title: Th1/Th2 predominance and proinflammatory cytokines determine the clinicopathological severity of IgA nephropathy.
abstract: BACKGROUND
  IgA nephropathy is one of the most common forms of primary glomerulonephritis in adults. Its pathogenesis is complex. The nature of infiltrating and proliferating cells and of cellular mediators could contribute to the progression of IgA nephropathy towards end-stage renal failure.
  
  
  METHODS
  To evaluate this hypothesis, we attempted to quantify the magnitude of intrarenal gene expression of various cytokines (IL-1 beta, TNF-alpha, IL-6, IL-15, IL-2, IFN-gamma, IL-10) and chemokines (IL-8, RANTES, MCP-1) in 48 renal core biopsy specimens, diagnosed as IgA nephropathy by immunofluorescence microscopy. Semi-quantitative reverse-transcriptase polymerase chain reaction using internal competitors was used for the quantification of gene transcripts.
  
  
  RESULTS
  The expression of intrarenal gene transcripts of various cytokines and chemokines was closely interrelated, but not associated with the pathological grading system. The IFN-gamma/IL-10 ratio was higher in patients with renal dysfunction than in those with normal renal function (P=0.0483). Gene transcript levels of proinflammatory cytokines were related to the amount of proteinuria. In patients with severe glomerular sclerosis, the ratio of IFN-gamma/IL-10 gene transcripts was high (P=0.04). IL-10 gene transcript level was related to the severity of tubulointerstitial damage. The levels of gene expression of IL-10 (P=0.009), IFN-gamma (P=0.03), and TNF-alpha (P=0.005) were related to the degree of mesangial matrix expansion and the extent of intrarenal arteriolar changes correlated with the expression of the IL-8 gene transcript (r=0.43, P=0.004).
  
  
  CONCLUSIONS
  We propose that Th1/Th2 predominance and the level of proinflammatory cytokines could determine the pathogenetic processes and the severity of the clinical manifestations of IgA nephropathy.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: C S
authors.initials: CS
authors.lastname: Lim
authors.forename: S
authors.initials: S
authors.lastname: Zheng
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
authors.forename: C
authors.initials: C
authors.lastname: Ahn
authors.forename: J S
authors.initials: JS
authors.lastname: Han
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: J S
authors.initials: JS
authors.lastname: Lee
authors.forename: D W
authors.initials: DW
authors.lastname: Chae
authors.forename: J R
authors.initials: JR
authors.lastname: Koo
authors.forename: R W
authors.initials: RW
authors.lastname: Chun
authors.forename: J W
authors.initials: JW
authors.lastname: Noh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators