Upregulation of the immunoproteasome in peripheral blood mononuclear cells of patients with IgA nephropathy

Rosanna Coppo, Roberta Camilla, Alda Alfarano, Sabrina Balegno, Domenico Mancuso, Licia Peruzzi, Alessandro Amore, Antonio Dal Canton, Vincenzo Sepe, Pierangelo Tovo

Research output: Contribution to journalArticlepeer-review

Abstract

In order to present an antigen to T-cells, the antigen must first be degraded by proteasomes. Following exposure to interferons, some proteasome subunits (β1,β2,β5) are replaced by others (LMP2, LMP7, MECL-1) that have more optimal catalytic properties for peptide presentation; this more efficient organelle is termed the immuno-proteasome. Here we measured gene expression of various subunits in peripheral mononuclear cells of patients with IgA nephropathy, a disease with features of immune dysregulation. We used quantitative PCR to measure the expression of proteasomal subunit mRNA in mononuclear cells from IgA nephropathy patients, a group of proteinuric control patients with idiopathic nephrotic syndromes, and healthy controls. A significant switch in the expression of trypsin- and chymotrypsin-like proteasome subunits to corresponding immuno-proteasome subunits was found in patients as compared to healthy controls. Further, we found that nuclear translocation of NF-κB p50 and p65 was significantly greater in the IgA nephropathy patients, but this did not correlate with the switch to the immuno-proteasome phenotype. Patients with proteinuria greater than 0.5 g/1.73 m2/day had a significant switch of the chymotryptic-like β5 protease to the LMP7 subunit, but this did not occur in patients with idiopathic nephrotic syndrome. The switch to an immuno-proteasome in peripheral blood mononuclear cells of patients with IgA nephropathy suggests an increased efficiency of antigen processing and presentation. This switch appears to be independent of a coincidental activation of the NF-κB pathway but is associated with high levels of proteinuria, a well known risk factor for progression of IgA nephropathy.

Original languageEnglish
Pages (from-to)536-541
Number of pages6
JournalKidney International
Volume75
Issue number5
DOIs
Publication statusPublished - Mar 2009

Keywords

  • IgA nephropathy
  • Immunoproteasome
  • NF-κB
  • Proteasome
  • Proteinuria
  • Transcription factors

ASJC Scopus subject areas

  • Nephrology

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