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

Katerina Zachova, Jana Jemelkova, Petr Kosztyu, Yukako Ohyama, Kazuo Takahashi, Josef Zadrazil, Jiri Orsag, Karel Matousovic, Dana Galuszkova, Nadezda Petejova, Jiri Mestecky, Milan Raska

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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 l light (L) chains, but the nature and origin of such IgA remains enigmatic. Methods We analyzed l 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-IgA11 cells from IgAN patients express predominantly l L chains. In contrast, total mb-IgA1, mb- IgG1, and mb-IgM1 cells were preferentially positive for kappa (k) L chains, in all analyzed groups. Although minor in comparison to k L chains, l L chain subsets of mb-IgG1, mb-IgM1, and mb-IgA1 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 l1 mb-Gd-IgA11, CCR101, and CCR91 cells, which preferentially home to the upper respiratory and digestive tracts. Furthermore, we observed that mb-Gd-IgA11 cell populations comprise more CD1381 cells and plasmablasts (CD381) in comparison to total mb-IgA1 cells. Conclusions Peripheral blood of IgAN patients is enriched with migratory l1 mb-Gd-IgA11 B cells, with the potential to home to mucosal sites where Gd-IgA1 could be produced during local respiratory or digestive tract infections.

Original languageEnglish
Pages (from-to)908-917
Number of pages10
JournalJournal of the American Society of Nephrology
Volume33
Issue number5
DOIs
Publication statusPublished - 05-2022

All Science Journal Classification (ASJC) codes

  • Nephrology

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