Katerina Zachova1,2, Jana Jemelkova1, Petr Kosztyu1,2,3, Yukako Ohyama4, Kazuo Takahashi4, Josef Zadrazil5, Jiri Orsag5, Karel Matousovic6, Dana Galuszkova7, Nadezda Petejova5,8, Jiri Mestecky9,10, Milan Raska11,2,3. 1. Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic. 2. Department of Immunology, University Hospital Olomouc, Olomouc, Czech Republic. 3. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic. 4. Department of Biomedical Molecular Sciences, School of Medicine, Fujita Health University, Nagoya, Aichi, Japan. 5. Department of Internal Medicine III Nephrology, Rheumatology, and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. 6. Department of Medicine, Second School of Medicine, Charles University, Prague and University Hospital Motol, Prague, Czech Republic. 7. Department of Transfusion Medicine, University Hospital Olomouc, Olomouc, Czech Republic. 8. Department of Internal Medicine, University Hospital Ostrava, Ostrava, Czech Republic. 9. Departments of Microbiology and Medicine, University of Alabama at Birmingham, Birmingham, Alabama milan.raska@upol.cz mestecky@uab.edu. 10. Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic. 11. Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic milan.raska@upol.cz mestecky@uab.edu.
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 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.
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.
Authors: Petr Kosztyu; Martin Hill; Jana Jemelkova; Lydie Czernekova; Leona Raskova Kafkova; Miroslav Hruby; Karel Matousovic; Karel Vondrak; Josef Zadrazil; Ivan Sterzl; Jiri Mestecky; Milan Raska Journal: Kidney Blood Press Res Date: 2018-03-06 Impact factor: 2.687
Authors: Koshi Yamada; Zhi Qiang Huang; Milan Raska; Colin Reily; Joshua C Anderson; Hitoshi Suzuki; Krzysztof Kiryluk; Ali G Gharavi; Bruce A Julian; Christopher D Willey; Jan Novak Journal: Kidney Dis (Basel) Date: 2020-04-16
Authors: Taylor Person; R Glenn King; Dana V Rizk; Jan Novak; Todd J Green; Colin Reily Journal: J Interferon Cytokine Res Date: 2022-07-06 Impact factor: 3.657