المؤلفون: Yue-miao Zhang, Xing-zi Liu, Xu-jie Zhou, Li-jun Liu, Su-fang Shi, Ping Hou, Ji-cheng Lv, Hong Zhang

المصدر: Frontiers in Immunology, Vol 12 (2021)
Frontiers in Immunology

مصطلحات موضوعية: Adult, Male, Receptors, CCR6, lcsh:Immunologic diseases. Allergy, 0301 basic medicine, China, Linkage disequilibrium, Genotype, genetic association, Quantitative Trait Loci, Immunology, Gene Expression, C-C chemokine receptor type 6, Biology, Kidney Function Tests, CXCR3, Polymorphism, Single Nucleotide, Young Adult, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Meta-Analysis as Topic, Polymorphism (computer science), Humans, Immunology and Allergy, Genetic Predisposition to Disease, Th17 cells, Allele, Alleles, Original Research, Genetic association, Computational Biology, Glomerulonephritis, IGA, Molecular Sequence Annotation, IgA nephropathy, Middle Aged, functional annotation, Molecular biology, Phenotype, 030104 developmental biology, Case-Control Studies, Expression quantitative trait loci, Female, CCR6, lcsh:RC581-607, CD8

الوصف: C-C chemokine receptor 6 (CCR6) is a susceptibility gene of various immune-related diseases, which was suggested to be shared with immunoglobulin A nephropathy (IgAN). In this study, we aimed to identify the functional variants. First, we analyzed the associations ofCCR6common and rare variants detected by multi-platform chips with IgAN susceptibility using imputation and identified 68 significantly associated common variants located in the regulatory region. Among them, rs3093023 showed both statistical significance (rs3093023-A, odds ratio [OR] = 1.15,P= 2.00 × 10−2) and the expression quantitative trait loci (eQTL) effect (P= 1.45 × 10−3). It was independently replicated (rs3093023-A, OR = 1.18,P= 5.56 × 10−3) and the association was reinforced in the meta-analysis (rs3093023-A, OR = 1.17,P= 6.14 × 10−7). Although rs3093023 was in a strong linkage disequilibrium with the reportedCCR6functional variant dinucleotide polymorphism,CCR6DNP, the alleles of rs3093023 (G>A) rather than ofCCR6DNPwere shown differential nuclear protein binding effect by electrophoretic mobility shift assay. The RegulomeDB and JASPAR databases predicted Pou2f1 as the potential transcription factor, which was negatively associated withCCR6mRNA (r= −0.60,P= 3.94 × 10−9). At the mRNA level, the eQTL effect ofCCR6was validated (P= 4.39 × 10−2), andCCR6was positively associated with the expression ofCCR4andIL-17Arather than that ofCXCR3andIFNG. At the protein level, a higher CCR6+cell ratio was observed in a risk allele dose-dependent manner in lymphocytes (P= 3.57 × 10−2), CD3+T cells (P= 4.54 × 10−2), and CD4+T cells (P= 1.32 × 10−2), but not in CD8+T cells. Clinical-pathological analysis showed that rs3093023 risk allele was significantly associated with diastolic blood pressure, serum creatinine, and high ratio of tubular atrophy/interstitial fibrosis. Overall, the rs3093023 was prioritized as the function variant inCCR6, which may contribute to IgAN susceptibility by regulating Th17 cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c25497e4fedda7fcaad3ba58eab7a6dTest
https://doi.org/10.3389/fimmu.2021.600598Test

المؤلفون: Guizhen Yu, Jicheng Lv, Manliu Wang, Zewei Ying, Wenke Han, Xin Xu, Zi Wang, Hong Zhang, Xu-jie Zhou, Xue Zhang

