Galactose-Deficient IgA1 B cells in the Circulation of IgA Nephropathy Patients Carry Preferentially Lambda Light Chains and Mucosal Homing Receptors
Copyright © 2022 by the American Society of Nephrology..
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.
| Errataetall: |
CommentIn: J Am Soc Nephrol. 2022 May;33(5):873-875. - PMID 35393339 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Journal of the American Society of Nephrology : JASN - 33(2022), 5 vom: 03. Mai, Seite 908-917 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zachova, Katerina [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.05.2022 Date Revised 02.05.2023 published: Print-Electronic CommentIn: J Am Soc Nephrol. 2022 May;33(5):873-875. - PMID 35393339 Citation Status MEDLINE |
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| doi: |
10.1681/ASN.2021081086 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM336479948 |
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| 245 | 1 | 0 | |a Galactose-Deficient IgA1 B cells in the Circulation of IgA Nephropathy Patients Carry Preferentially Lambda Light Chains and Mucosal Homing Receptors |
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| 500 | |a Date Completed 03.05.2022 | ||
| 500 | |a Date Revised 02.05.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: J Am Soc Nephrol. 2022 May;33(5):873-875. - PMID 35393339 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 by the American Society of Nephrology. | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
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