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

Autor:	Sallustio F; Department of Interdisciplinary Medicine, University of Bari 'Aldo Moro', Bari, Italy., Curci C; Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.; Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University 'Aldo Moro', Bari, Italy., Chaoul N; Allergology Unit, Department of Emergency and Organ Transplantation, University 'Aldo Moro', Bari, Italy., Fontò G; Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University 'Aldo Moro', Bari, Italy., Lauriero G; Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University 'Aldo Moro', Bari, Italy., Picerno A; Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University 'Aldo Moro', Bari, Italy., Divella C; Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University 'Aldo Moro', Bari, Italy., Di Leo V; Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University 'Aldo Moro', Bari, Italy., De Angelis M; Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Bari, Italy., Ben Mkaddem S; Faculty of Medicine, Center for Research on Inflammation, Paris Diderot University, INSERM U1149, ELR8252 CNRS, Paris, France., Macchia L; Allergology Unit, Department of Emergency and Organ Transplantation, University 'Aldo Moro', Bari, Italy., Gallone A; Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy., Monteiro RC; Faculty of Medicine, Center for Research on Inflammation, Paris Diderot University, INSERM U1149, ELR8252 CNRS, Paris, France., Pesce F; Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University 'Aldo Moro', Bari, Italy., Gesualdo L; Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University 'Aldo Moro', Bari, Italy.
Jazyk:	angličtina
Zdroj:	Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association [Nephrol Dial Transplant] 2021 Feb 20; Vol. 36 (3), pp. 452-464.
DOI:	10.1093/ndt/gfaa264
Abstrakt:	Background: 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. Methods: 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. Results: 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 in IgAN but not in patients with other glomerulonephritides. Conclusions: Our results demonstrate a significant difference in the amount of intestinal-activated B lymphocytes between IgAN patients and HSs, confirming the hypothesis of the pathogenic role of intestinal mucosal hyperresponsiveness in IgAN. The intestinal-renal axis plays a crucial role in IgAN and several factors may contribute to its complex pathogenesis and provide an important area of research for novel targeted therapies to modulate progression of the disease. (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)
Databáze:	MEDLINE
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