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对体外产生的抗蛋白酶3抗中性粒细胞胞浆抗体进行前瞻性监测并不能改善显微镜下多血管炎的复发预测。

Prospective monitoring of in vitro produced PR3-ANCA does not improve relapse prediction in granulomatosis with polyangiitis.

作者信息

Land Judith, Abdulahad Wayel H, Arends Suzanne, Sanders Jan-Stephan F, Stegeman Coen A, Heeringa Peter, Rutgers Abraham

机构信息

Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

出版信息

PLoS One. 2017 Aug 3;12(8):e0182549. doi: 10.1371/journal.pone.0182549. eCollection 2017.

Abstract

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.

摘要

目的

肉芽肿性多血管炎(GPA)患者易于疾病复发。目前,尚无良好的生物标志物可预测个体患者的复发情况。本研究旨在确定是否可基于体外自身抗体产生增加来区分有复发风险的患者。

方法

对84例蛋白酶3(PR3)抗中性粒细胞胞浆抗体(ANCA)阳性的GPA门诊患者进行了长达两年的前瞻性监测,并纳入了32名健康对照者。定期分离外周血单个核细胞,进行培养,并测定总IgG及PR3-ANCA特异性IgG的体外产生情况。此外,通过间接免疫荧光法测定血清ANCA滴度。

结果

16例患者(21%)在随访期间复发。在纳入时,复发患者与未复发患者之间的ANCA产生无显著差异。与未复发患者的纳入样本相比,复发前样本的血清ANCA滴度及体外PR3-ANCA IgG水平升高。在评估随时间的变化时,与未复发患者的1年随访相比,复发前观察到血清ANCA滴度升高。与未复发患者相比,复发前体外PR3-ANCA水平无显著变化。

结论

虽然复发患者与未复发患者的血清ANCA滴度存在差异,但监测体外PR3-ANCA IgG产生并不能改善GPA患者的复发预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96de/5542648/e0b8836888ca/pone.0182549.g001.jpg

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