Department of Medicine, Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Beijing, China.
Rheumatology (Oxford). 2010 Nov;49(11):2068-75. doi: 10.1093/rheumatology/keq203. Epub 2010 Jul 31.
ANCAs with specificity for MPO are serological markers of ANCA-associated vasculitides, especially microscopic polyangiitis (MPA). This study investigated potential associations between the influence of MPO-ANCA on the oxidation activity of MPO and the clinical manifestations as well as immunological characteristics of MPO-ANCA.
MPO-ANCA was purified with MPO-affinity chromatography from plasma of 13 consecutive patients with MPO-ANCA-positive MPA. The titre, avidity, immunoglobulin G (IgG) subclasses and the ability to reverse the binding between ceruloplasmin and MPO of MPO-ANCA were tested using ELISA. The oxidation activity of MPO in the presence of MPO-ANCA was measured. The associations between the oxidation activity of MPO after binding MPO-ANCA and the clinical and immunological characteristics of MPO-ANCA were analysed.
The MPO activity without binding to its autoantibodies was 1.521 (0.12) (expressed by A-values at 10 min, using o-phenylenediamine as substrate). After binding affinity-purified MPO-ANCA, the MPO activity ranged from 1.083 to 1.642. Correlation analysis showed that the oxidation activity of MPO after binding MPO-ANCA positively correlated with the level of ceruloplasmin binding on MPO in presence of MPO-ANCA (r = 0.617, P = 0.025) and negatively correlated with initial sera creatinine levels (r = -0.564, P = 0.045), BVAS (r = -0.735, P = 0.004), avidity of MPO-ANCA (r = -0.575, P = 0.040), levels of IgG2 (r = -0.610, P = 0.027) and IgG3 subclasses (r = -0.695, P = 0.008) of MPO-ANCA.
MPO-ANCA from different patients can influence MPO activity with different levels. The low oxidation activity of MPO after binding MPO-ANCA might be associated with more severe disease.
抗髓过氧化物酶抗体（MPO-ANCA）特异性针对 MPO，是抗中性粒细胞胞质抗体（ANCA）相关血管炎的血清学标志物，尤其是显微镜下多血管炎（MPA）。本研究旨在探讨 MPO-ANCA 对 MPO 氧化活性的影响与 MPO-ANCA 的临床表现和免疫学特征之间的潜在关联。
采用 MPO 亲和层析法从 13 例 MPO-ANCA 阳性 MPA 患者的血浆中纯化 MPO-ANCA。采用 ELISA 法检测 MPO-ANCA 的效价、亲和力、免疫球蛋白 G（IgG）亚类以及逆转铜蓝蛋白与 MPO 结合的能力。检测 MPO-ANCA 结合 MPO 后 MPO 氧化活性。分析 MPO 与 MPO-ANCA 结合后氧化活性与 MPO-ANCA 的临床和免疫学特征之间的相关性。
未与自身抗体结合的 MPO 活性为 1.521（0.12）（以邻苯二胺为底物，10 分钟时的 A 值表示）。结合亲和纯化的 MPO-ANCA 后，MPO 活性范围为 1.083 至 1.642。相关性分析表明，MPO 与 MPO-ANCA 结合后的氧化活性与 MPO-ANCA 存在时铜蓝蛋白与 MPO 的结合水平呈正相关（r = 0.617，P = 0.025），与初始血清肌酐水平呈负相关（r = -0.564，P = 0.045），与 BVAS（r = -0.735，P = 0.004）、MPO-ANCA 的亲和力（r = -0.575，P = 0.040）、IgG2（r = -0.610，P = 0.027）和 IgG3 亚类（r = -0.695，P = 0.008）呈负相关。
来自不同患者的 MPO-ANCA 可以以不同的水平影响 MPO 活性。MPO-ANCA 结合后 MPO 氧化活性较低可能与疾病更严重有关。
