The time-sequential changes of risk factors for adult T-cell leukemia development in human T-cell leukemia virus-positive patients with rheumatoid arthritis: a retrospective cohort study

Abstract

Objective: This study aimed to investigate the time-sequential changes of risk factors for adult T-cell leukemia (ATL) development in human T-cell leukemia virus type 1 (HTLV-1)-positive rheumatoid arthritis (RA) patients.

Methods: HTLV-1 infection was screened using particle agglutination assay and confirmed via western blotting in 365 RA patients. Twenty-three HTLV-1-positive RA patients were included in the study cohort. Blood samples were obtained from these patients at each observation time point. The values of HTLV-1 proviral load (PVL) and serum soluble IL-2 receptor (sIL2-R), which are risk factors for ATL development, were measured using real-time PCR and enzyme immunoassay, respectively.

Results: The study cohort comprised 79 person-years. The median HTLV-1 PVL and sIL2-R values of the HTLV-1-positive RA patients were 0.44 copies per 100 white blood cells (WBCs) and 406 U/mL, respectively. Three HTLV-1-positive RA patients showed a high PVL value. No remarkable changes were observed in the PVL and sIL2-R values during the observation period. However, one elderly HTLV-1-positive RA patient who had a high PVL value developed ATL during treatment with methotrexate and infliximab.

Conclusion: A thorough clinical assessment of the risk factors for ATL development may be necessary in daily clinical practice for RA patients in HTLV-1-endemic areas in Japan.

Keywords:

• Rheumatoid arthritis
• human T-cell leukemia virus type 1
• adult T-cell leukemia
• lymphoproliferative disorders
• immunosuppressive agents

Acknowledgments

We would like to thank Dr. Ikuo Yamamoto and Ms. Yuki Kaseda of the University of Miyazaki for their technical support in this work. We would like to thank Professor Eisuke Inoue of the Division of Medical Informatics, St. Marianna University School of Medicine, Kanagawa, Japan for statistical analysis support in this work. We would also like to acknowledge Ms. Michiyo Koufuku and Ms. Yumiko Kai of the Institute of Rheumatology, Zenjinkai Shimin-no-Mori Hospital for their help in data management. We would like to thank Enago (https://www.enago.jp/) for English language editing.

Conflict of Interest

None

Additional information

Funding

This work supported by a Health Labor Sciences Research Grant, and Division of Rare/Intractable Disease Project of the Japan Agency for Medical Research and Development (AMED).