Immunological Pattern in IgA Nephropathy.

Clara Esteve Cols,Bibiana Quirant Sánchez,Helena Marco Rusiñol,Maruja Isabel Navarro Díaz,Freddzia-Amanda Graterol Torres,Jordi Ara Del Rey,Eva Mª Martínez Cáceres

doi:10.3390/ijms21041389

Abstract

The current gold-standard diagnostic technique for IgA nephropathy (IgAN), the leading form of primary glomerulonephritis, is renal biopsy. CD89 (the main IgA receptor) is expressed on the surface of monocytes and plays a role in disease pathogenesis. Immunocomplexes formed by sCD89 (soluble form) and Gd-IgA1 are related to disease prognosis. We hypothesize that reduced CD89 surface expression on monocytes may be a marker of disease severity. We aimed to analyze leukocyte subpopulations in peripheral blood and CD89 surface expression on monocytes in a prospective study of 22 patients and 12 healthy subjects (HS). Leukocyte subpopulations and CD89 expression were analyzed by flow cytometry. IgAN patients had a higher percentage of activated and effector memory CD4+ and CD8+ T lymphocytes, a lower percentage of transitional B lymphocytes and plasmablasts, and a higher percentage of CD56dimCD16+ NK cells and myeloid dendritic cells compared with HS. Correlations between reduced CD89 expression levels on nonclassical monocytes, histological findings of a poor prognosis on renal biopsy and baseline renal function were observed. IgAN patients show a characteristic immunological pattern in peripheral blood. A reduced expression level of CD89 on nonclassical monocytes identifies patients with a worse renal prognosis.

Highlights

IgA nephropathy (IgAN), the leading primary glomerulonephritis worldwide, is a significant cause of renal disease, leading to end-stage renal disease (ESRD) in up to 40% of patients about 30–40 years after diagnosis [1,2,3,4]
IgAN patients had a higher absolute number of lymphocytes compared with healthy subjects (HS) (Patients: 2258 ± 253.7 lymphocytes/μL; HS: 1773 ± 80.71 lymphocyte/μL; p = 0.0209)
Percentage of CD8+ and CD4+ T lymphocytes were lower in IgAN patients (23.37 ± 1.754% CD8+; 47.94 ± 2.027% CD4+) compared with HS (31.33 ± 1.126% CD8+; 62.28 ± 1.368% CD4+; p = 0.0003 and p < 0.0001, respectively)

Summary

Introduction

IgA nephropathy (IgAN), the leading primary glomerulonephritis worldwide, is a significant cause of renal disease, leading to end-stage renal disease (ESRD) in up to 40% of patients about 30–40 years after diagnosis [1,2,3,4]. The diagnosis of IgAN remains biopsy-proven, based on pathological criteria, including mesangial IgA deposits identified by direct immunofluorescence. The central finding of the physiopathogenic process in patients with IgAN is the presence of degalactosylated IgA1 (Gd-IgA1) [6] This abnormal molecule (Gd-IgA1) may induce the generation of autoantibodies, inducing immune complexes formation. These complexes (composed of Gd-IgA1 and IgG linked the o-glycan hinge region of Gd-IgA1 [6,7]), are deposited in the glomerular mesangium, causing complement activation and renal damage. Gd-IgA1 molecules tend to aggregate, forming polymeric molecules [9] These circulating polymeric Gd-IgA1 molecules induce the shedding of the extracellular domain of CD89, and Gd-IgA1-CD89 immune complexes

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