The anti-mCRP199-206 antibodies aggravate tubulointerstitial lesions in lupus nephritis

被引：2
作者：
Yuan, Mo [1 ,2 ,3 ,4 ,5 ,6 ,7 ]
Zhao, Ming-hui [1 ,2 ,3 ,4 ,5 ]
Tan, Ying [1 ,2 ,3 ,4 ,5 ]
机构：
[1] Peking Univ First Hosp, Dept Med, Renal Div, 8 Xishiku St, Beijing 100034, Peoples R China
[2] Peking Univ, Inst Nephrol, Beijing, Peoples R China
[3] Minist Hlth China, Key Lab Renal Dis, Beijing, Peoples R China
[4] Minist Educ China, Key Lab Chron Kidney Dis Prevent & Treatment, Beijing, Peoples R China
[5] Chinese Acad Med Sci, Res Units Diag & Treatment Immune Mediated Kidney, Beijing, Peoples R China
[6] Yunnan Univ, Sch Med, Kunming, Peoples R China
[7] Yunnan Univ, Affiliated Hosp, Peoples Hosp Yunnan Prov 2, Dept Pathol, Kunming, Peoples R China
来源：
CLINICAL IMMUNOLOGY | 2024年 / 268卷
基金：
中国国家自然科学基金; 北京市自然科学基金;
关键词：
Systemic lupus erythematosus; Lupus nephritis; Tubulointerstitial lesions; Anti-modified /monomeric C-reactive protein; antibody; C-reactive protein; C-REACTIVE PROTEIN; DISEASE-ACTIVITY; INTERNATIONAL SOCIETY; RENAL OUTCOMES; AUTOANTIBODIES; INFLAMMATION; IDENTIFICATION; ACTIVATION; CLASSIFICATION; TGF-BETA-1;
D O I：
10.1016/j.clim.2024.110353
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Tubulointerstitial lesions could also be prominent in lupus nephritis, and the pathogenesis of tubulointerstitial lesions may be different from glomerular lesions. Previous studies have showed that plasma antibodies against modified/monomeric C-reactive protein (mCRP) are associated with renal tubulointerstitial lesions in patients with lupus nephritis, and amino acid (aa) 199-206 was one of the major epitopes of mCRP. However, the role of anti-mCRP(199-206) antibodies in the pathogenesis of tubulointerstitial lesions in lupus nephritis is unknown. A total of 95 patients with renal biopsy-proven lupus nephritis were enrolled in this study. Plasma levels of antimCRP(199-206) antibodies were screened by enzyme-linked immunosorbent assay (ELISA). A lupus prone mouse model was immunized using peptides mCRP(199-206) to explore the potential role of anti-mCRP(199-206) antibodies in tubulointerstitial lesions. The mechanism of anti-mCRP(199-206) antibodies damage to renal tubular epithelial cells was investigated in vitro. Plasma antibodies against mCRP(199-206) were associated with renal tubulointerstitial lesions and prognosis in patients with lupus nephritis. Immunization with peptides mCRP(199-206) in lupus prone mice could aggravate tubulointerstitial lesions and drive tubulointerstitial inflammation and fibrosis. Anti-mCRP(199-206) antibodies could activate the TGF-beta 1/Smad3 signal pathway and induce tubular damage by binding with CRP. Circulating antibodies against mCRP(199-206) could be a biomarker to reveal tubulointerstitial lesion, and participate in the pathogenesis of tubulointerstitial lesions, which might provide a potential therapeutic target for lupus nephritis.
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页数：12
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