What question did this study set out to answer?

To investigate the mechanism by which a loss-of-function variant in GALNT14 contributes to the development of IgA nephropathy.

March 18, 2025Journal of Clinical InvestigationOpen Access

Loss of GalNAc-T14 links O-glycosylation defects to alterations in B cell homing in IgA nephropathy

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Authors

SPSindhuri PrakashColumbia University Irving Medical Center NSNicholas J. SteersColumbia University Irving Medical Center YLYifu LiCentral South University

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Implication

Functional genetic study shows that GalNAc-T14 deficiency impairs B cell homing and promotes glomerular IgA deposition in mice, indicating a systemic role for O-glycosylation in IgA nephropathy.

Key Points

To investigate the mechanism by which a loss-of-function variant in GALNT14 contributes to the development of IgA nephropathy.
Identified a family with IgA nephropathy segregating a heterozygous loss-of-function variant in GALNT14 and quantified carrier serum IgA1 O-glycosylation.
Generated Galnt14-null mice and evaluated serum IgA concentrations, ex vivo B cell IgA secretion, colonic mucin thickness, and glomerular IgA deposition with aging and following sterile colitis.
Performed adoptive-transfer experiments using spleen-derived Galnt14-deficient B lymphocytes to assess in vivo homing efficiency and peripheral blood retention.
Galnt14-null mice exhibited increased serum IgA levels and elevated ex vivo B cell IgA production, developing age-dependent and colitis-induced glomerular IgA deposition.
Galnt14 deficiency reduced the colonic mucin layer and caused a systemic redistribution of IgA-producing cells away from mucosal compartments.
Adoptive transfer demonstrated impaired homing of Galnt14-deficient B lymphocytes, leading to increased retention of these cells in the peripheral circulation.

Cite This Study

Prakash et al. (2025) studied this question.

synapsesocial.com/papers/6a88324b60f64afcf1608b33 https://doi.org/10.1172/jci181164

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Implication

Functional genetic study shows that GalNAc-T14 deficiency impairs B cell homing and promotes glomerular IgA deposition in mice, indicating a systemic role for O-glycosylation in IgA nephropathy.

Loss of GalNAc-T14 links O-glycosylation defects to alterations in B cell homing in IgA nephropathy

Discussion

Member takes

Implication

Key Points

Cite This Study

Loss of GalNAc-T14 links O-glycosylation defects to alterations in B cell homing in IgA nephropathy

Discussion

Member takes

Implication

Key Points

Cite This Study

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