Intrarenal cytokine gene expression in lupus nephritis

Abstract

Lupus nephritis is characterised by intrarenal inflammation and lymphocyte activation. To examine the profile of cytokine gene expression in glomerulus and tubulointerstitium in patients with lupus nephritis. 36 consecutive patients with systemic lupus erythematosus having active renal disease were recruited, and they were required to undergo kidney biopsy. Glomerular and tubulointestitial cytokine expression of interleukin (IL)2, 4, 10, 12, 18, interferon gamma (IFN)gamma, T-bet (the Th1 transcription factor), GATA-3 (the Th2 transcription factor), transforming growth factor beta and monocyte chemoattractant protein (MCP)1 were studied by laser microdissection of the renal biopsy specimen, followed by real-time quantitative PCR. There were 13 patients with World Health Organization class III nephritis, 14 patients with class IV nephritis and 9 patients with class V nephritis. There was a significant correlation between serum C3, C4 and anti-double strand DNA antibody level with glomerular expression of T-bet, IFNgamma and IL2. There was a significant correlation between histological activity index and glomerular expression of IL12, IL18, IL10 and MCP1. In addition, the degree of glomerular leucocyte infiltration significantly correlated with glomerular expression of IFNgamma, IL10, IL12 and IL18. By contrast, histological chronicity index correlated with the tubulointerstitial expression of IL2, MCP1 and GATA-3. Intraglomerular expression of certain target genes correlate with the severity of systemic as well as histological activity, whereas the tubulointerstitial expression of other target genes correlate with the degree of chronic kidney scarring. This result may shed light on the immunopathogenesis of lupus nephritis.