Background/Purpose: Human T cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL). ATL is an aggressive T-cell malignancy caused by HTLV-1 infection and often occurs in HTLV-1-endemic areas, such as southwestern Japan, the Caribbean islands, Central and South America, Intertropical Africa, and Middle East. Recent study indicated that the estimated annual number of new HTLV-1 infection was 4,190 in nationwide blood donor surveillance in Japan. However, it is still not clear that the prevalence of HTLV-1 infection in patients with RA. Additionally, there are questions as to whether comorbidity of RA and its treatment in HTLV-1 carriers could increase the risk of developing ATL. The aim of this study is to clarify the prevalence of HTLV-1 infection in RA patients in HTLV-1 endemic area Miyazaki, Japan. In addition, we investigated the risk factors of developing ATL in HTLV-1 positive RA patients.

Methods: We established HTLV-1 positive RA cohort study in Miyazaki from 2012. Eight hundred sixty-one patients with RA were registered in this cohort until 2015. We evaluated blood levels in HTLV-1 proviral load (PVL) samples by real-time PCR, HTLV-1 antibody titer by particle agglutination assay, and the level of soluble IL-2 receptor (sIL-2R) by ELISA.

Results: The prevalence of HTLV-1 infection in RA patients was 6.0 % in this cohort. The age of HTLV-1 positive RA patients was higher than in HTLV-1 negative RA patients (p= 0.003). In the distribution of PVL, 20% of HTLV-1 positive RA patients showed highly PVL (> 4%), which was the known risk factor for ATL. The levels of sIL-2R in sera correlated to the levels of PVL, significantly (p=0.01). Treatment of disease modifying anti-rheumatic drugs (DMARDs) including biologics were administrated in the all patients. No effect to the levels of PVL and sIL-2R by the treatment with DMARDs was observed. A patient developed chronic type ATL, who were treated with MTX and anti-TNF inhibitor during 3-years observation periods (121 person-years) in this cohort.

Conclusion: The prevalence of HTLV-1 infection in RA patients in this cohort tended to be higher than that in nationwide surveillance in Japan. The incidence of ATL in HTLV-1 carriers was estimated to one per 1000 person-years. The incidence of ATL in HTLV-1 positive RA patients was higher than that in their study, although the sample size was small. A long-term follow-up of HTLV-1 positive RA patients is required to resolve whether the comorbidity of RA and its treatment increase the risk of developing ATL.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-risk-factors-of-developing-adult-t-cell-leukemia-atl-in-human-t-cell-leukemia-virus-type-1-htlv-1-positive-patients-with-rheumatoid-arthritis-in-endemic-area-japan-a-retrospective-cohort-stu/