Combination of anti-C1qA08 and anti-mCRP a.a.35-47 antibodies is associated with renal prognosis of patients with lupus nephritis

ObjectiveThe aim of this study is to explore the prevalence and clinicopathological associations between anti-C1qA08 antibodies and anti-monomeric CRP (mCRP) a.a.35-47 antibodies and to explore the interaction between C1q and mCRP.MethodsNinety patients with biopsy-proven lupus nephritis were includ...

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Main Authors: Xiao-Ling Liu, Ying Tan, Feng Yu, Shang-Rong Ji, Ming-Hui Zhao
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1181561/full
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author Xiao-Ling Liu
Xiao-Ling Liu
Xiao-Ling Liu
Xiao-Ling Liu
Xiao-Ling Liu
Xiao-Ling Liu
Ying Tan
Ying Tan
Ying Tan
Ying Tan
Ying Tan
Feng Yu
Shang-Rong Ji
Ming-Hui Zhao
Ming-Hui Zhao
Ming-Hui Zhao
Ming-Hui Zhao
Ming-Hui Zhao
author_facet Xiao-Ling Liu
Xiao-Ling Liu
Xiao-Ling Liu
Xiao-Ling Liu
Xiao-Ling Liu
Xiao-Ling Liu
Ying Tan
Ying Tan
Ying Tan
Ying Tan
Ying Tan
Feng Yu
Shang-Rong Ji
Ming-Hui Zhao
Ming-Hui Zhao
Ming-Hui Zhao
Ming-Hui Zhao
Ming-Hui Zhao
author_sort Xiao-Ling Liu
collection DOAJ
description ObjectiveThe aim of this study is to explore the prevalence and clinicopathological associations between anti-C1qA08 antibodies and anti-monomeric CRP (mCRP) a.a.35-47 antibodies and to explore the interaction between C1q and mCRP.MethodsNinety patients with biopsy-proven lupus nephritis were included from a Chinese cohort. Plasma samples collected on the day of renal biopsy were tested for anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies. The associations between these two autoantibodies and clinicopathologic features and long-term prognosis were analyzed. The interaction between C1q and mCRP was further investigated by ELISA, and the key linear epitopes of the combination of cholesterol binding sequence (CBS; a.a.35-47) and C1qA08 were tested by competitive inhibition assays. The surface plasmon resonance (SPR) was used to further verify the results.ResultsThe prevalence of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were 50/90 (61.1%) and 45/90 (50.0%), respectively. Levels of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were negatively correlated with serum C3 concentrations ((0.5(0.22-1.19) g/L vs. 0.39(0.15-1.38) g/L, P=0.002) and (0.48(0.44-0.88) g/L vs. 0.41(0.15-1.38) g/L, P=0.028), respectively. Levels of anti-C1qA08 antibodies were correlated with the score of fibrous crescents and tubular atrophy (r=-0.256, P=0.014 and r=-0.25, P=0.016, respectively). The patients with double positive antibodies showed worse renal prognosis than that of the double negative group (HR 0.899 (95% CI: 0.739-1.059), P=0.0336). The binding of mCRP to C1q was confirmed by ELISA. The key linear epitopes of the combination were a.a.35-47 and C1qA08, which were confirmed by competitive inhibition experiments and SPR.ConclusionThe combination of anti-C1qA08 and anti-mCRP a.a.35-47 autoantibodies could predict a poor renal outcome. The key linear epitopes of the combination of C1q and mCRP were C1qA08 and a.a.35-47. A08 was an important epitope for the classical pathway complement activation and a.a.35-47 could inhibit this process.
