the six patients (88.8%) with PTU-induced vasculitis with positive IgG4 subclass in active phase turned to negative in remission, however, only eight out of the fourteen patients (57.1%) with primary AASV turned to negative. The median avidity constant of MPO-ANCA was 56 (8.96 to >140) x 10(7) mol/l for patients with primary AASV and 0.7 (<0.28 to >140) x 10(7) mol/l for patients with PTU-induced vasculitis respectively. Furthermore, the relative levels of MPO-ANCA avidity were associated with elevation of ESR in primary AASV and were associated with BVAS scores in patients with PTU-induced vasculitis, respectively.

CONCLUSION

MPO-ANCA IgG subclass distribution and avidity were different between patients with primary AASV and PTU-induced vasculitis. It was suggested that the mechanism of ANCA production in PTU-induced vasculitis was different from that in primary AASV, and the avidity of MPO-ANCA might be associated with disease activity.

摘要

目的

丙硫氧嘧啶(PTU)可诱发髓过氧化物酶抗中性粒细胞胞浆抗体(MPO-ANCA)阳性血管炎。本研究旨在比较原发性抗中性粒细胞胞浆抗体相关性血管炎(AASV)患者和PTU诱发的血管炎患者血清中MPO-ANCA的IgG亚类分布及亲和力。

方法

本研究纳入19例原发性AASV伴MPO-ANCA患者和13例PTU诱发的血管炎患者。收集活动期和缓解期的血清。使用特异性单克隆抗体作为二抗,通过抗原特异性酶联免疫吸附测定(ELISA)检测抗MPO IgG亚类,并通过抗原抑制ELISA评估MPO-ANCA的亲和力。

结果

在原发性AASV中,活动期可检测到所有四种抗MPO IgG亚类,IgG1(100%)、IgG2(73.7%)、IgG3(63.2%)和IgG4(94.7%),缓解期大多数患者的IgG1和IgG4亚类仍为阳性。然而,在PTU诱发的血管炎中,未检测到抗MPO IgG3亚类,活动期抗MPO IgG亚类为IgG1(100%)、IgG2(61.5%)和IgG4(46.2%)。此外,活动期IgG4亚类阳性的PTU诱发的血管炎患者中,6例中有5例(88.8%)在缓解期转为阴性,而原发性AASV患者中14例仅有8例(57.1%)转为阴性。原发性AASV患者MPO-ANCA的中位亲和力常数分别为56(8.96至>140)×10⁷mol/L,PTU诱发的血管炎患者为0.7(<0.28至>140)×10⁷mol/L。此外,原发性AASV中MPO-ANCA亲和力的相对水平与红细胞沉降率(ESR)升高相关,PTU诱发的血管炎患者中与伯明翰血管炎活动评分(BVAS)相关。

结论

原发性AASV患者和PTU诱发的血管炎患者的MPO-ANCA IgG亚类分布及亲和力不同。提示PTU诱发的血管炎中ANCA产生的机制与原发性AASV不同,且MPO-ANCA的亲和力可能与疾病活动有关。

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