Altered Host Immunity, Human T Lymphotropic Virus Type I Replication, and Risk of Adult T-Cell Leukemia/Lymphoma: A Prospective Analysis from the ATL Cohort Consortium

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Altered Host Immunity, Human T Lymphotropic Virus Type I Replication, and Risk of Adult T-Cell Leukemia/Lymphoma: A Prospective Analysis from the ATL Cohort Consortium

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Title: Altered Host Immunity, Human T Lymphotropic Virus Type I Replication, and Risk of Adult T-Cell Leukemia/Lymphoma: A Prospective Analysis from the ATL Cohort Consortium
Author: Okayama, Akihiko; Kim, Norma; Arisawa, Kokichi; Hanchard, Barrie; Inoue, Manami; Sawada, Takashi; Tsugane, Shoichiro; Li, Hongchuan; Hisada, Michie; Birmann, Brenda Melanie; Mueller, Nancy Elsa; Martínez-Maza, Otoniel; Breen, Elizabeth C.; Carneiro-Proietti, Anna B. F.; Falk, Kerstin I.; Murphy, Edward L.; Pfeiffer, Ruth M.; Stuver, Sherri O.; Suppan, Catherine A.

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Citation: Birmann, Brenda Melanie, Akihiko Okayama, Norma Kim, Kokichi Arisawa, Elizabeth C. Breen, Anna B. F. Carneiro-Proietti, Kerstin I. Falk, et al. 2011. Altered host immunity, human T lymphotropic virus type I replication, and risk of adult T-cell leukemia/lymphoma: A prospective analysis from the ATL Cohort Consortium. Retrovirology 8(S1): A81.
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Abstract: Background: Adult T-cell leukemia/lymphoma (ATL) is a rare and often fatal outcome of infection with human T-lymphotropic virus type I (HTLV-I). Altered host immunity in HTLV-I carriers has been postulated as a risk factor for ATL, but is not well understood. Methods: We prospectively examined well-validated serologic markers of HTLV-I pathogenesis and host immunity in 53 incident ATL cases and 150 carefully matched asymptomatic HTLV-I carriers from eight population-based studies in Japan, Jamaica, the United States and Brazil. We used multivariable conditional logistic regression, conditioned on the matching factors (cohort/race, age, sex, and sample collection year), to evaluate the biomarkers’ associations with ATL in all subjects and by years (≤5, >5) from blood draw to ATL diagnosis. Results: In the pooled population, above-median soluble interleukin-2-receptor-alpha levels (sIL2R, v. ≤ median; odds ratio (OR), 95% confidence interval (CI)=4.08, 1.47-11.29) and anti-Tax seropositivity (anti-Tax; OR, 95% CI=2.97, 1.15-7.67), which indicate T cell activation and HTLV-I replication, respectively, were independently associated with an increased ATL risk. Above-median total immunoglobulin E levels (v. ≤ median; OR, 95% CI=0.45, 0.19-1.06), which indicate type 2 (B cell) activation, predicted a lower ATL risk. The sIL2R and anti-Tax associations with ATL were stronger in samples collected ≤5 years pre-diagnosis. Conclusions: The biomarker profile predictive of ATL risk suggests a role for heightened T cell activation and HTLV-I replication and diminished type 2 immunity in the etiology of ATL in HTLV-I carriers. Translation of these findings to clinical risk prediction or early ATL detection requires further investigation. Acknowledgements: This abstract is presented on behalf of the ATL Cohort Consortium.
Published Version: doi:10.1186/1742-4690-8-S1-A81
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112798
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:8808828
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