Are serum C3 levels or kidney C3 deposits useful markers for predicting outcomes in patients with ANCA-associated vasculitis?

IF 4.7 Q2 IMMUNOLOGY
Alexis Cassard , Clément Kounde , Laurence Bouillet , Tiphaine Goulenok , David Ribes , Rafik Mesbah , Vincent Langlois , Audrey Delas , Françoise Fortenfant , Sébastien Humbert , Céline Lebas , Julie Belliere , Philippe Kerschen , Dominique Chauveau , Magali Colombat , Stanislas Faguer
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Abstract

Introduction

Complement activation emerged as a key actor of anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV). Whether serum levels of C3 (sC3) or C3 kidney deposition may help to refine the prognosis of AAV remains elusive.

Methods

Retrospective multicentric study that included 154 patients with a first flare of AAV and sC3 (n = 143) or C3 kidney staining (n = 95) available at diagnosis. Clinical presentations, kidney pathology, and survival of patients with normal or low sC3 were compared using univariate analyses, Kaplan-Maier curves with log-rank comparison, or multivariate Cox’ model, as appropriate.

Results

20 patients (14 %) had low sC3. sC3 (as bivariate low/normal or as a continuous variable) was associated with 5-year mortality but not with kidney survival. C3 kidney deposition (C3+) was identified in 23 patients who were characterized by more frequent chronic hypertension and lower eGFR at presentation (p = 0.04). C3+ correlated with IgG, IgM, C1q deposition (p = 0.07, p < 0.0001 and p = 0.003, respectively). Chronicity and activity scores were similar in C3+ and C3- patients. Among C3+ patients, those with C3 deposition ≥2+ had lower eGFR at presentation (p = 0.006) and were more frequently classified as sclerotic using the Berden classification (p = 0.04) and as ‘high risk’ using the Brix score (p = 0.03). However, eGFR improvement following induction regimen was similar between C3+ and C3- patients, and kidney survival at 5 years was similar.

Conclusions

Correlation of sC3 with mortality confirms mechanistic links between complement pathways and AAV, but the lack of clear predictive sC3 cut-off and the similar kidney outcome irrespective of C3 deposition precludes their use as biomarkers of AAV outcomes and response to treatment.

血清C3水平或肾脏C3沉积是预测anca相关性血管炎患者预后的有用指标吗?
补体活化是抗中性粒细胞细胞质抗体相关血管炎(AAV)的关键因素。血清C3 (sC3)或C3肾沉积水平是否有助于改善AAV的预后尚不明确。方法回顾性多中心研究,纳入154例诊断时首次出现AAV和sC3 (n = 143)或C3肾脏染色(n = 95)的患者。临床表现、肾脏病理和正常或低sC3患者的生存比较采用单因素分析、Kaplan-Maier曲线和log-rank比较,或多因素Cox模型(视情况而定)。结果低sC3患者20例(14%)。sC3(作为双变量低/正常或作为连续变量)与5年死亡率相关,但与肾脏生存无关。在23例以更频繁的慢性高血压和较低的eGFR为特征的患者中发现C3肾沉积(C3+) (p = 0.04)。C3+与IgG、IgM、C1q沉积相关(p = 0.07, p <0.0001和p = 0.003)。C3+和C3-患者的慢性和活动性评分相似。在C3+患者中,C3沉积≥2+的患者在就诊时eGFR较低(p = 0.006),使用Berden分级(p = 0.04)和Brix评分(p = 0.03)更常被分类为硬化。然而,诱导方案后eGFR改善在C3+和C3-患者之间相似,5年肾脏生存期相似。结论:sC3与死亡率的相关性证实了补体途径与AAV之间的机制联系,但缺乏明确的预测sC3截止点和与C3沉积无关的类似肾脏结果,阻碍了它们作为AAV结局和治疗反应的生物标志物的使用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Translational Autoimmunity
Journal of Translational Autoimmunity Medicine-Immunology and Allergy
CiteScore
7.80
自引率
2.60%
发文量
33
审稿时长
55 days
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