Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
BMC Immunol. 2023 Apr 7;24(1):6. doi: 10.1186/s12865-023-00541-8.
Primary immune thrombocytopenia (ITP) is characterized for the skewed Th differentiation towards Th1 and Th17 cells as well as the impaired number and function of regulatory T cells (Tregs). Tregs are capable of co-expressing effector Th markers in different inflammatory milieu, which probably indicates Treg dysfunction and incompetence to counter over-activated immune responses.
Ninety-two primary ITP patients from March 2013 to December 2018 were included, and proinflammatory plasticity in different Treg compartments, age groups, and TGFBR2 variant carrier status were investigated.
Patients were categorized into elderly (n = 44) and younger (n = 48) groups according to an age of 50 years at disease onset. The overall remission rate was 82.6% after first-line regimens, including 47.8% complete remission. TGFBR2 variants were found in 7 (7.6%) patients with three V216I and four T340M heterozygote carriers. ITP patients demonstrated elevated co-expression of IL-17 and decreased co-expression of both IFN-γ and IL-13 than health control (all p < 0.01). The elderly group demonstrated elevated prevalence of TGFBR2 variants (p = 0.037) and elevated co-expression of IL-17 (p = 0.017) in Tregs, while female predominance was found in the younger group (p = 0.037). In the elderly group, TGFBR2 variant carriers demonstrated further elevated co-expression of IL-17 (p = 0.023) and decreased co-expression of both IFN-γ (p = 0.039) and IL-13 (p = 0.046) in the aTreg compartment.
Our findings revealed additional aberrations of Treg proinflammatory plasticity in elderly primary ITP patients, and highlighted the potential role of Treg dysfunction and senescence in the pathogenesis and management among these patients.
原发免疫性血小板减少症（ITP）的特征是 Th 分化向 Th1 和 Th17 细胞倾斜，以及调节性 T 细胞（Treg）的数量和功能受损。Treg 在不同的炎症环境中能够共表达效应 Th 标志物，这可能表明 Treg 功能障碍和无能以对抗过度激活的免疫反应。
纳入 2013 年 3 月至 2018 年 12 月的 92 例原发性 ITP 患者，研究不同 Treg 区室、年龄组和 TGFBR2 变体携带者状态的促炎可塑性。
根据发病时年龄将患者分为老年（n=44）和年轻（n=48）组。一线方案治疗后总体缓解率为 82.6%，完全缓解率为 47.8%。发现 7 例（7.6%）患者存在 TGFBR2 变异，其中 3 例为 V216I，4 例为 T340M 杂合子携带者。与健康对照相比，ITP 患者 Treg 中 IL-17 的共表达增加，IFN-γ 和 IL-13 的共表达减少（均 p<0.01）。老年组 Tregs 中 TGFBR2 变异的发生率较高（p=0.037），IL-17 的共表达较高（p=0.017），而年轻组女性居多（p=0.037）。在老年组中，TGFBR2 变体携带者的 aTreg 区室中 IL-17 的共表达进一步增加（p=0.023），IFN-γ（p=0.039）和 IL-13（p=0.046）的共表达减少。
我们的研究结果揭示了老年原发性 ITP 患者 Treg 促炎可塑性的额外异常，并强调了 Treg 功能障碍和衰老在这些患者发病机制和治疗中的潜在作用。
