Prevalence of plasma autoantibody against cancer testis antigen NY-ESO-1 in HTLV-1 infected individuals with different c

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Prevalence of plasma autoantibody against cancer testis antigen NY-ESO-1 in HTLV-1 infected individuals with different clinical status Yasuo Shiohama1,6, Tadasuke Naito1, Toshio Matsuzaki2, Reiko Tanaka3, Takeaki Tomoyose4, Hiroshi Takashima2, Takuya Fukushima5, Yuetsu Tanaka3 and Mineki Saito1*

Abstract Background: Detection of specific immune responses against cancer/testis antigen NY-ESO-1 was recently reported in patients with adult T-cell leukemia/lymphoma (ATL) and human T-cell leukemia virus type 1 (HTLV-1)-infected asymptomatic carriers (ACs). However, the relationship of the responses with the HTLV-1 proviral load (PVL) and the levels of viral gene expression remain unclear. Findings: We measured plasma levels of autoantibodies to NY-ESO-1 immunogenic tumor antigen in HTLV-1-infected individuals with different clinical status, and in healthy controls. Data were compared to tax and HBZ mRNA levels, and PVL. Plasma anti-NY-ESO-1 antibody was detectable in 13.7% (7/51) of ACs, 29.2% (38/130) of patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), and 18.9% (10/53) of patients with ATL. Anti-NY-ESO-1 plasma levels were significantly higher in patients with HAM/TSP than in patients with ATL or ACs. Anti-NY-ESO-1 levels were not associated with PVL or the expression levels of tax and HBZ mRNA among HTLV-1-infected individuals, regardless of clinical status. Conclusions: The present results indicate the strong humoral immune response against NY-ESO-1 in natural HTLV-1 infection, irrespective of the clinical status. The higher immunoreactivity against NY-ESO-1 is not simply associated with the levels of both HTLV-1 gene expression and the number of infected cells in vivo. Rather, it might reflect chronic and generalized immune activation in infected individuals. Keywords: HTLV-1, NY-ESO-1, ATL, HAM/TSP, Monoclonal antibody, ELISA

Background Human T-cell leukemia virus type 1 (HTLV-1) is a human retrovirus associated with two distinct types of disease: a malignancy of mature CD4+ T cells called adult T-cell leukemia-lymphoma (ATL) [1–3] and a chronic inflammatory central nervous system disease, HTLV-1associated myelopathy/tropical spastic paraparesis (HAM/ TSP) [4, 5]. In HTLV-1 infection, only approximately 5% of infected persons develop ATL [6] and another 0.25–4% develop HAM/TSP [7–10]. The majority of infected * Correspondence: [email protected] 1 Department of Microbiology, Kawasaki Medical School, 577 Matsushima, Okayama 701-0192, Japan Full list of author information is available at the end of the article

individuals remain lifelong asymptomatic carriers (ACs). However, since the treatment of both ATL and HAM/TSP remains highly unsatisfactory, the development of novel therapies for these intractable diseases is warranted. Recently, the cancer/testis (CT) antigen NY-ESO-1, which was originally identified in esophageal cancer by serological expression cloning using autologous patient serum [11], has been reported to elicit both humoral and c