Liu Li-Jun, Chen Min, Yu Feng, Zhao Ming-Hui, Wang Hai-Yan
Renal Division, Department of Medicine Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.
Nephrology (Carlton). 2008 Oct;13(7):629-35. doi: 10.1111/j.1440-1797.2008.00976.x. Epub 2008 Sep 3.
Our previous study suggested that patients with MPO-ANCA (myeloperoxidase antineutrophil cytoplasmic autoantibodies)-positive Wegener's granulomatosis (WG) were common in Chinese, indicating that patients with MPO-ANCA could manifest as either WG or microscopic polyangiitis (MPA). The aim of this study was to compare the immunological characteristics of MPO-ANCA in patients with WG and MPA.
Fifteen patients with WG and 21 patients with MPA were enrolled in the current study. Anti-MPO IgG subclasses and their titres were detected by antigen-specific enzyme-linked immunosorbent assays (ELISA); affinity was assessed by antigen-inhibition ELISAs. The sera from all patients were employed to inhibit biotin conjugated affinity-purified human anti-MPO antibodies (Probe-biotin), from plasma exchange of a patient with MPA, in a competitive inhibition ELISAs system.
All four anti-MPO subclasses could be detected in sera from patients with WG and MPA. The titres of anti-MPO IgG4 subclass in patients with WG were significantly higher than those with MPA (1:1878 vs 1:218, P < 0.005). The affinity constants of MPO-ANCA were comparable between patients with WG and MPA (0.3-70/M vs 0.3-140/M respectively). Eleven out of the 15 sera and 18 out of the 21 sera could inhibit the binding of the Probe-biotin in patients with WG and MPA respectively. The average inhibition rate was 47.7% +/- 11.5% and 61.7% +/- 14.5% respectively (P < 0.05).
MPO-ANCA IgG4 subclass might play a role in the development of WG. The MPO-ANCA in WG and MPA might recognize overlapping but different epitopes on native MPO molecule. The difference in immunological characteristics of MPO-ANCA might contribute to different disease entities.
我们之前的研究表明,髓过氧化物酶抗中性粒细胞胞浆抗体(MPO-ANCA)阳性的韦格纳肉芽肿(WG)患者在中国较为常见,这表明MPO-ANCA阳性患者可表现为WG或显微镜下多血管炎(MPA)。本研究的目的是比较WG和MPA患者中MPO-ANCA的免疫学特征。
本研究纳入了15例WG患者和21例MPA患者。通过抗原特异性酶联免疫吸附试验(ELISA)检测抗MPO IgG亚类及其滴度;通过抗原抑制ELISA评估亲和力。在竞争性抑制ELISA系统中,使用所有患者的血清抑制来自一名MPA患者血浆置换的生物素偶联亲和纯化人抗MPO抗体(Probe-生物素)。
在WG和MPA患者的血清中均可检测到所有四种抗MPO亚类。WG患者抗MPO IgG4亚类的滴度显著高于MPA患者(1:1878对1:218,P<0.005)。WG和MPA患者中MPO-ANCA的亲和常数相当(分别为0.3-70/M对0.3-140/M)。15例WG患者中的11例血清和21例MPA患者中的18例血清分别可抑制Probe-生物素的结合。平均抑制率分别为47.7%±11.5%和61.7%±14.5%(P<0.05)。
MPO-ANCA IgG4亚类可能在WG的发病中起作用。WG和MPA中的MPO-ANCA可能识别天然MPO分子上重叠但不同的表位。MPO-ANCA免疫学特征的差异可能导致不同的疾病实体。