The switch from proteasome to immunoproteasome is increased in circulating cells of patients with fast progressive immunoglobulin A nephropathy and associated with defective CD46 expression

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F21%3A10434518" target="_blank" >RIV/00216208:11110/21:10434518 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/21:10434518

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=26IFomC.fD" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=26IFomC.fD</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/ndt/gfaa092" target="_blank" >10.1093/ndt/gfaa092</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The switch from proteasome to immunoproteasome is increased in circulating cells of patients with fast progressive immunoglobulin A nephropathy and associated with defective CD46 expression

Popis výsledku v původním jazyce

The proteasome to immunoproteasome (iPS) switch consists of beta 1, beta 2 and beta 5 subunit replacement by low molecular weight protein 2 (LMP2), LMP7 and multicatalytic endopeptidase-like complex-1 (MECL1) subunits, resulting in a more efficient peptide preparation for major histocompatibility complex 1 (MHC-I) presentation. It is activated by toll-like receptor (TLR) agonists and interferons and may also be influenced by genetic variation. In a previous study we found an iPS upregulation in peripheral cells of patients with immunoglobulin A nephropathy (IgAN). We aimed to investigate in 157 IgAN patients enrolled through the multinational Validation Study of the Oxford Classification of IgAN (VALIGA) study the relationships between iPS switch and estimated glomerular filtration rate (eGFR) modifications from renal biopsy to sampling. Patients had a previous long follow-up (6.4years in median) that allowed an accurate calculation of their slope of renal function decline. We also evaluated the effects of the PSMB8/PSMB9 locus (rs9357155) associated with IgAN in genome-wide association studies and the expression of messenger RNAs (mRNAs) encoding for TLRs and CD46, a C3 convertase inhibitor, acting also on T-regulatory cell promotion, found to have reduced expression in progressive IgAN. We detected an upregulation of LMP7/beta 5 and LMP2/beta 1 switches. We observed no genetic effect of rs9357155. TLR4 and TLR2 mRNAs were found to be significantly associated with iPS switches, particularly TLR4 and LMP7/beta 5 (P&lt;0.0001). The LMP7/beta 5 switch was significantly associated with the rate of eGFR loss (P=0.026), but not with eGFR at biopsy. Fast progressors (defined as the loss of eGFR &gt;75th centile, i.e. -1.91mL/min/1.73m(2)/year) were characterized by significantly elevated LMP7/beta 5 mRNA (P=0.04) and low CD46 mRNA expression (P&lt;0.01). A multivariate logistic regression model, categorizing patients by different levels of kidney disease progression, showed a high prediction value for the combination of high LMP7/beta 5 and low CD46 expression.

Název v anglickém jazyce

The switch from proteasome to immunoproteasome is increased in circulating cells of patients with fast progressive immunoglobulin A nephropathy and associated with defective CD46 expression

Popis výsledku anglicky

The proteasome to immunoproteasome (iPS) switch consists of beta 1, beta 2 and beta 5 subunit replacement by low molecular weight protein 2 (LMP2), LMP7 and multicatalytic endopeptidase-like complex-1 (MECL1) subunits, resulting in a more efficient peptide preparation for major histocompatibility complex 1 (MHC-I) presentation. It is activated by toll-like receptor (TLR) agonists and interferons and may also be influenced by genetic variation. In a previous study we found an iPS upregulation in peripheral cells of patients with immunoglobulin A nephropathy (IgAN). We aimed to investigate in 157 IgAN patients enrolled through the multinational Validation Study of the Oxford Classification of IgAN (VALIGA) study the relationships between iPS switch and estimated glomerular filtration rate (eGFR) modifications from renal biopsy to sampling. Patients had a previous long follow-up (6.4years in median) that allowed an accurate calculation of their slope of renal function decline. We also evaluated the effects of the PSMB8/PSMB9 locus (rs9357155) associated with IgAN in genome-wide association studies and the expression of messenger RNAs (mRNAs) encoding for TLRs and CD46, a C3 convertase inhibitor, acting also on T-regulatory cell promotion, found to have reduced expression in progressive IgAN. We detected an upregulation of LMP7/beta 5 and LMP2/beta 1 switches. We observed no genetic effect of rs9357155. TLR4 and TLR2 mRNAs were found to be significantly associated with iPS switches, particularly TLR4 and LMP7/beta 5 (P&lt;0.0001). The LMP7/beta 5 switch was significantly associated with the rate of eGFR loss (P=0.026), but not with eGFR at biopsy. Fast progressors (defined as the loss of eGFR &gt;75th centile, i.e. -1.91mL/min/1.73m(2)/year) were characterized by significantly elevated LMP7/beta 5 mRNA (P=0.04) and low CD46 mRNA expression (P&lt;0.01). A multivariate logistic regression model, categorizing patients by different levels of kidney disease progression, showed a high prediction value for the combination of high LMP7/beta 5 and low CD46 expression.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30217 - Urology and nephrology

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Nephrology, Dialysis, Transplantation

ISSN

0931-0509

e-ISSN

—

Svazek periodika

36

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

1389-1398

Kód UT WoS článku

000715360500008

EID výsledku v databázi Scopus

2-s2.0-85089119728