The effect of immunosuppressive therapy on the messenger RNA expression of target genes in the urinary sediment of patients with active lupus nephritis.
BACKGROUND
Previous studies have shown that messenger RNA (mRNA) expression of target genes is increased in the urinary sediment of patients with active lupus. We study the effect of immunosuppressive therapy on the urinary gene expression profile in patients with active lupus nephritis. Method. We recruited nine patients with active systemic lupus erythematosus (SLE) and renal disease, and required corticosteroid, with or without cytotoxic treatment. They were followed for 6 months, urine samples were collected at 0, 4, 12 and 24 weeks and gene expression profile was determined by polymerase chain reactions. The pattern of gene expression was compared to clinical parameters of therapeutic response.


RESULTS
Amongst the target genes studied, there was a progressive decline in the urinary expression of T-bet, interleukin (IL)-10, transforming growth factor-beta (TGF-beta), monocyte chemoattractant protein-1 (MCP-1), and interferon-gamma (IFN-gamma) after immunosuppressive treatment, although the change of IFN-gamma was not statistically significant. The time course of their urinary expression was parallel to the systemic activity as reflected by the systemic lupus erythematosus disease activity index (SLEDAI). Throughout the study period, the SLEDAI score correlated significantly with the expressions of IFN-gamma (r = 0.43, P = 0.009), T-bet (r = 0.40, P = 0.016), TGF-beta (r = 0.51, P = 0.002) and MCP-1 (r = 0.38, P = 0.022). The anti-double strand(anti-ds)DNA antibody titer correlated significantly with the expressions of IFN-gamma (r = 0.45, P = 0.009), T-bet (r = 0.37, P = 0.034), IL-10 (r = 0.59, P<0.001), TGF-beta (r = 0.44, P = 0.010) and MCP-1 (r = 0.49, P = 0.004). On the other hand, the expression level of IL-2, IL-4, IL-12, IL-18 and GATA-3 remained static throughout the study period.


CONCLUSIONS
The mRNA expression of T-bet, IL-10, TGF-beta, MCP-1, and probably IFN-gamma in the urinary sediment of patients with active lupus nephritis improves with successful immunosuppressive therapy, and the change in gene expression profile is in phase with the clinical disease activity. Measurement of urinary mRNA expression of target genes may be a potential non-invasive tool for the monitoring of lupus disease activity.
Chan
Rebecca Wing-Yan
RW
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, China.
Lai
Fernand Mac-Moune
FM
Li
Edmund Kwok-Ming
EK
Tam
Lai-Shan
LS
Chow
Kai-Ming
KM
Li
Philip Kam-Tao
PK
Szeto
Cheuk-Chun
CC
D000328:Adult; D015415:Biomarkers / Q000652:urine; D018932:Chemokine CCL2 / Q000652:urine; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000652:urine; D016753:Interleukin-10 / Q000652:urine; D008181:Lupus Nephritis / Q000175:diagnosis / Q000188:drug therapy* / Q000652:urine*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects*; D020825:T-Box Domain Proteins / Q000652:urine; D016212:Transforming Growth Factor beta / Q000652:urine; D000098815:T-bet Transcription Factor
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma