title: Combined C4d and CD3 immunostaining predicts immunoglobulin (Ig)A nephropathy progression.
abstract: A number of molecules have been shown recently to be involved in the pathogenesis and progression of immunoglobulin (Ig)A nephropathy (IgAN). Among these, we have selected C4d (complement lectin pathway involvement), CD3 (T cell marker, traducing interstitial inflammation), transglutaminase 2 (TGase-2, involved in tissue fibrosis development) and p-extracelluar-regulated kinase (ERK)1/2 (protein kinase intracellular signaling molecule) to perform a panel of immunohistological biomarkers and assess its predictive value for disease progression. Immunohistochemical staining of these biomarkers was performed in paraffin sections from 74 renal biopsy cases with the clinical diagnosis of IgAN. Association between score analysis of these parameters and disease course was assessed through univariate and multivariate analysis, including baseline clinical and histological data. Univariate analysis showed that glomerular C4d, tubulointerstitial TGase2 and CD3 scores were associated with baseline proteinuria and disease progression. Multivariate analysis showed that only baseline estimated glomerular filtration rate (eGFR), C4d and CD3 were associated independently with progressive kidney disease (decline of at least 50% in the eGFR or progression to end-stage renal disease (ESRD) during the follow-up period). Establishing an accurate prediction model for IgAN progression is still a matter of research in clinical nephrology. The complement system, particularly lectin pathway activation, and T cell activation, have been shown previously to be potential modifiers of the disease course. Here we show that the combination of two histological biomarkers (C4d and CD3) can be a powerful predictor of IgAN progression and a potential useful tool for the clinical approach of this disease.
authors.affiliation: Nephrology and Infectious Disease R&D Group, INEB, I3S, University of Porto, Porto, Portugal; Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Faria
authors.forename: C
authors.initials: C
authors.lastname: Henriques
authors.forename: A C
authors.initials: AC
authors.lastname: Matos
authors.forename: M R
authors.initials: MR
authors.lastname: Daha
authors.forename: M
authors.initials: M
authors.lastname: Pestana
authors.forename: M
authors.initials: M
authors.lastname: Seelen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000276:immunology* / Q000378:metabolism; D003181:Complement C4 / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000276:immunology; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000276:immunology / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology / Q000378:metabolism; D008954:Models, Biological; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D017252:CD3 Complex; D003181:Complement C4; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: T cells; autoimmunity; complement