المصدر: International Immunopharmacology. 91:107282

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Immunoglobulin A, medicine.drug_class, Immunology, chemical and pharmacologic phenomena, Immunofluorescence, Monoclonal antibody, Nephropathy, 03 medical and health sciences, fluids and secretions, 0302 clinical medicine, Immune system, stomatognathic system, Polysaccharides, Living Donors, Prevalence, medicine, Humans, Immunology and Allergy, Autoantibodies, Subclinical infection, Pharmacology, Kidney, medicine.diagnostic_test, biology, business.industry, Glomerulonephritis, IGA, Middle Aged, medicine.disease, Kidney Transplantation, Glomerular Mesangium, 030104 developmental biology, medicine.anatomical_structure, Beijing, Case-Control Studies, 030220 oncology & carcinogenesis, biology.protein, Female, Antibody, business

الوصف: Background There are few studies describing the prevalence and immune features of people with subclinical mesangial immunoglobulin A (IgA) deposition in the Chinese population. We sought to investigate the prevalence of mesangial IgA deposition among kidney donors and the immune characteristics of donors with mesangial IgA deposition. Methods Fifty blood-related living donors with zero-hour allograft biopsies obtained at Peking University First Hospital were enrolled. Galactose-deficient IgA1 (Gd-IgA1) in glomerular deposits was examined by double immunofluorescent staining using the specific monoclonal antibody KM55. Plasma IgA, IgA1, Gd-IgA1 and antibodies directed against Gd-IgA1 were measured using enzyme-linked immunosorbent assay. Results Thirteen of 50 (26%) donors had mesangial IgA deposition, which was confirmed by both immunofluorescence and electron microscopy. The levels of plasma IgA, IgA1 and Gd-IgA1 were all increased in donors with IgA deposition compared with those without IgA deposition (mean ± SD, 3.54 ± 0.505 versus 2.356 ± 0.265 mg/ml, p = 0.049; 3.003 ± 0.4048 versus 2.356 ± 0.265 mg/ml, p = 0.057; and 4.719 ± 0.4357 versus 3.356 ± 0.4707 ug/ml, p = 0.0440, respectively). Colocalized IgA1 and Gd-IgA1 indicated that there were galactose-deficient IgA1 deposits in the glomerular mesangium. While donors with IgA deposition showed lower levels of IgG anti-glycan antibodies than patients with IgA nephropathy (37.71 ± 8.886 versus 78.86 ± 5.155 units/ml, p = 0.001). Conclusions The immune features of donors with IgA deposition, including IgA1 and Gd-IgA1 deposition, were similar to those of patients with IgA nephropathy, but donors with IgA deposition had lower levels of antiglycan antibodies, which may explain the subclinical status of IgA deposition in donors. Mesangial IgA deposition was common in the Chinese blood related donors cohort, further large study with both living and cadaveric donor kidneys was still needed to confirm these findings.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ead24b94afa615e3a9868b81e0a3b36cTest
https://doi.org/10.1016/j.intimp.2020.107282Test

المؤلفون: Jian-qun Su, Chen Wang, Suxia Wang, Li Yang, Xiaojuan Yu, Tao Su, Gang Liu, Pingping Sun, Jing Nie, Xu-jie Zhou

المصدر: Clinical immunology (Orlando, Fla.). 205

مصطلحات موضوعية: 0301 basic medicine, Adult, Male, Pathology, medicine.medical_specialty, Glomerulonephritis, Membranoproliferative, Urinary system, Immunology, Macrophage polarization, Cell Count, Urine, urologic and male genital diseases, Kidney, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Glomerulonephritis, Glomerulopathy, medicine, Immunology and Allergy, Humans, Acute tubulointerstitial nephritis, medicine.diagnostic_test, urogenital system, business.industry, Thrombotic Microangiopathies, Macrophages, Acute kidney injury, Acute Kidney Injury, Kidney Tubular Necrosis, Acute, Middle Aged, medicine.disease, female genital diseases and pregnancy complications, 030104 developmental biology, medicine.anatomical_structure, Nephritis, Interstitial, Female, Renal biopsy, business, 030215 immunology

