Zickert Agneta, Grönwall Caroline, Juto Anna, Diaz-Gallo Lina-Marcela, Zargar Sepehr Sarrafzadeh, Mongan Ann, Kroon Henk-Andre, Martin Myriam, Blom Anna M, Chang Edmund, Gunnarsson Iva
Division of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Stockholm, Sweden.
Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
Rheumatology (Oxford). 2025 Aug 1;64(8):4825-4833. doi: 10.1093/rheumatology/keaf160.
The investigation of complement factors in lupus nephritis (LN) in relation to treatment response and the impact of underlying genetics of C4.
Seventy-seven patients with active LN confirmed by a kidney biopsy and in whom second biopsies had been performed after immunosuppressive treatment were included. Complement factors C3, C4, C4d and C4d/C4 ratio were evaluated at the biopsy time points. The gene copy number variations of C4 (C4A and C4B) were also investigated.
At baseline, 60 patients had class III/IV±V, proliferative LN (PLN) and 17 class V, membranous LN (MLN). Levels of C3 and C4 increased and C4d and C4d/C4 decreased after treatment (P < 0.0001), observed in treatment-responding PLN patients but not in MLN. C4d, C4 and C4d/C4 at second biopsies were associated with clinical response in PLN, and low C4d levels were found in PLN with histopathological response (P = 0.008). Renal activity index at second biopsies correlated to C4d and C4d/C4, but not to C3 or C4. C4 gene copy number variations were not associated with clinical or histopathological response.
All complement markers were affected by immunosuppressive therapy and associated with response to therapy. Levels of C4d and C4d/C4 at follow-up biopsies showed a strong association with both clinical and histopathological response in PLN. The correlation with elevated C4d and C4d/C4 and persisting high activity index on repeated biopsies strengthens the findings on C4d as a promising biomarker for treatment response in PLN. The C4 genetic variations did not influence C4 levels or response to treatment.
研究狼疮性肾炎（LN）中的补体因子与治疗反应的关系以及C4潜在遗传学的影响。
纳入77例经肾活检确诊为活动性LN且在免疫抑制治疗后进行了二次活检的患者。在活检时间点评估补体因子C3、C4、C4d和C4d/C4比值。还研究了C4（C4A和C4B）的基因拷贝数变异。
基线时，60例患者为III/IV±V级增殖性LN（PLN），17例为V级膜性LN（MLN）。治疗后C3和C4水平升高，C4d和C4d/C4降低（P < 0.0001），这在有治疗反应的PLN患者中观察到，但在MLN患者中未观察到。二次活检时的C4d、C4和C4d/C4与PLN的临床反应相关，在有组织病理学反应的PLN中发现C4d水平较低（P = 0.008）。二次活检时的肾脏活动指数与C4d和C4d/C4相关，但与C3或C4无关。C4基因拷贝数变异与临床或组织病理学反应无关。
所有补体标志物均受免疫抑制治疗影响并与治疗反应相关。随访活检时的C4d和C4d/C4水平与PLN的临床和组织病理学反应均密切相关。C4d和C4d/C4升高与重复活检时持续的高活动指数之间的相关性加强了C4d作为PLN治疗反应有前景的生物标志物的研究结果。C4基因变异不影响C4水平或治疗反应。
