Complement Activation Is Associated With Crescents in IgA Nephropathy
IntroductionCrescents, especially those found at a percentage greater than 50%, are often associated with rapid progression of kidney disease in IgA nephropathy (IgAN). The mechanism of crescents forming in IgAN is still unclear. In this study, we aimed to evaluate whether excess complement activati...
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Frontiers Media S.A.
2021-09-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.676919/full |
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| author | Zi Wang Zi Wang Zi Wang Xinfang Xie Xinfang Xie Xinfang Xie Jingyi Li Jingyi Li Jingyi Li Xue Zhang Xue Zhang Xue Zhang Jiawei He Jiawei He Jiawei He Manliu Wang Manliu Wang Manliu Wang Jicheng Lv Jicheng Lv Jicheng Lv Hong Zhang Hong Zhang Hong Zhang |
| author_facet | Zi Wang Zi Wang Zi Wang Xinfang Xie Xinfang Xie Xinfang Xie Jingyi Li Jingyi Li Jingyi Li Xue Zhang Xue Zhang Xue Zhang Jiawei He Jiawei He Jiawei He Manliu Wang Manliu Wang Manliu Wang Jicheng Lv Jicheng Lv Jicheng Lv Hong Zhang Hong Zhang Hong Zhang |
| author_sort | Zi Wang |
| collection | DOAJ |
| description | IntroductionCrescents, especially those found at a percentage greater than 50%, are often associated with rapid progression of kidney disease in IgA nephropathy (IgAN). The mechanism of crescents forming in IgAN is still unclear. In this study, we aimed to evaluate whether excess complement activation participates in the formation of crescents in IgAN.MethodsOne hundred IgAN patients with various proportions of crescents—24 with 1%–24%, 27 with 25%–49%, 21 with 50%–74% 12 with more than 75%, and 16 without crescents—were included. Urinary concentrations of mannose-binding lectin (MBL), Bb, C4d, C3a, C5a, and soluble C5b-9 (sC5b-9) were measured at the time of biopsy. Receiver operating characteristic (ROC) curves were performed to evaluate predictive ability of renal survival for urine complement activation. In addition, historical C4d, C5b-9, and C3d were stained by immunohistochemistry.ResultsIgAN patients with more than 50% crescent formation showed higher complement activation levels than the other patients (urinary C3a/creatinine (C3a/Cr): 6.7295 ng/mg, interquartile range (IQR) 1.4652–62.1086 ng/mg vs. 0.1055 ng/mg, IQR 0–1.4089 ng/mg; urinary C5a/Cr: 15.6202 ng/mg, 4.3127–66.7347 ng/mg vs. 0.3280 ng/mg, IQR 0.0859–2.4439 ng/mg; urinary sC5b-9/Cr: 98.6357 ng/mg, 8.8058–1,087.4578 ng/mg vs. 1.4262 ng/mg, 0.0916–11.0858 ng/mg, all p-values <0.001). The levels of urinary MBL and C4d representing lectin complement pathway showed a linear association with the proportion of crescents (r = 0.457 and 0.562, respectively, both p-values <0.001). Combined urine complement products could increase the predictive ability compared with crescents alone from 0.904 to 0.944 (p = 0.062) with borderline significance. Moreover, the glomerular C4d deposition rate elevated with the increase of proportions of crescents.ConclusionExcess complement activation may be involved in the formation of crescents, especially diffuse crescent formation, in patients with IgAN. Urinary C4d correlated with the proportion of crescents and was a potential biomarker for disease monitoring in crescentic IgAN. |
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| publishDate | 2021-09-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-95dd2d7afb0140a68ac30edf3bba0e942022-12-21T18:32:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.676919676919Complement Activation Is Associated With Crescents in IgA NephropathyZi Wang0Zi Wang1Zi Wang2Xinfang Xie3Xinfang Xie4Xinfang Xie5Jingyi Li6Jingyi Li7Jingyi Li8Xue Zhang9Xue Zhang10Xue Zhang11Jiawei He12Jiawei He13Jiawei He14Manliu Wang15Manliu Wang16Manliu Wang17Jicheng Lv18Jicheng Lv19Jicheng Lv20Hong Zhang21Hong Zhang22Hong