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

Kidney Int. 2009 Mar;75(5):536-41. doi: 10.1038/ki.2008.579. Epub 2008 Nov 26.


In order to present an antigen to T-cells, the antigen must first be degraded by proteasomes. Following exposure to interferons, some proteasome subunits (ss1,ss2,ss5) 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-kappaB 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 m(2)/day had a significant switch of the chymotryptic-like beta5 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-kappaB pathway but is associated with high levels of proteinuria, a well known risk factor for progression of IgA nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Adolescent
  • Adult
  • Antigen Presentation
  • Blood Cells
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Chymotrypsin
  • Female
  • Glomerulonephritis, IGA / enzymology
  • Glomerulonephritis, IGA / immunology
  • Humans
  • Leukocytes, Mononuclear / enzymology*
  • Leukocytes, Mononuclear / pathology
  • Male
  • Multienzyme Complexes / genetics*
  • NF-kappa B / metabolism
  • Proteasome Endopeptidase Complex / immunology*
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Subunits / genetics
  • Proteinuria
  • RNA, Messenger / analysis
  • Up-Regulation
  • Young Adult


  • Multienzyme Complexes
  • NF-kappa B
  • Protein Subunits
  • RNA, Messenger
  • Chymotrypsin
  • LMP7 protein
  • Proteasome Endopeptidase Complex