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

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 predominant...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 2022-05, Vol.33 (5), p.908-917
Main Authors: Zachova, Katerina, Jemelkova, Jana, Kosztyu, Petr, Ohyama, Yukako, Takahashi, Kazuo, Zadrazil, Josef, Orsag, Jiri, Matousovic, Karel, Galuszkova, Dana, Petejova, Nadezda, Mestecky, Jiri, Raska, Milan
Format: Article
Language:English
Subjects:
Basic Research
Female
Galactose
Glomerulonephritis, IGA
Humans
Immunoglobulin A - metabolism
Immunoglobulin G
Immunoglobulin M
Male
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Summary: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 light (L) chains, but the nature and origin of such IgA remains enigmatic. We analyzed 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). In comparison to HCs and non-IgAN patients, peripheral blood surface/membrane bound (mb)-Gd-IgA1 cells from IgAN patients express predominantly L chains. In contrast, total mb-IgA , mb-IgG , and mb-IgM cells were preferentially positive for kappa ( ) L chains, in all analyzed groups. Although minor in comparison to L chains, 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 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. Peripheral blood of IgAN patients is enriched with migratory 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.
ISSN:1046-6673
1533-3450
DOI:10.1681/asn.2021081086