Norio Kusumoto

Proviral loads of human T-lymphotropic virus Type 1 in asymptomatic carriers with different infection routes

High human T‐lymphotropic virus Type 1 (HTLV‐1) proviral DNA load (PVL) has been reported to be one risk factor for the development of adult T‐cell leukemia/lymphoma (ATL). ATL is also believed to develop in HTLV‐1 carriers who acquire infection perinatally. ATL cells have been reported to frequently harbor defective provirus. In our study, PVLs for three different regions of HTLV‐1 provirus (5′LTR‐gag, gag and pX) were measured in 309 asymptomatic carriers with different infection routes. PVLs for the pX region in 21 asymptomatic carriers with maternal infection was significantly higher than in 24 carriers with spousal infection. Among 161 carriers with relatively high pX PVLs (equal to or greater than 1 copy per 100 peripheral blood mononuclear cells), 26 carriers (16%) had low gag PVL/pX PVL (less than 0.5) and four (2%) had low 5′LTR‐gag PVL/pX PVL (less than 0.5). Low gag PVL/pX PVL ratio, which reflects deficiency and/or polymorphism of HTLV‐1 proviral DNA sequences for the gag region, was also associated with maternal infection. These data suggest that HTLV‐1 carriers with maternal infection tend to have high PVLs, which may be related to provirus with deficiency and/or the polymorphism of proviral DNA sequences. In addition, there is a possibility that this ratio may be used as a tool to differentiate the infection routes of asymptomatic HTLV‐1 carriers, which supports the need for a large scale study.

Use of anti-tumor necrosis factor biologics in the treatment of rheumatoid arthritis does not change human T-lymphotropic virus type 1 markers: a case series

Abstract Anti-tumor necrosis factor (anti-TNF) biologics are effective in the treatment of rheumatoid arthritis (RA); however, it is still not clear whether this treatment promotes the development of malignancies such as lymphoma. Human T-lymphotropic virus type 1 (HTLV-1), which is a causative agent of adult T-cell lymphoma (ATL), is prevalent in Japan. Many HTLV-1-positive patients with RA are assumed to exist; however, there have thus far been no reports on the effect of anti-TNF biologics on HTLV-1-positive patients. We analyzed the response to treatment with anti-TNF biologics and change of HTLV-1 markers in two cases of RA. The two cases showed no response based on the European League Against of Rheumatism response criteria 60–96 weeks after administration of anti-TNF biologics (infliximab and etanercept). No signs of ATL were observed and HTLV-1 markers, such as proviral load and clonality of HTLV-1-infected cells, showed no significant change in either of two cases. Therefore, treatment with anti-TNF biologics did not induce activation of HTLV-1, although the effect on RA was not as effective as in HTLV-1-negative patients in this limited study. Further long-term study with a greater number of patients is necessary to clarify the safety and efficacy of anti-TNF biologics in HTLV-1-positive patients with RA.

FRI0194 Treatment with anti-tumor necrosis factor (TNF) biologics to human t-lymphotropic virus type 1 (HTLV-1) positive patients with rheumatoid arthritis (RA): a case-control study

Objectives To see whether the clinical features and responses to anti-TNF of HTLV-1 positive patients with RA are different from those of HTLV-1 negative patients. Methods The clinical features and response to anti-TNF were compared between 10 female HTLV-1 positive RA patients and 20 age-matched female HTLV-1 negative patients, who were diagnosed based on the 1987 ACR criteria for RA. Therapeutics response was evaluated using the EULAR improvement criteria. Results Significantly higher baseline level of C-reactive protein (CRP) was observed in HTLV-1 positive patients than in HTLV-1 positive patients (P = 0.003). The value of disease activity score in 28 joints (DAS28) and the levels of erythrocyte sedimentation rate (ESR) tended to be higher in HTLV-1 positive patients. The discontinuation rate of anti-TNF was higher in HTLV-1 positive patients 6 months after the beginning of treatment than in HTLV-1 negative patients (30 % v.s 0 %, respectively). Most of reason for discontinuation was inefficacy of anti-TNF. EULAR response rate in 3 months of the treatment was worse in HTLV-1 positive patients than in HTLV-1 positive patients. The levels of CRP, ESR and the value of DAS28 remained to be significantly higher in carrier RA than non-carrier RA. There is no development of lymphoma or myelopathy during 2-years observation period in HTLV-1 positive patients. Conclusions The result of this small study suggested that HTLV-1 positive RA patients have high inflammation and resistance to the treatment with anti-TNF. Further study with larger number of cases is necessary to confirm these data. Disclosure of Interest None Declared