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Functional Implications of Regulatory B Cells in Human IgA Nephropathy
Author(s) -
Wang Y.Y.,
Zhang L.,
Zhao P.W.,
Ma L.,
Li C.,
Zou H.B.,
Jiang Y.F.
Publication year - 2014
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12128
Subject(s) - regulatory b cells , nephropathy , flow cytometry , immunology , b cell , immunofluorescence , pathogenesis , antibody , biology , microbiology and biotechnology , medicine , pathology , endocrinology , diabetes mellitus
IgA nephropathy (Ig AN ) diagnosis remains largely based upon immunohistologic detection of IgA‐ and IgG‐containing glomerular deposits in renal mesangial cells, and little is known about the underlying pathogenic mechanisms. This study examines the putative contribution of B cell types, including the Breg type, to Ig AN pathogenesis. Twenty‐four patients with Ig AN and proteinuria (Group A: <3.5 g/24 h, n  = 13; Group B: >3.5 g/24 h, n  = 11) and 10 healthy controls were enrolled. The frequencies of B cell subtypes in venous blood were measured by flow cytometry. Galactose‐deficient IgA1 was measurement by ELISA . Needle biopsies were analysed by histology and immunofluorescence microscopy. Correlation between clinical features and B cell subtypes, including the regulatory B (Breg) cells, and Breg cell‐derived immunomodulatory cytokine IL ‐10 was assessed by Spearman's rank correlation test. Ig AN patients had significantly higher frequencies of CD 27 + CD 19 + , CD 38 + CD 19 + , CD 86 + CD 19 + and CD 5 + CD 19 + B cells than the healthy controls, but significantly lower levels of Breg cells and intracellular expression of IL ‐10 protein in the Breg subtype. Serum IgA concentration positively correlated with CD 27 + CD 19 + B cell frequency and negatively correlated with IL ‐10 + Breg cell frequency in Ig AN patients, and the percentage of CD 19 + CD 5 + CD 1d + in CD 19 + cells was negatively correlated with the level of serum Gd‐IgA1. Furthermore, the frequencies of CD 19 + CD 38 + and CD 19 + CD 86 + in the CD 19 + subpopulation negatively correlated with the estimated glomerular filtration rate of Ig AN patients. Several of the CD 19 + B cell subtypes and the IL ‐10 + Breg cells are differentially expressed in Ig AN patients and may contribute to the disease pathogenesis.

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