title: Differential patterns of serum biomarkers of immune activation in human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis, and adult T-cell leukemia/lymphoma.
abstract: Adult T-cell leukemia/lymphoma (ATL) and human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are associated with differing patterns of immune dysfunction. Biomarkers of immune activation may correlate with perturbations of immune function associated with these diseases. We conducted a pilot cross-sectional study to assess four candidate biomarkers of immune activation. beta 2-microglobulin, neopterin, tryptophan, and kynurenine levels were assayed in stored sera from asymptomatic, human T-cell leukemia virus type I (HTL V-I)-seronegative (HTLV-I-) and HTLV-I-seropositive (HTLV-I+) individuals, and ATL and HAM/TSP patients previously enrolled in seroepidemiological studies in Jamaica. Mean levels of beta 2-microglobulin, neopterin, and kynurenine were significantly elevated among ATL patients compared to the other study groups. Mean tryptophan levels were significantly lower among ATL and HAM/TSP patients than HTLV-I- and HTLV-I+ groups. No significant differences in biomarkers were found between the HTLV-I- and HTLV-I+ groups. Among HAM/TSP patients, a significant association was found between elevated neopterin levels and symptoms of less than 4 years duration. In Cox proportional hazards regression modeling, neopterin and tryptophan were found to be independent predictors of survival among ATL patients. This study demonstrates a differential pattern of biomarkers of immune activation among ATL and HAM/TSP patients compared to HTLV-I- and HTLV-I+ individuals. Neopterin and tryptophan may be useful clinical indicators of disease severity and prognosis among HAM/TSP and ATL patients.
authors.affiliation: Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Giusti
authors.forename: E M
authors.initials: EM
authors.lastname: Maloney
authors.forename: B
authors.initials: B
authors.lastname: Hanchard
authors.forename: O S
authors.initials: OS
authors.lastname: Morgan
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: H
authors.initials: H
authors.lastname: Wachter
authors.forename: E
authors.initials: E
authors.lastname: Williams
authors.forename: B
authors.initials: B
authors.lastname: Cranston
authors.forename: D
authors.initials: D
authors.lastname: Fuchs
authors.forename: A
authors.initials: A
authors.lastname: Manns
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005544:Forecasting; D015481:HTLV-I Antibodies / Q000097:blood; D006801:Humans; D007563:Jamaica; D007737:Kynurenine / Q000097:blood; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019798:Neopterin; D015493:Paraparesis, Tropical Spastic / Q000097:blood / Q000276:immunology*; D010865:Pilot Projects; D016016:Proportional Hazards Models; D016036:Seroepidemiologic Studies; D015996:Survival Rate; D014364:Tryptophan / Q000097:blood; D001613:beta 2-Microglobulin / Q000032:analysis
chemical_list: D015415:Biomarkers; D015481:HTLV-I Antibodies; D001613:beta 2-Microglobulin; D001708:Biopterins; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan