Galactose-Deficient IgA1 B cells in the Circulation of IgA Nephropathy Patients Carry Preferentially Lambda Light Chains and Mucosal Homing Receptors.

Autor:	Zachova K; Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.; Department of Immunology, University Hospital Olomouc, Olomouc, Czech Republic., Jemelkova J; Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic., Kosztyu P; Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.; Department of Immunology, University Hospital Olomouc, Olomouc, Czech Republic.; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic., Ohyama Y; Department of Biomedical Molecular Sciences, School of Medicine, Fujita Health University, Nagoya, Aichi, Japan., Takahashi K; Department of Biomedical Molecular Sciences, School of Medicine, Fujita Health University, Nagoya, Aichi, Japan., Zadrazil J; Department of Internal Medicine III Nephrology, Rheumatology, and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic., Orsag J; Department of Internal Medicine III Nephrology, Rheumatology, and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic., Matousovic K; Department of Medicine, Second School of Medicine, Charles University, Prague and University Hospital Motol, Prague, Czech Republic., Galuszkova D; Department of Transfusion Medicine, University Hospital Olomouc, Olomouc, Czech Republic., Petejova N; Department of Internal Medicine III Nephrology, Rheumatology, and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.; Department of Internal Medicine, University Hospital Ostrava, Ostrava, Czech Republic., Mestecky J; Departments of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, Alabama.; Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic., Raska M; Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.; Department of Immunology, University Hospital Olomouc, Olomouc, Czech Republic.; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
Jazyk:	angličtina
Zdroj:	Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2022 May; Vol. 33 (5), pp. 908-917. Date of Electronic Publication: 2022 Feb 03.
DOI:	10.1681/ASN.2021081086
Abstrakt:	Background: IgA nephropathy (IgAN) primary glomerulonephritis is characterized by the deposition of circulating immune complexes composed of polymeric IgA1 molecules with altered O-glycans (Gd-IgA1) and anti-glycan antibodies in the kidney mesangium. The mesangial IgA deposits and serum IgA1 contain predominantly λ light (L) chains, but the nature and origin of such IgA remains enigmatic. Methods: We analyzed λ L chain expression in peripheral blood B cells of 30 IgAN patients, 30 healthy controls (HCs), and 18 membranous nephropathy patients selected as disease controls (non-IgAN). Results: In comparison to HCs and non-IgAN patients, peripheral blood surface/membrane bound (mb)-Gd-IgA1 + cells from IgAN patients express predominantly λ L chains. In contrast, total mb-IgA + , mb-IgG + , and mb-IgM + cells were preferentially positive for kappa ( κ ) L chains, in all analyzed groups. Although minor in comparison to κ L chains, λ L chain subsets of mb-IgG + , mb-IgM + , and mb-IgA + cells were significantly enriched in IgAN patients in comparison to non-IgAN patients and/or HCs. In contrast to HCs, the peripheral blood of IgAN patients was enriched with λ + mb-Gd-IgA1 + , CCR10 + , and CCR9 + cells, which preferentially home to the upper respiratory and digestive tracts. Furthermore, we observed that mb-Gd-IgA1 + cell populations comprise more CD138 + cells and plasmablasts (CD38 + ) in comparison to total mb-IgA + cells. Conclusions: Peripheral blood of IgAN patients is enriched with migratory λ + mb-Gd-IgA1 + B cells, with the potential to home to mucosal sites where Gd-IgA1 could be produced during local respiratory or digestive tract infections. (Copyright © 2022 by the American Society of Nephrology.)
Databáze:	MEDLINE
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