Prospective monitoring of <i>in vitro</i> produced PR3-ANCA does not improve relapse prediction in granulomatosis with polyangiitis

Objectives Patients with granulomatosis with polyangiitis (GPA) are prone to disease relapse. Currently, no good biomarkers are available to predict relapses in individual patients. This study aimed to determine whether patients at risk for relapse can be distinguished based on increased in vitro autoantibody production. Methods Eighty-four proteinase 3 (PR3) anti-neutrophil cytoplasmic antibody (ANCA) positive GPA outpatients were prospectively monitored for up to two years and 32 healthy controls were included. At periodic intervals peripheral blood mononuclear cells were isolated, cultured and in vitro production of total and PR3-ANCA-specific IgG was determined. Moreover, serum ANCA titers were measured by indirect immunofluorescence. Results Sixteen patients (21%) relapsed during the follow-up period. At time of inclusion no significant differences were present for ANCA production between relapsing and non-relapsing patients. Samples before relapse exhibited increased serum ANCA titers and in vitro PR3-ANCA IgG levels compared with inclusion samples from non-relapsing patients. When evaluating changes over time, increasing serum ANCA titers were observed prior to relapse compared to a 1-year follow-up from non-relapsing patients. No significant change in in vitro PR3-ANCA levels occurred prior to relapse, compared to non-relapse patients. Conclusions While differences were observed for the serum ANCA titer in relapsing and non-relapsing patients, monitoring in vitro PR3-ANCA IgG production does not improve relapse prediction in GPA patients.研究目的 肉芽肿性多血管炎（Granulomatosis with Polyangiitis, GPA）患者易出现疾病复发，目前尚无有效的生物标志物可用于预测个体患者的复发风险。本研究旨在探讨能否通过体外自身抗体生成量升高来区分复发风险较高的患者。 研究方法 本研究纳入84例蛋白酶3（Proteinase 3, PR3）抗中性粒细胞胞浆抗体（Anti-neutrophil Cytoplasmic Antibody, ANCA）阳性的肉芽肿性多血管炎门诊患者，对其进行长达2年的前瞻性随访，并纳入32名健康对照。定期采集外周血单个核细胞进行分离培养，检测体外总IgG及PR3-ANCA特异性IgG的生成量；同时采用间接免疫荧光法检测血清ANCA滴度。 研究结果 16例患者（21%）在随访期内出现疾病复发。入组时，复发患者与非复发患者的ANCA生成量无显著差异。相较于非复发患者的入组样本，复发前样本的血清ANCA滴度及体外PR3-ANCA IgG水平均有所升高。动态分析随访变化时，与非复发患者的1年随访结果相比，复发前患者的血清ANCA滴度呈升高趋势；而与非复发患者相比，复发前患者的体外PR3-ANCA水平未出现显著变化。 研究结论 尽管复发与非复发患者的血清ANCA滴度存在差异，但体外PR3-ANCA IgG生成量的监测并不能提升肉芽肿性多血管炎患者的复发预测效能。