Zhang23Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaResearch Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, ChinaRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaResearch Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, ChinaRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaResearch Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, ChinaRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaResearch Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, ChinaRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaResearch Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, ChinaRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaResearch Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, ChinaRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaResearch Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, ChinaRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, ChinaResearch Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, ChinaIntroductionCrescents, especially those found at a percentage greater than 50%, are often associated with rapid progression of kidney disease in IgA nephropathy (IgAN). The mechanism of crescents forming in IgAN is still unclear. In this study, we aimed to evaluate whether excess complement activation participates in the formation of crescents in IgAN.MethodsOne hundred IgAN patients with various proportions of crescents—24 with 1%–24%, 27 with 25%–49%, 21 with 50%–74% 12 with more than 75%, and 16 without crescents—were included. Urinary concentrations of mannose-binding lectin (MBL), Bb, C4d, C3a, C5a, and soluble C5b-9 (sC5b-9) were measured at the time of biopsy. Receiver operating characteristic (ROC) curves were performed to evaluate predictive ability of renal survival for urine complement activation. In addition, historical C4d, C5b-9, and C3d were stained by immunohistochemistry.ResultsIgAN patients with more than 50% crescent formation showed higher complement activation levels than the other patients (urinary C3a/creatinine (C3a/Cr): 6.7295 ng/mg, interquartile range (IQR) 1.4652–62.1086 ng/mg vs. 0.1055 ng/mg, IQR 0–1.4089 ng/mg; urinary C5a/Cr: 15.6202 ng/mg, 4.3127–66.7347 ng/mg vs. 0.3280 ng/mg, IQR 0.0859–2.4439 ng/mg; urinary sC5b-9/Cr: 98.6357 ng/mg, 8.8058–1,087.4578 ng/mg vs. 1.4262 ng/mg, 0.0916–11.0858 ng/mg, all p-values <0.001). The levels of urinary MBL and C4d representing lectin complement pathway showed a linear association with the proportion of crescents (r = 0.457 and 0.562, respectively, both p-values <0.001). Combined urine complement products could increase the predictive ability compared with crescents alone from 0.904 to 0.944 (p = 0.062) with borderline significance. Moreover, the glomerular C4d deposition rate elevated with the increase of proportions of crescents.ConclusionExcess complement activation may be involved in the formation of crescents, especially diffuse crescent formation, in patients with IgAN. Urinary C4d correlated with the proportion of crescents and was a potential biomarker for disease monitoring in crescentic IgAN.https://www.frontiersin.org/articles/10.3389/fimmu.2021.676919/fullimmunoglobulin A nephropathy (IgAN)crescentcomplementlectin pathwayurinary C4d |
| spellingShingle | Zi Wang Zi Wang Zi Wang Xinfang Xie Xinfang Xie Xinfang Xie Jingyi Li Jingyi Li Jingyi Li Xue Zhang Xue Zhang Xue Zhang Jiawei He Jiawei He Jiawei He Manliu Wang Manliu Wang Manliu Wang Jicheng Lv Jicheng Lv Jicheng Lv Hong Zhang Hong Zhang Hong Zhang Complement Activation Is Associated With Crescents in IgA Nephropathy Frontiers in Immunology immunoglobulin A nephropathy (IgAN) crescent complement lectin pathway urinary C4d |
| title | Complement Activation Is Associated With Crescents in IgA Nephropathy |
| title_full | Complement Activation Is Associated With Crescents in IgA Nephropathy |
| title_fullStr | Complement Activation Is Associated With Crescents in IgA Nephropathy |
| title_full_unstemmed | Complement Activation Is Associated With Crescents in IgA Nephropathy |
| title_short | Complement Activation Is Associated With Crescents in IgA Nephropathy |
| title_sort | complement activation is associated with crescents in iga nephropathy |
| topic | immunoglobulin A nephropathy (IgAN) crescent complement lectin pathway urinary C4d |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.676919/full |
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