Di Song1, Wei-Yi Guo1, Feng-Mei Wang1, Yong-Zhe Li2, Yan Song3, Feng Yu4, Ming-Hui Zhao5. 1. Department of Medicine, Peking University First Hospital, Beijing, China; Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing, China. 2. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education of China, Beijing, China. 3. Department of Nephrology, the First Affiliated Hospital of Chinese PLA General Hospital, Beijing, P.R. China. Electronic address: songyan0209@163.com. 4. Department of Medicine, Peking University First Hospital, Beijing, China; Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing, China; Department of Nephrology, Peking University International Hospital, Beijing, P.R. China. 5. Department of Medicine, Peking University First Hospital, Beijing, China; Peking University Institute of Nephrology, Beijing, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing, China; Peking-Tsinghua Center for Life Sciences, Beijing, P.R. China.
Abstract
OBJECTIVE: The aim of this study was to detect the spectrum of complement activation pathways in circulation and to assess their correlations with clinical and pathologic features in a large lupus nephritis cohort from China. MATERIALS AND METHODS: Plasma levels of C1q, mannose-binding lectin, C4d, Bb, C3, C3a, C5a and soluble C5b-9 were detected by enzyme-linked immunosorbent assay in 222 patients with active biopsy-proven lupus nephritis, 34 patients with lupus nephritis at remission, 82 patients with active systemic lupus erythematosus without renal involvement and 39 normal controls. The correlations between levels of complement components and clinicopathological features of these patients were further analyzed. RESULTS: Plasma levels of C1q and C3 significantly decreased, and the levels of Bb, C3a, C5a and soluble C5b-9 were significantly elevated in patients with active lupus nephritis compared with those in remission, active systemic lupus erythematosus without renal involvement group and normal controls. In the lupus nephritis group, soluble C5b-9 levels were inversely correlated with C1q and C4d levels (r = -0.412, P < 0.001 and r = -0.221, P = 0.002, respectively), but more strongly correlated with the level of Bb (r = 0.546, P < 0.001). C3b, Bb and C5b-9 could colocalize on glomeruli in lupus nephritis. Plasma Bb level was significantly correlated with some renal disease activity indices and was a risk factor for renal outcomes (hazard ratio = 1.745; 95% CI: 1.106-2.754; P = 0.017) in the lupus nephritis group. CONCLUSIONS: Our findings suggested that the activation of the complement alternative pathway might play a more important role in the pathogenesis of lupus nephritis, and factor Bb might be a useful marker for evaluating renal disease activity and outcomes.
OBJECTIVE: The aim of this study was to detect the spectrum of complement activation pathways in circulation and to assess their correlations with clinical and pathologic features in a large lupus nephritis cohort from China. MATERIALS AND METHODS: Plasma levels of C1q, mannose-binding lectin, C4d, Bb, C3, C3a, C5a and soluble C5b-9 were detected by enzyme-linked immunosorbent assay in 222 patients with active biopsy-proven lupus nephritis, 34 patients with lupus nephritis at remission, 82 patients with active systemic lupus erythematosus without renal involvement and 39 normal controls. The correlations between levels of complement components and clinicopathological features of these patients were further analyzed. RESULTS: Plasma levels of C1q and C3 significantly decreased, and the levels of Bb, C3a, C5a and soluble C5b-9 were significantly elevated in patients with active lupus nephritis compared with those in remission, active systemic lupus erythematosus without renal involvement group and normal controls. In the lupus nephritis group, soluble C5b-9 levels were inversely correlated with C1q and C4d levels (r = -0.412, P < 0.001 and r = -0.221, P = 0.002, respectively), but more strongly correlated with the level of Bb (r = 0.546, P < 0.001). C3b, Bb and C5b-9 could colocalize on glomeruli in lupus nephritis. Plasma Bb level was significantly correlated with some renal disease activity indices and was a risk factor for renal outcomes (hazard ratio = 1.745; 95% CI: 1.106-2.754; P = 0.017) in the lupus nephritis group. CONCLUSIONS: Our findings suggested that the activation of the complement alternative pathway might play a more important role in the pathogenesis of lupus nephritis, and factor Bb might be a useful marker for evaluating renal disease activity and outcomes.
Authors: Juan M Mejia-Vilet; Ismael A Gómez-Ruiz; Cristino Cruz; R Angélica Méndez-Pérez; Roque A Comunidad-Bonilla; Norma O Uribe-Uribe; Carlos A Nuñez-Alvarez; Luis E Morales-Buenrostro Journal: Clin Rheumatol Date: 2020-11-10 Impact factor: 2.980