Influence of Cytokine and Mannose Binding Protein Gene Polymorphisms on Human T-Cell Leukemia Virus Type I (HTLV-I) Provirus Load in HTLV-I Asymptomatic Carriers Masataka Nishimura, Michiyuki Maeda, Jun-ichiro Yasunaga, Hideshi Kawakami, Ryuji Kaji, Akio Adachi, Takashi Uchiyama, and Masao Matsuoka ABSTRACT: Human T-cell leukemia virus type I (HTLV-I) provirus load differs more than 100-fold among carriers and a high provirus load in the peripheral blood mononuclear cells (PBMCs) is regarded as a risk factor for both preleukemic states and inflammatory diseases in- cluding HTLV-I-associated myelopathy (HAM). We ex- amined polymorphisms in the genes for tumor necrosis factor (TNF), TNF receptor type 1 and 2, lymphotoxin (LT)-, interleukin (IL)-1, IL-6, IL-10, monocyte che- moattractant protein (MCP)-1, and mannose binding pro- tein (ManBP) in 143 HTLV-I carriers whether these poly- morphisms affect the provirus load in the PBMCs of carriers. No significant association was observed between these polymorphisms and the provirus load. Homozygotes for a ManBP-variant allele, however, showed a tendency for the decreased number of provirus load. When com- bined, the data on the alleles of LT- and MCP-1, HTLV-I carriers having high producer alleles of both genes showed a trend for increased provirus load. These data suggest that inflammation or an active immune response may induce an increased amount of HTLV-I– infected T cells, leading to a high provirus load. Human Immunology 64, 453– 457 (2003). © American Society for Histocompatibility and Immunogenetics, 2003. Pub- lished by Elsevier Science Inc. KEYWORDS: lymphotoxin (LT)-, monocyte chemoat- tractant protein (MCP)-1, mannose binding protein (ManBP), human T-cell leukemia virus type I (HTLV-I), HTLV-I associated myelopathy (HAM) INTRODUCTION Human T-cell leukemia virus type I (HTLV-I) is an etiologic agent of adult T-cell leukemia and is also associated with various inflammatory diseases including HTLV-I–associated myelopathy (HAM) and HTLV-I uveitis (HU). The vast majority of HTLV-I–infected individuals remain asymptomatic, suggesting that HTLV-I infection alone is not sufficient to cause these disorders, and that individual differences in genetic pre- disposition may be related to the pathogenesis of HTLV- I–associated diseases. The HTLV-I provirus load in the peripheral blood mononuclear cells (PBMCs) was shown to differ more than 100-fold in HTLV-I carriers [1]. High provirus load was associated with both preleukemic states and inflammatory diseases including HAM and HU. Because an increased number of HTLV-I–infected cells seems to be one of the key events in these diseases, analysis of the mechanism by which virus load increases should give us an important clue to the pathogenesis of these diseases. Human leukocyte antigen (HLA) determines immune responses against HTLV-I and is regarded as a critical From the Departments of Clinical Neuroscience (M.N., R.K.) and Virology (A.A.), Tokushima University School of Medicine, Tokushima; Laboratory of Animal Experiments (M. Maeda), Institute for Frontier Medical Sciences, Kyoto; the Second Department of Internal Medicine (J.- i.Y.), Kumamoto University School of Medicine, Kumamoto; Third Depart- ment of Internal Medicine (H.K.), Hiroshima University School of Medicine, Hiroshima; Department of Hematology and Oncology (T.U.), Graduate School of Medicine, Kyoto University, Kyoto; and the Laboratory of Virus Immunology (M. Matsuoka), Research Center for AIDS, Virus Research Institute, Kyoto, Japan. Address reprint requests to: Dr. Masataka Nishimura, Department of Clinical Neuroscience, Tokushima University School of Medicine, Tokushima 770-8503, Japan; Tel: (+81) 88-633-7207; Fax: (+81) 88-633- 7208; ; E-mail: m_nishim@clin.med.tokushima-u.ac.jp. Received July 23, 2002; revised December 18, 2002; accepted December 18, 2002. Human Immunology 64, 453– 457 (2003) © American Society for Histocompatibility and Immunogenetics, 2003 0198-8859/03/$–see front matter Published by Elsevier Science Inc. doi:10.1016/S1098-8859(02)00829-7