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  • Meeting abstract
  • Open Access

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

  • 1Email author,
  • 2,
  • 3,
  • 4,
  • 5,
  • 6,
  • 7,
  • 8,
  • 9,
  • 10,
  • 11,
  • 12,
  • 13,
  • 14,
  • 9,
  • 15, 16,
  • 1,
  • 17 and
  • 12, 18
Retrovirology20118 (Suppl 1) :A81

https://doi.org/10.1186/1742-4690-8-S1-A81

  • Published:

Keywords

  • Virus Type
  • Blood Draw
  • Serologic Marker
  • Conditional Logistic Regression
  • Host Immunity

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.

Declarations

Acknowledgements

This abstract is presented on behalf of the ATL Cohort Consortium.

Authors’ Affiliations

(1)
Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
(2)
Department of Rheumatology, Infectious Diseases and Laboratory Medicine, University of Miyazaki, Miyazaki, Japan
(3)
RTI International, Rockville, Maryland 20852, USA
(4)
Department of Preventive Medicine, Institute of Health Biosciences, Tokushima University, Tokushima, Japan
(5)
Cousins Center for Psychoneuroimmunology, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California 90095, USA
(6)
Hemominas Foundation, Belo Horizonte, Minas Gerais, Brazil
(7)
Department of Preparedness, Swedish Institute for Communicable Disease Control and MTC, Karolinska Institute, Stockholm, Sweden
(8)
Department of Pathology, University of the West Indies, Mona Kingston, Jamaica
(9)
Research Center for Cancer Prevention and Screening, National Cancer Center, Japan
(10)
Departments of Obstetrics and Gynecology, and Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, and Department of Epidemiology, UCLA School of Public Health, , University of California Los Angeles, Los Angeles, California 90095, USA
(11)
Departments of Laboratory Medicine and Epidemiology/Biostatistics, University of California San Francisco and Blood Systems Research Institute, San Francisco, California 94118, USA
(12)
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892, USA
(13)
Department of Clinical Development, Oncology Product Creation Unit, Eisai Co. Ltd, Tokyo, Japan
(14)
Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts 02118, USA
(15)
Laboratory of Experimental Immunology, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, NIH, DHHS, Frederick, MD 21702, USA
(16)
Basic Research Program, SAIC-Frederick Inc., National Cancer Institute-Frederick, Frederick, MD 21702, USA
(17)
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA
(18)
Current affiliation: Takeda Global Research and Development Center, Inc, Deerfield, Illinois 60015, USA

Copyright

© Birmann et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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