PMID- 21739457 OWN - NLM STAT- MEDLINE DCOM- 20120123 LR - 20151119 IS - 1096-9071 (Electronic) IS - 0146-6615 (Linking) VI - 83 IP - 9 DP - 2011 Sep TI - Molecular and clinical effects of betamethasone in human T-cell lymphotropic virus type-I-associated myelopathy/tropical spastic paraparesis patients. PG - 1641-9 LID - 10.1002/jmv.22131 [doi] AB - There is no effective therapy for human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Glucocorticoids are effective to reduce the motor disability in these patients, but its role as anti-spastic drugs is unknown. Here it is reported the use of corticosteroids in HAM/TSP. The goal was to find reliable molecular markers linked to treatment effectiveness. The clinical efficacy of corticosteroids was studied in 22 HAM/TSP. The treatment was a single dose of 7.0 mg of systemic betamethasone. Pre-treatment samples were obtained immediately before steroid administration and post-treatment samples were collected after 5 days. Neurological disability was evaluated by the Osame's Motor Disability Scales. Relative levels of Tax, Foxp3, IL-10, TGF-beta, CTLA-4, and GITR mRNA were measured and the percentage of CD4(+) Foxp3(+) and CD4(+) Tax(+) populations was quantified in PBMCs by real-time PCR and flow cytometry, respectively. The same parameters were studied in eight untreated carriers. Betamethasone treatment showed neurological improvement in 21 HAM/TSP patients, with one patient without response to treatment. This therapy was associated with a decrease in Tax mRNA load and CD4(+) Tax(+) T cells in HAM/TSP. Simultaneously, an increase in Foxp3 mRNA and CD4(+) Foxp3(+) T cell was detected in these patients. The other markers studied had no significant changes after treatment. Clinical improvement in betamethasone-treated HAM/TSP was associated with an inverse relationship between a decrease in Tax and an increase in Foxp3 at the mRNA and protein levels. These results suggest that both Tax and Foxp3 may represent potential biomarkers for drug treatment assessments in HAM/TSP. CI - Copyright (c) 2011 Wiley-Liss, Inc. FAU - Alberti, Carolina AU - Alberti C AD - Faculty of Chemical and Pharmaceutical Sciences, Department of Biochemistry and Molecular Biology, University of Chile, Santiago, Chile. FAU - Cartier, Luis AU - Cartier L FAU - Valenzuela, Maria A AU - Valenzuela MA FAU - Puente, Javier AU - Puente J FAU - Tanaka, Yuetsu AU - Tanaka Y FAU - Ramirez, Eugenio AU - Ramirez E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Med Virol JT - Journal of medical virology JID - 7705876 RN - 0 (Antigens, CD) RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (FOXP3 protein, human) RN - 0 (Forkhead Transcription Factors) RN - 0 (Gene Products, tax) RN - 0 (RNA, Messenger) RN - 9842X06Q6M (Betamethasone) SB - IM MH - Adult MH - Aged MH - Antigens, CD/blood MH - Betamethasone/administration & dosage/*therapeutic use MH - Biomarkers/blood MH - CD4-Positive T-Lymphocytes/virology MH - Cytokines/blood MH - Female MH - Flow Cytometry MH - Forkhead Transcription Factors/*blood MH - Gene Products, tax/*blood/genetics MH - *Human T-lymphotropic virus 1/drug effects/genetics/physiology MH - Humans MH - Leukocytes, Mononuclear MH - Lymphocyte Count MH - Male MH - Middle Aged MH - Paraparesis, Tropical Spastic/*drug therapy/virology MH - Polymerase Chain Reaction MH - RNA, Messenger MH - Viral Load EDAT- 2011/07/09 06:00 MHDA- 2012/01/24 06:00 CRDT- 2011/07/09 06:00 PHST- 2011/07/09 06:00 [entrez] PHST- 2011/07/09 06:00 [pubmed] PHST- 2012/01/24 06:00 [medline] AID - 10.1002/jmv.22131 [doi] PST - ppublish SO - J Med Virol. 2011 Sep;83(9):1641-9. doi: 10.1002/jmv.22131.