GalNAc-T14 may Contribute to Production of Galactose-Deficient Immunoglobulin A1, the Main Autoantigen in IgA Nephropathy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F23%3A73621430" target="_blank" >RIV/61989592:15110/23:73621430 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00098892:_____/23:10157909

Výsledek na webu

<a href="https://www.kireports.org/article/S2468-0249(23)01169-5/fulltext" target="_blank" >https://www.kireports.org/article/S2468-0249(23)01169-5/fulltext</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ekir.2023.02.1072" target="_blank" >10.1016/j.ekir.2023.02.1072</a>

Jazyk výsledku

angličtina

Název v původním jazyce

GalNAc-T14 may Contribute to Production of Galactose-Deficient Immunoglobulin A1, the Main Autoantigen in IgA Nephropathy

Popis výsledku v původním jazyce

Introduction: Immunoglobulin A1 (IgA1) with galactose-deficient O-glycans (Gd-IgA1) play a key role in thepathogenesis of IgA nephropathy (IgAN). Mucosal-tissue infections increase IL-6 production and, in patientswith IgAN, are often associated with macroscopic hematuria. IgA1-secreting cell lines derived fromthe circulation of patients with IgAN, compared to those of healthy controls (HCs), produce more IgA1 thathas O-glycans with terminal or sialylated N-acetylgalactosamine (GalNAc). GalNAc residues are added toIgA1 hinge region by some of the 20 GalNAc transferases, the O-glycosylation-initiating enzymes.Expression of GALNT2, encoding GalNAc-T2, the main enzyme initiating IgA1 O-glycosylation, is similar incells derived from patients with IgAN and HCs. In this report, we extend our observations of GALNT14overexpression in IgA1-producing cell lines from patients with IgAN.Methods: GALNT14 expression was analyzed in peripheral blood mononuclear cells (PBMCs) from patientswith IgAN and from HCs. Moreover, the effect of GALNT14 overexpression or knock-down on Gd-IgA1production in Dakiki cells was assessed.Results: GALNT14 was overexpressed in PBMCs from patients with IgAN. IL-6 increased GALNT14expression in PBMCs from patients with IgAN and HCs. We used IgA1-producing cell line Dakiki, a previouslyreported model of Gd-IgA1-producing cells, and showed that overexpression of GalNAc-T14enhanced galactose deficiency of IgA1, whereas siRNA-mediated GalNAc-T14 knock-down reduced it.GalNAc-T14 was localized in trans-Golgi network, as expected.Conclusions: Overexpression of GALNT14 due to inflammatory signals during mucosal infections maycontribute to overproduction of Gd-IgA1 in patients with IgAN.

Název v anglickém jazyce

GalNAc-T14 may Contribute to Production of Galactose-Deficient Immunoglobulin A1, the Main Autoantigen in IgA Nephropathy

Popis výsledku anglicky

Introduction: Immunoglobulin A1 (IgA1) with galactose-deficient O-glycans (Gd-IgA1) play a key role in thepathogenesis of IgA nephropathy (IgAN). Mucosal-tissue infections increase IL-6 production and, in patientswith IgAN, are often associated with macroscopic hematuria. IgA1-secreting cell lines derived fromthe circulation of patients with IgAN, compared to those of healthy controls (HCs), produce more IgA1 thathas O-glycans with terminal or sialylated N-acetylgalactosamine (GalNAc). GalNAc residues are added toIgA1 hinge region by some of the 20 GalNAc transferases, the O-glycosylation-initiating enzymes.Expression of GALNT2, encoding GalNAc-T2, the main enzyme initiating IgA1 O-glycosylation, is similar incells derived from patients with IgAN and HCs. In this report, we extend our observations of GALNT14overexpression in IgA1-producing cell lines from patients with IgAN.Methods: GALNT14 expression was analyzed in peripheral blood mononuclear cells (PBMCs) from patientswith IgAN and from HCs. Moreover, the effect of GALNT14 overexpression or knock-down on Gd-IgA1production in Dakiki cells was assessed.Results: GALNT14 was overexpressed in PBMCs from patients with IgAN. IL-6 increased GALNT14expression in PBMCs from patients with IgAN and HCs. We used IgA1-producing cell line Dakiki, a previouslyreported model of Gd-IgA1-producing cells, and showed that overexpression of GalNAc-T14enhanced galactose deficiency of IgA1, whereas siRNA-mediated GalNAc-T14 knock-down reduced it.GalNAc-T14 was localized in trans-Golgi network, as expected.Conclusions: Overexpression of GALNT14 due to inflammatory signals during mucosal infections maycontribute to overproduction of Gd-IgA1 in patients with IgAN.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Kidney International Reports

ISSN

2468-0249

e-ISSN

—

Svazek periodika

2023

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

"1068–1075"

Kód UT WoS článku

000999007500001

EID výsledku v databázi Scopus

2-s2.0-85150766012