Antiviral immune response against HTLV-1 invalidates T-SPOT.TB ® results in patients with HTLV-1-positive rheumatic diseases.

Autor:	Kimura M; Division of Respirology, Rheumatology, Infectious Diseases and Neurology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan., Umekita K; Division of Respirology, Rheumatology, Infectious Diseases and Neurology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan.; Clinical Laboratory, University of Miyazaki of Hospital, Miyazaki, Japan., Iwao C; Division of Respirology, Rheumatology, Infectious Diseases and Neurology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan., Kawano K; Clinical Laboratory, University of Miyazaki of Hospital, Miyazaki, Japan., Hashikura Y; Clinical Laboratory, University of Miyazaki of Hospital, Miyazaki, Japan., Hashiba Y; Institute of Rheumatology, Miyazaki Zenjinkai Hospital, Miyazaki, Japan., Hidaka T; Institute of Rheumatology, Miyazaki Zenjinkai Hospital, Miyazaki, Japan., Sugata K; Division of Genomics and Transcriptomics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan., Satou Y; Division of Genomics and Transcriptomics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan., Miyazaki T; Division of Respirology, Rheumatology, Infectious Diseases and Neurology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Oct 29; Vol. 15, pp. 1480506. Date of Electronic Publication: 2024 Oct 29 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1480506
Abstrakt:	Background: T-SPOT.TB ® , one of the screening tests for latent tuberculosis infection (LTBI), yields invalid results in human T-cell leukemia virus type 1 (HTLV-1)-positive patients with rheumatoid arthritis. However, the detailed mechanisms behind this invalidation are unclear. Additionally, it remains unclear whether T-SPOT.TB ® or QuantiFERON-TB (QFT) is more useful in HTLV-1-positive patients with rheumatic disease (RD). Method: Among all of the HTLV-1-positive RD patients who visited our department between August 2012 and December 2022, 44 patients who were screened using T-SPOT.TB® were included in the analysis. QFT testing was performed in 33 of the 44 patients, and the results were compared with that of T-SPOT.TB®. Furthermore, we performed a culture experiment mimicking T-SPOT.TB® using peripheral blood mononuclear cells (PBMCs) obtained from HTLV-1-positive patients with RD. Additionally, T-cell subsets with autonomous product IFN-γ were analyzed using a flow cytometer. Results: Of the included patients, 13 (29.5%) were invalid for T-SPOT.TB® because of the increased number of negative control spots. The median HTLV-1 proviral load in the invalid group was higher than that in the valid group (2.45 vs. 0.49 copies/100 PBMCs, respectively, p = 0.002). QFT was performed in all 33 patients, including 13 patients who were invalid in T-SPOT.TB®. The main source of IFN-γ production was CD8+ T-cells in the T-SPOT.TB® mimic experiment. Furthermore, Tax-expressing CD4+ T-cells and Tax-specific cytotoxic CD8+ T-cells were more frequently observed in patients with invalid results than in patients with valid results. CD4+ T-cell depletion in the T-SPOT.TB® mimic experiment reduced the population of IFN-γ producing CD8+ T cells. Conclusion: T-SPOT.TB® may be invalidated by the interaction between Tax-expressing CD4+ T-cells and cytotoxic CD8+ T-cells. Moreover, HTLV-1-associated immune reactions due to contact between these cells may be unlikely to occur in QFT using whole blood. Therefore, our results reveal the superiority of QFT over T-SPOT.TB® as a screening test for LTBI in HTLV-1-positive patients with RD. Competing Interests: TH received honoraria for lectures from AbbVie GK, Eli Lilly Japan K.K., Pfizer Japan Inc., Asahi Kasei Pharma Corp., Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K.,Taisho Pharma Co., Ltdand Eisai Co. K. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Kimura, Umekita, Iwao, Kawano, Hashikura, Hashiba, Hidaka, Sugata, Satou and Miyazaki.)
Databáze:	MEDLINE
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