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spelling doaj.art-b033fb0d9479411297c5554da01fe9db2023-04-17T05:41:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11815611181561Combination of anti-C1qA08 and anti-mCRP a.a.35-47 antibodies is associated with renal prognosis of patients with lupus nephritisXiao-Ling Liu0Xiao-Ling Liu1Xiao-Ling Liu2Xiao-Ling Liu3Xiao-Ling Liu4Xiao-Ling Liu5Ying Tan6Ying Tan7Ying Tan8Ying Tan9Ying Tan10Feng Yu11Shang-Rong Ji12Ming-Hui Zhao13Ming-Hui Zhao14Ming-Hui Zhao15Ming-Hui Zhao16Ming-Hui Zhao17Ministry of Education (MOE) Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, ChinaRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease (CKD) Prevention and Treatment, Ministry of Education of China, Beijing, ChinaResearch Units of Diagnosis and Treatment of lmmune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, ChinaRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease (CKD) Prevention and Treatment, Ministry of Education of China, Beijing, ChinaResearch Units of Diagnosis and Treatment of lmmune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Nephrology, Peking University International Hospital, Beijing, ChinaMinistry of Education (MOE) Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, ChinaRenal Division, Peking University First Hospital, Beijing, ChinaInstitute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease (CKD) Prevention and Treatment, Ministry of Education of China, Beijing, ChinaResearch Units of Diagnosis and Treatment of lmmune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, ChinaObjectiveThe aim of this study is to explore the prevalence and clinicopathological associations between anti-C1qA08 antibodies and anti-monomeric CRP (mCRP) a.a.35-47 antibodies and to explore the interaction between C1q and mCRP.MethodsNinety patients with biopsy-proven lupus nephritis were included from a Chinese cohort. Plasma samples collected on the day of renal biopsy were tested for anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies. The associations between these two autoantibodies and clinicopathologic features and long-term prognosis were analyzed. The interaction between C1q and mCRP was further investigated by ELISA, and the key linear epitopes of the combination of cholesterol binding sequence (CBS; a.a.35-47) and C1qA08 were tested by competitive inhibition assays. The surface plasmon resonance (SPR) was used to further verify the results.ResultsThe prevalence of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were 50/90 (61.1%) and 45/90 (50.0%), respectively. Levels of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were negatively correlated with serum C3 concentrations ((0.5(0.22-1.19) g/L vs. 0.39(0.15-1.38) g/L, P=0.002) and (0.48(0.44-0.88) g/L vs. 0.41(0.15-1.38) g/L, P=0.028), respectively. Levels of anti-C1qA08 antibodies were correlated with the score of fibrous crescents and tubular atrophy (r=-0.256, P=0.014 and r=-0.25, P=0.016, respectively). The patients with double positive antibodies showed worse renal prognosis than that of the double negative group (HR 0.899 (95% CI: 0.739-1.059), P=0.0336). The binding of mCRP to C1q was confirmed by ELISA. The key linear epitopes of the combination were a.a.35-47 and C1qA08, which were confirmed by competitive inhibition experiments and SPR.ConclusionThe combination of anti-C1qA08 and anti-mCRP a.a.35-47 autoantibodies could predict a poor renal outcome. The key linear epitopes of the combination of C1q and mCRP were C1qA08 and a.a.35-47. A08 was an important epitope for the classical pathway complement activation and a.a.35-47 could inhibit this process.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1181561/fullanti-C1qA08 autoantibodyanti-mCRP a.a.35-47 autoantibodyautoantibodiesrenal prognosislupus nephritis
spellingShingle Xiao-Ling Liu
Xiao-Ling Liu
Xiao-Ling Liu
Xiao-Ling Liu
Xiao-Ling Liu
Xiao-Ling Liu
Ying Tan
Ying Tan
Ying Tan
Ying Tan
Ying Tan
Feng Yu
Shang-Rong Ji
Ming-Hui Zhao
Ming-Hui Zhao
Ming-Hui Zhao
Ming-Hui Zhao
Ming-Hui Zhao
Combination of anti-C1qA08 and anti-mCRP a.a.35-47 antibodies is associated with renal prognosis of patients with lupus nephritis
Frontiers in Immunology
anti-C1qA08 autoantibody
anti-mCRP a.a.35-47 autoantibody
autoantibodies
renal prognosis
lupus nephritis
title Combination of anti-C1qA08 and anti-mCRP a.a.35-47 antibodies is associated with renal prognosis of patients with lupus nephritis
title_full Combination of anti-C1qA08 and anti-mCRP a.a.35-47 antibodies is associated with renal prognosis of patients with lupus nephritis
title_fullStr Combination of anti-C1qA08 and anti-mCRP a.a.35-47 antibodies is associated with renal prognosis of patients with lupus nephritis
title_full_unstemmed Combination of anti-C1qA08 and anti-mCRP a.a.35-47 antibodies is associated with renal prognosis of patients with lupus nephritis
title_short Combination of anti-C1qA08 and anti-mCRP a.a.35-47 antibodies is associated with renal prognosis of patients with lupus nephritis
title_sort combination of anti c1qa08 and anti mcrp a a 35 47 antibodies is associated with renal prognosis of patients with lupus nephritis
topic anti-C1qA08 autoantibody
anti-mCRP a.a.35-47 autoantibody
autoantibodies
renal prognosis
lupus nephritis
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1181561/full
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