Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

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

L. Peruzzi, R. Coppo, E. Cocchi, E. Loiacono, M. Bergallo, M. Bodria, L. Vergano, A. Krutova, ML. Russo, A. Amore, S. Lundberg, D. Maixerova, V. Tesar, A. Perkowska-Ptasińska, M. Durlik, D. Goumenos, M. Papasotiriou, K. Galesic, L. Toric, A....

. 2021 ; 36 (8) : 1389-1398. [pub] 20210723

Language English Country Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc22004063

The proteasome to immunoproteasome (iPS) switch consists of β1, β2 and β5 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 (6.4 years 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/β5 and LMP2/β1 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/β5 (P < 0.0001). The LMP7/β5 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 >75th centile, i.e. -1.91 mL/min/1.73 m2/year) were characterized by significantly elevated LMP7/β5 mRNA (P = 0.04) and low CD46 mRNA expression (P < 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/β5 and low CD46 expression.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22004063
003      
CZ-PrNML
005      
20220127145607.0
007      
ta
008      
220113s2021 xxk f 000 0|eng||
009      
AR
024    7_
$a 10.1093/ndt/gfaa092 $2 doi
035    __
$a (PubMed)32582935
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Peruzzi, Licia $u Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy $u Department of Nephrology, Dialysis and Transplantation, Regina Margherita Hospital, Turin, Italy
245    14
$a 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 / $c L. Peruzzi, R. Coppo, E. Cocchi, E. Loiacono, M. Bergallo, M. Bodria, L. Vergano, A. Krutova, ML. Russo, A. Amore, S. Lundberg, D. Maixerova, V. Tesar, A. Perkowska-Ptasińska, M. Durlik, D. Goumenos, M. Papasotiriou, K. Galesic, L. Toric, A. Papagianni, M. Stangou, M. Mizerska-Wasiak, L. Gesualdo, E. Montemurno, L. Benozzi, S. Cusinato, T. Hryszko, M. Klinger, D. Kamińska, M. Krajewska, VALIGA study group of the ERA-EDTA Immunonephrology Working Group
520    9_
$a The proteasome to immunoproteasome (iPS) switch consists of β1, β2 and β5 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 (6.4 years 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/β5 and LMP2/β1 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/β5 (P < 0.0001). The LMP7/β5 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 >75th centile, i.e. -1.91 mL/min/1.73 m2/year) were characterized by significantly elevated LMP7/β5 mRNA (P = 0.04) and low CD46 mRNA expression (P < 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/β5 and low CD46 expression.
650    _2
$a celogenomová asociační studie $7 D055106
650    12
$a IgA nefropatie $x genetika $7 D005922
650    _2
$a lidé $7 D006801
650    _2
$a antigeny CD46 $7 D051916
650    12
$a proteasomový endopeptidasový komplex $x genetika $x metabolismus $7 D046988
650    _2
$a messenger RNA $7 D012333
650    _2
$a upregulace $7 D015854
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Coppo, Rosanna $u Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy
700    1_
$a Cocchi, Enrico $u Department of Nephrology, Dialysis and Transplantation, Regina Margherita Hospital, Turin, Italy
700    1_
$a Loiacono, Elisa $u Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy
700    1_
$a Bergallo, Massimilano $u Department of Nephrology, Dialysis and Transplantation, Public Health and Pediatric Sciences, University of Turin, Turin, Italy
700    1_
$a Bodria, Monica $u IRCCS Istituto Giannina Gaslini, Genova, Italy
700    1_
$a Vergano, Luca $u Department of Nephrology, Dialysis and Transplantation, Regina Margherita Hospital, Turin, Italy
700    1_
$a Krutova, Alexandra $u Regional Children's Clinical Hospital, Vladivostok, Russia
700    1_
$a Russo, Maria Luisa $u Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy
700    1_
$a Amore, Alessandro $u Department of Nephrology, Dialysis and Transplantation, Regina Margherita Hospital, Turin, Italy
700    1_
$a Lundberg, Sigrid $u Department of Clinical Sciences, Nephrology, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
700    1_
$a Maixerova, Dita $u Department of Nephrology, First Faculty of Medicine and General University Hospital, Prague, Czech Republic
700    1_
$a Tesar, Vladimir $u Department of Nephrology, First Faculty of Medicine and General University Hospital, Prague, Czech Republic
700    1_
$a Perkowska-Ptasińska, Agnieszka $u Department of Transplantation Medicine and Nephrology, Warsaw Medical University, Warsaw, Poland
700    1_
$a Durlik, Magdalena $u Department of Transplantation Medicine and Nephrology, Warsaw Medical University, Warsaw, Poland
700    1_
$a Goumenos, Dimitris $u Department of Nephrology, University Hospital of Patras, Patras, Greece
700    1_
$a Papasotiriou, Marios $u Department of Nephrology, University Hospital of Patras, Patras, Greece
700    1_
$a Galesic, Kresimir $u Department of Nephrology, Dubrava University Hospital, Zagreb, Croatia
700    1_
$a Toric, Luka $u Department of Nephrology, Dubrava University Hospital, Zagreb, Croatia
700    1_
$a Papagianni, Aikaterini $u Department of Nephrology, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
700    1_
$a Stangou, Maria $u Department of Nephrology, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
700    1_
$a Mizerska-Wasiak, Malgorzata $u Department of Pediatrics and Nephrology, Medical University of Warsaw, Warsaw, Poland
700    1_
$a Gesualdo, Loreto $u Department of Nephrology, Emergency and Transplantation, University of Bari, Bari, Italy
700    1_
$a Montemurno, Eustacchio $u Department of Nephrology, Emergency and Transplantation, University of Bari, Bari, Italy
700    1_
$a Benozzi, Luisa $u Department of Nephrology, Borgomanero Hospital, Borgomanero, Italy
700    1_
$a Cusinato, Stefano $u Department of Nephrology, Borgomanero Hospital, Borgomanero, Italy
700    1_
$a Hryszko, Tomasz $u Department of Nephrology, Transplantation and Dialysis, Medical University of Bialystok, Bialystok, Poland
700    1_
$a Klinger, Marian $u Department of Internal Medicine, Opole University, Poland
700    1_
$a Kamińska, Dorota $u Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
700    1_
$a Krajewska, Magdalena $u Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
710    2_
$a VALIGA study group of the ERA-EDTA Immunonephrology Working Group
773    0_
$w MED00010288 $t Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association $x 1460-2385 $g Roč. 36, č. 8 (2021), s. 1389-1398
856    41
$u https://pubmed.ncbi.nlm.nih.gov/32582935 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20220113 $b ABA008
991    __
$a 20220127145604 $b ABA008
999    __
$a ok $b bmc $g 1751506 $s 1155212
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2021 $b 36 $c 8 $d 1389-1398 $e 20210723 $i 1460-2385 $m Nephrology, dialysis, transplantation $n Nephrol Dial Transplant $x MED00010288
LZP    __
$a Pubmed-20220113

Find record

Citation metrics

Archiving options