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

Birmann, Okayama Akihiko, Kim Norma, Arisawa Kokichi, Breen, Carneiro-Proietti, Falk, Hanchard Barrie, Inoue Manami, Martínez-Maza Otoniel, Murphy, Pfeiffer, Sawada Takashi, Stuver, Tsugane Shoichiro, Li Hongchuan, Suppan, Mueller, Hisada Michie

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• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 3
• Langue: English

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Birmannet al.Retrovirology2011,8(Suppl 1):A81 http://www.retrovirology.com/content/8/S1/A81

M E E T I N GA B S T R A C TOpen 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 1* 23 45 Brenda M Birmann, Akihiko Okayama , Norma Kim , Kokichi Arisawa , Elizabeth C Breen , 6 78 910 Anna B F CarneiroProietti , Kerstin I Falk , Barrie Hanchard , Manami Inoue , Otoniel MartínezMaza, 11 1213 149 15,16 Edward L Murphy, Ruth M Pfeiffer, Takashi Sawada, Sherri O Stuver, Shoichiro Tsugane , Hongchuan Li, 1 1712,18 Catherine A Suppan , Nancy E Mueller, Michie Hisada From15th International Conference on Human Retroviruses: HTLV and Related Viruses Leuven and Gembloux, Belgium. 58 June 2011

Background Adult Tcell leukemia/lymphoma (ATL) is a rare and often fatal outcome of infection with human Tlympho tropic 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 regres sion, 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 inter leukin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

* Correspondence: [e-mail] 1 Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, 02115, USA Full list of author information is available at the end of the article

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) activa tion, 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 repli cation 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.

Author details 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, 3 University of Miyazaki, Miyazaki, Japan.RTI International, Rockville, Maryland, 4 20852, USA.Department of Preventive Medicine, Institute of Health 5 Biosciences, Tokushima University, Tokushima, Japan.Cousins Center for Psychoneuroimmunology, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California 6 Los Angeles, Los Angeles, California, 90095, USA.Hemominas Foundation, 7 Belo Horizonte, Minas Gerais, Brazil.Department of Preparedness, Swedish Institute for Communicable Disease Control and MTC, Karolinska Institute, 8 Stockholm, Sweden.Department of Pathology, University of the West 9 Indies, Mona Kingston, Jamaica. Research Center for Cancer Prevention and

© 2011 Birmann et al; licensee 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.