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 language | English |
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Pages (from-to) | 536-541 |
Number of pages | 6 |
Journal | Kidney International |
Volume | 75 |
Issue number | 5 |
DOIs | |
Publication status | Published - Mar 2009 |
Keywords
- IgA nephropathy
- Immunoproteasome
- NF-κB
- Proteasome
- Proteinuria
- Transcription factors
ASJC Scopus subject areas
- Nephrology