PMID- 16449281 OWN - NLM STAT- MEDLINE DCOM- 20061122 LR - 20151119 IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 21 IP - 6 DP - 2006 Jun TI - The effect of immunosuppressive therapy on the messenger RNA expression of target genes in the urinary sediment of patients with active lupus nephritis. PG - 1534-40 AB - 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. FAU - Chan, Rebecca Wing-Yan AU - Chan RW AD - Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, China. FAU - Lai, Fernand Mac-Moune AU - Lai FM FAU - Li, Edmund Kwok-Ming AU - Li EK FAU - Tam, Lai-Shan AU - Tam LS FAU - Chow, Kai-Ming AU - Chow KM FAU - Li, Philip Kam-Tao AU - Li PK FAU - Szeto, Cheuk-Chun AU - Szeto CC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060131 PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Biomarkers) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Immunosuppressive Agents) RN - 0 (RNA, Messenger) RN - 0 (T-Box Domain Proteins) RN - 0 (T-box transcription factor TBX21) RN - 0 (Transforming Growth Factor beta) RN - 130068-27-8 (Interleukin-10) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adult MH - Biomarkers/urine MH - Chemokine CCL2/urine MH - Drug Monitoring/*methods MH - Female MH - Gene Expression Profiling MH - Gene Expression Regulation/*drug effects MH - Humans MH - Immunosuppressive Agents/*pharmacology/therapeutic use MH - Interferon-gamma/urine MH - Interleukin-10/urine MH - Lupus Nephritis/diagnosis/*drug therapy/*urine MH - Middle Aged MH - RNA, Messenger/analysis/*drug effects MH - T-Box Domain Proteins/urine MH - Transforming Growth Factor beta/urine EDAT- 2006/02/02 09:00 MHDA- 2006/12/09 09:00 CRDT- 2006/02/02 09:00 PHST- 2006/02/02 09:00 [pubmed] PHST- 2006/12/09 09:00 [medline] PHST- 2006/02/02 09:00 [entrez] AID - gfk102 [pii] AID - 10.1093/ndt/gfk102 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2006 Jun;21(6):1534-40. doi: 10.1093/ndt/gfk102. Epub 2006 Jan 31.