الوصف: Macrophage polarization is a major contributing factor in acute kidney injury (AKI). We aim to determine its biomarker value in differentiating etiologic causes of various intrinsic renal AKI. A total of 205 patients with renal intrinsic AKI were enrolled. Urinary sCD163 was quantified and macrophage subtypes in urine and in renal biopsy were determined. Compared to healthy controls and AKI due to interstitial or tubular injuries (0 pg/μmol), urinary sCD163 was markedly higher in glomerulopathy, especially in diffuse proliferative glomerulonephritis (275.5 pg/μmol) and significantly correlated with cellular crescent formation. Urine sediment analysis of M1/M2 ratio could differentiate acute tubulointerstitial nephritis (M1/M2 2.35) from crescentic glomerulonephritis (M1/M2 0.27). Urinary sCD163 levels and M2 subtype positively correlated with infiltrated M2 in the glomeruli, whereas urine M1 positively correlated with infiltrated M1 in the interstitium. Of note, urinary sCD163 showed better diagnositic performance in differentiating disease etiologies compared to tradiational urinary biomarkers of AKI (NGAL and KIM-1) and markers of myeloid cells (CD11b) and pan macrophages (CD68). Thus markers of macrophage polarization could be viewed as the noninvasive "liquid biopsy" in the presence of various intrinsic kidney diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::692aab488ec9ce202bbda64dcfe192dbTest
https://pubmed.ncbi.nlm.nih.gov/31212026Test

المؤلفون: Yi Zhang, H Zhang, Fa-juan Cheng, Ping Hou, Yuan-yuan Qi, Xu-jie Zhou, M.-H. Zhao

مصطلحات موضوعية: 0301 basic medicine, Untranslated region, Adult, Male, Immunology, Lupus nephritis, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Severity of Illness Index, 03 medical and health sciences, Ikaros Transcription Factor, 0302 clinical medicine, Rheumatology, Asian People, Polymorphism (computer science), medicine, Odds Ratio, Immunology and Allergy, SNP, Humans, Genetic Predisposition to Disease, Genetic association, 030203 arthritis & rheumatology, Genetics, General Medicine, Middle Aged, Protective Factors, medicine.disease, Phenotype, Lupus Nephritis, 030104 developmental biology, Logistic Models, Case-Control Studies, Expression quantitative trait loci, Female, 5' Untranslated Regions

الوصف: Objectives: Polymorphisms of IKAROS family zinc finger 1 (IKZF1) have been found to be associated with systemic lupus erythematosus (SLE) by genome-wide association studies (GWAS). The aim of the current study was to investigate the association between IKZF1 functional variants and lupus nephritis (LN) in a northern Han Chinese population and analyse their relationship with clinical and pathological phenotypes in LN. Method: The association between IKZF1 functional variants and LN was analysed for the lead variant rs1456896 with both GWAS and expression quantitative trait loci (eQTL) top hits in 500 LN patients and 500 healthy controls. Replication was conducted in an independent cohort comprising 798 LN patients and 704 healthy controls. Using the ENCODE (Encyclopedia of DNA Elements) databases, functional annotations and differential gene expression data were evaluated. Results: A significant association between the single nuclear polymorphism (SNP) rs1456896 and susceptibility to LN was observed in the two different cohorts (p = 9.32 × 10−3 and p = 3.00 × 10−2) and reinforced in combination (p = 1.36 × 10−3). In silico analysis indicates that rs1456896 is a regulatory variant and lower mRNA expressions of IKZF1 were observed in both peripheral blood mononuclear cells (PBMCs) and renal biopsies from SLE patients compared to normal controls. Although patients with the protective genotype AA of rs1456896 seemed to have more pronounced clinical manifestations and a lower ratio of histological classes III and IV, no significant associations between rs1456896 genotypes and sub-phenotypes of LN were detected. Conclusions: Our results suggest that the rs1456896 A allele is associated with protective susceptibility to LN. However, this association did not seem to be implicated in the disease and histopathological severity of LN in the current population.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fafc1b60284d5743e773295b8305ebcfTest