Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Department of Clinical Immunology and Rheumatology, AIIMS, New Delhi, India.
Lupus. 2020 Nov;29(13):1800-1806. doi: 10.1177/0961203320950019. Epub 2020 Aug 17.
Complement activation is central to the pathogenesis of lupus nephritis (LN). Low serum complement C3 and C4, are traditionally used as markers of lupus disease activity in general and LN in particular. In this study we prospectively measured plasma and urine C3d and C4d, degradation products of C3 and C4 corrected to creatinine in a cohort of biopsy proven LN in a longitudinal fashion for its correlation with disease activity.
Twenty eight biopsy proven active lupus nephritis (AN) were recruited along with four inactive nephritis (IN) and 10 healthy controls (HC). Plasma and urine were collected at baseline, prior to induction treatment and 3 months later. Clinical measures of disease activity, Systemic lupus erythematosus disease activity index 2000 (SLEDAI 2K), renal SLEDAI, serum C3, C4 and antibodies to ds DNA, urine protein and creatinine excretion (UP/UC) were collected. Plasma and urine C3d and C4d were measured using ELISA and normalized to spot urine creatinine value.
Twenty eight AN of median age of 26.5 (20-31.50) years and disease duration of 3 (0.7-5) years were enrolled. The median urinary C3d/creatinine before treatment was 388.20 (48.98-1296) ng/mg which fell significantly to 62.69 (28.04-502.4) ng/mg at 3 months followup (p-0.01). The baseline values for the active renal disease was significantly different from IN group (9.9 (4.5-46.53 ng/mg) p-0.00). Treatment responders (partial and complete) at 6 months showed a significant fall in urinary C3d at 3 months whereas non responders had a non significant change in value. There was a significant correlation of urine C3d/creatinine with SLEDAI2K (r-0.433, p-0.00), renal SLEDAI (r-0.356, p-0.00), UP/UC ratio (r-0.489, p-<0.0001) but no significant correlation with C3 or C4. There was a significant fall in the median values of plasma C3d from 791.1 (516.0.00-1550.43) µg/ml to 338.52 (211.35-525.82) (p-0.00) µg/ml at the end of 3 months. The values showed a significant correlation with SLEDAI 2K, renal SLEDAI, UP/UC along with a significant negative correlation with C3 and C4.
Urinary C3d/creatinine levels and plasma C3d levels can be used as biomarker of disease activity and treatment response.
补体激活是狼疮肾炎（LN）发病机制的核心。血清补体 C3 和 C4 水平降低通常被用作狼疮疾病活动度的标志物，尤其是 LN。在这项研究中，我们前瞻性地测量了血浆和尿液中的 C3d 和 C4d，这是 C3 和 C4 的降解产物，并用肌酐进行了校正，并对经活检证实的 LN 患者进行了纵向研究，以确定其与疾病活动度的相关性。
共招募了 28 例活检证实的活动性狼疮肾炎（AN）患者，4 例非活动性肾炎（IN）患者和 10 例健康对照者（HC）。在诱导治疗前、基线和 3 个月后收集血浆和尿液。收集临床疾病活动度指标，系统性红斑狼疮疾病活动指数 2000（SLEDAI 2K）、肾脏 SLEDAI、血清 C3、C4 和抗 dsDNA 抗体、尿蛋白和肌酐排泄率（UP/UC）。使用 ELISA 测量血浆和尿液中的 C3d 和 C4d，并将其标准化为尿液肌酐值。
共纳入 28 例年龄中位数为 26.5（20-31.50）岁，病程 3（0.7-5）年的 AN 患者。治疗前尿液 C3d/肌酐中位数为 388.20（48.98-1296）ng/mg，治疗后 3 个月显著下降至 62.69（28.04-502.4）ng/mg（p-0.01）。活动期肾脏疾病的基线值与 IN 组有显著差异（9.9（4.5-46.53 ng/mg），p-0.00）。6 个月时治疗反应者（部分和完全）在 3 个月时尿液 C3d 显著下降，而非反应者 C3d 值无显著变化。尿液 C3d/肌酐与 SLEDAI2K（r-0.433，p-0.00）、肾脏 SLEDAI（r-0.356，p-0.00）、UP/UC 比值（r-0.489，p-<0.0001）呈显著相关性，但与 C3 或 C4 无显著相关性。血浆 C3d 的中位数从 791.1（516.00-1550.43）µg/ml 显著下降至 338.52（211.35-525.82）µg/ml（p-0.00）µg/ml，在 3 个月结束时。这些值与 SLEDAI 2K、肾脏 SLEDAI、UP/UC 呈显著相关性，与 C3 和 C4 呈显著负相关。
尿液 C3d/肌酐水平和血浆 C3d 水平可作为疾病活动度和治疗反应的生物标志物。
