Intrarenal cytokine gene expression in lupus nephritis.
BACKGROUND
Lupus nephritis is characterised by intrarenal inflammation and lymphocyte activation.


OBJECTIVE
To examine the profile of cytokine gene expression in glomerulus and tubulointerstitium in patients with lupus nephritis.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Chan
Rebecca Wing-Yan
RW
Department of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Lai
Fernand Mac-Moune
FM
Li
Edmund Kwok-Ming
EK
Tam
Lai-Shan
LS
Chow
Kai-Ming
KM
Lai
Ka-Bik
KB
Li
Philip Kam-Tao
PK
Szeto
Cheuk-Chun
CC
D000328:Adult; D018932:Chemokine CCL2 / Q000032:analysis / Q000652:urine; D016207:Cytokines / Q000032:analysis* / Q000652:urine; D005260:Female; D050990:GATA3 Transcription Factor / Q000032:analysis / Q000652:urine; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000652:urine; D007378:Interleukins / Q000032:analysis / Q000652:urine; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D007684:Kidney Tubules / Q000276:immunology / Q000473:pathology; D007962:Leukocytes / Q000276:immunology; D008181:Lupus Nephritis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D020825:T-Box Domain Proteins / Q000032:analysis / Q000652:urine; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000652:urine; D000098815:T-bet Transcription Factor
D018932:Chemokine CCL2; D016207:Cytokines; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D007378:Interleukins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma