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.
Front Immunol. 2024 Oct 29;15:1480506. doi: 10.3389/fimmu.2024.1480506. eCollection 2024.
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).
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.
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, = 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.
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.
T-SPOT.TB 是潜伏性结核感染（LTBI）的筛查试验之一，在人类 T 细胞白血病病毒 1 型（HTLV-1）阳性的类风湿关节炎患者中会产生无效结果。然而，导致这种无效的详细机制尚不清楚。此外，在 HTLV-1 阳性的风湿性疾病（RD）患者中，T-SPOT.TB 或 QuantiFERON-TB（QFT）哪个更有用仍不清楚。
在 2012 年 8 月至 2022 年 12 月期间我院就诊的所有 HTLV-1 阳性 RD 患者中，对 44 例使用 T-SPOT.TB®进行筛查的患者进行了分析。对 44 例患者中的 33 例进行了 QFT 检测，并将结果与 T-SPOT.TB®进行了比较。此外，我们使用来自 HTLV-1 阳性 RD 患者的外周血单个核细胞（PBMC）进行了模拟 T-SPOT.TB®的培养实验。此外，使用流式细胞仪分析了具有自主产生 IFN-γ的 T 细胞亚群。
纳入的患者中有 13 例（29.5%）因阴性对照斑点数量增加而 T-SPOT.TB®无效。无效组的 HTLV-1 前病毒载量高于有效组（分别为 2.45 与 0.49 拷贝/100 PBMC， = 0.002）。对所有 33 例患者进行了 QFT 检测，其中包括 13 例 T-SPOT.TB®无效的患者。在 T-SPOT.TB®模拟实验中，IFN-γ产生的主要来源是 CD8+T 细胞。此外，在无效结果患者中，Tax 表达的 CD4+T 细胞和 Tax 特异性细胞毒性 CD8+T 细胞比有效结果患者更常见。在 T-SPOT.TB®模拟实验中，CD4+T 细胞耗竭减少了产生 IFN-γ的 CD8+T 细胞群体。
T-SPOT.TB®可能因 Tax 表达的 CD4+T 细胞与细胞毒性 CD8+T 细胞之间的相互作用而失效。此外，由于这些细胞之间的接触而引起的 HTLV-1 相关免疫反应可能不太可能在使用全血的 QFT 中发生。因此，我们的结果表明，与 T-SPOT.TB®相比，QFT 作为 HTLV-1 阳性 RD 患者 LTBI 的筛查试验具有优越性。
