High levels of gut-homing immunoglobulin A+ B lymphocytes support the pathogenic role of intestinal mucosal hyperresponsiveness in immunoglobulin A nephropathy patients.

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
Fabio SallustioLoreto Gesualdo

Abstract

Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulonephritis. The role of the microbiota and mucosal immunity in the pathogenesis of IgAN remains a key element. To date, the hypothetical relationship between commensal bacteria, elevated tumour necrosis factor (TNF) superfamily member 13 [also known as B-cell activating factor (BAFF)] levels, perturbed homoeostasis of intestinal-activated B cells and intestinal IgA class switch has not been clearly shown in IgAN patients. We studied the intestinal-renal axis connections, analysing levels of BAFF, TNF ligand superfamily member 13 (APRIL) and intestinal-activated B cells in IgAN patients, healthy subjects (HSs) and patients with non-IgA glomerulonephritides. IgAN patients had increased serum levels of BAFF cytokine, correlating with higher amounts of five specific microbiota metabolites, and high APRIL cytokine serum levels. We also found that subjects with IgAN have a higher level of circulating gut-homing (CCR9+ β7 integrin+) regultory B cells, memory B cells and IgA+ memory B cells compared with HSs. Finally, we found that IgAN patients had high levels of both total plasmablasts (PBs) and intestinal-homing PBs. Interestingly, PBs significantly increased i...Continue Reading

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Citations

Mar 15, 2021·Nephrology·Peipei WangZhanzheng Zhao
May 1, 2021·Journal of Personalized Medicine·Vincenzo Di LeoRenato C Monteiro
Sep 6, 2021·Current Opinion in Gastroenterology·Renato C Monteiro, Laureline Berthelot
Oct 14, 2021·Seminars in Immunopathology·Loreto GesualdoRosanna Coppo

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Methods Mentioned

BETA
transgenic
flow cytometry
enzyme-linked immunosorbent assay
ELISA
FACS

Software Mentioned

GraphPad
Flowjo
GraphPad Prism

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