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Apolipoprotein M Serum Levels Correlate with IgA Vasculitis and IgA Vasculitis Nephritis.

ABSTRACT: Objective:IgA vasculitis (lgAV) is the most frequent vessel vasculitis in children, and the prognosis is related to the children's age and degree of nephritis. This study is aimed at investigating serum apolipoprotein M (apoM) levels in patients with lgAV patients and at evaluating the association between apoM and disease severity. Methods:A total of 109 lgAV patients and 76 age- and sex-matched healthy controls were included. The age and gender of the study participants were matched. ApoM levels were measured by an enzyme-linked immunosorbent assay. Additionally, the serum levels of lipids, apolipoproteins, kidney biochemical profiles, immunoglobulins (IgA, IgG, IgM, and IgE), and the complements (C3 and C4) were assessed using an automatic biochemical analyzer. Results:ApoM was increased significantly in lgAV patients compared to healthy controls. ApoM, meanwhile, was lower in patients with nephritis than in those without nephritis. The apoM levels were higher in classes I and II IgA vasculitis nephritis (lgAVN) patients than in classes III and IV. Besides, the apoM serum level < 24.81?mg/L was an independent predictive factor for lgAVN and can be independently associated with the presence of nephritis in lgAV patients. Meanwhile, the serum apoM concentration negatively correlated with the ISKDC grading score in lgAVN patients. Conclusions:Serum apoM was elevated in lgAV patients and decreased gradually with the ISKDC grading score. ApoM (OR = 0.32, 95%CI = 0.12-0.85, p = 0.023) was identified as a protective factor for nephritis in all lgAV patients.

SUBMITTER: Wu J

PROVIDER: S-EPMC6927057 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Apolipoprotein M Serum Levels Correlate with IgA Vasculitis and IgA Vasculitis Nephritis.

Wu Jiali J He Lagu L Bai Le L Tan Li L Hu Min M

Disease markers 20191211

<h4>Objective</h4>IgA vasculitis (lgAV) is the most frequent vessel vasculitis in children, and the prognosis is related to the children's age and degree of nephritis. This study is aimed at investigating serum apolipoprotein M (apoM) levels in patients with lgAV patients and at evaluating the association between apoM and disease severity.<h4>Methods</h4>A total of 109 lgAV patients and 76 age- and sex-matched healthy controls were included. The age and gender of the study participants were matc ...[more]

PMID: 31885732

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Project description:BackgroundIgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAVN) are related glomerular diseases characterized by marked similarities in immunological and histological findings. We herein performed a comparative proteomic analysis of glomerular proteins in IgAN and IgAVN.MethodsWe used renal biopsy specimens from 6 IgAN patients without nephrotic syndrome (NS) (IgAN-I subgroup), 6 IgAN patients with NS (IgAN-II subgroup), 6 IgAVN patients with 0-8.0% of glomeruli with crescent formation (IgAVN-I subgroup), 6 IgAVN patients with 21.2-44.8% of glomeruli with crescent formation (IgAVN-II subgroup), 9 IgAVN patients without NS (IgAVN-III subgroup), 3 IgAVN patients with NS (IgAN-IV subgroup), and 5 control cases. Proteins were extracted from laser microdissected glomeruli and analyzed using mass spectrometry. The relative abundance of proteins was compared between groups. An immunohistochemical validation study was also performed.ResultsMore than 850 proteins with high confidence were identified. A principal component analysis revealed a clear separation between IgAN and IgAVN patients and control cases. In further analyses, 546 proteins that were matched with ≥ 2 peptides were selected. The levels of immunoglobulins (IgA, IgG, and IgM), complements (C3, C4A, C5, and C9), complement factor H-related proteins (CFHR) 1 and 5, vitronectin, fibrinogen chains, and transforming growth factor-β inducible gene-h3 were higher (> 2.6 fold) in the IgAN and IgAVN subgroups than in the control group, whereas hornerin levels were lower (< 0.3 fold). Furthermore, C9 and CFHR1 levels were significantly higher in the IgAN group than in the IgAVN group. The abundance of some podocyte-associated proteins and glomerular basement membrane (GBM) proteins was significantly less in the IgAN-II subgroup than in the IgAN-I subgroup as well as in the IgAVN-IV subgroup than in the IgAVN-III subgroup. Among the IgAN and IgAVN subgroups, talin 1 was not detected in the IgAN-II subgroup. This result was supported by immunohistochemical findings.ConclusionsThe present results suggest shared molecular mechanisms for glomerular injury in IgAN and IgAVN, except for enhanced glomerular complement activation in IgAN. Differences in the protein abundance of podocyte-associated and GBM proteins between IgAN and IgAVN patients with and without NS may be associated with the severity of proteinuria.

Project description:IntroductionPatients with IgA nephropathy (IgAN) have elevated serum levels of galactose-deficient IgA1 (Gd-IgA1) that are bound by Gd-IgA1-specific autoantibodies in pathogenic immune complexes. Renal biopsy histopathologic features of IgA vasculitis (IgAV) with nephritis (IgAV-N) are similar to those of IgAN. Mucosal infections often are associated with clinical onset and exacerbation in both diseases. We investigated whether patients with IgAV-N share pathogenic characteristics of IgAN.MethodsWe generated IgA1- and IgG-secreting cell lines from Epstein-Barr virus (EBV)-immortalized cells of patients with IgAV without nephritis (IgAV-woN), IgAV-N, and IgAN and from healthy individuals. Sera and cell-culture supernatants were used for analysis of Gd-IgA1 and Gd-IgA1-specific IgG autoantibodies.ResultsIgA1-producing cells from patients with IgAV-N, like cells from patients with IgAN, secreted more Gd-IgA1 than did cells from patients with IgAV-woN or healthy control subjects, in agreement with elevated serum Gd-IgA1 levels in patients with IgAV-N and IgAN. IgA1-producing cells from patients with IgAV-N had altered expression of genes involved in O-glycan biosynthesis: decreased for core 1 synthase (glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1; C1GALT1) and C1GALT1 Specific Chaperone 1 (C1GALTC1; COSMC) and elevated for N-acetylgalactosaminide α-2,6-sialyltransferase 2 (ST6GALNAC2). Levels of Gd-IgA1-specific IgG in sera and supernatants of IgG-producing cells were similar for patients with IgAV-N and IgAN and higher than those for IgAV-woN patients or healthy control subjects. Moreover, patients with IgAV-N who had active disease, manifested by hematuria and substantial proteinuria, had higher serum levels of Gd-IgA1-specific IgG autoantibodies than did patients with IgAV-N who had inactive disease.ConclusionSerum levels and cellular production of Gd-IgA1 and Gd-IgA1-specific IgG autoantibodies were elevated in patients with IgAV-N, supporting the hypothesis that IgAV-N and IgAN share pathogenic features.

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Apolipoprotein M Serum Levels Correlate with IgA Vasculitis and IgA Vasculitis Nephritis.

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Apolipoprotein M Serum Levels Correlate with IgA Vasculitis and IgA Vasculitis Nephritis.

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