2. Academic Validation
  3. CXCL13/CXCR5 axis facilitates TFH expansion and correlates with disease severity in adults with immune thrombocytopenia

CXCL13/CXCR5 axis facilitates TFH expansion and correlates with disease severity in adults with immune thrombocytopenia

  • Thromb Res. 2024 Dec:244:109196. doi: 10.1016/j.thromres.2024.109196.
Zhenyu Chen 1,  Qiaoyun Zheng 2,  Yali Wang 3,  Xing An 3,  Shimuye Kalayu Yirga 2,  Donghong Lin 4,  Qizhen Shi 5,  Meijuan Huang 6,  Yingyu Chen 7
Affiliations

Affiliations

  • 1 Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China; Medical Technology and Engineering College of Fujian Medical University, Fuzhou, Fujian, China.
  • 2 Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
  • 3 Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China; Medical Technology and Engineering College of Fujian Medical University, Fuzhou, Fujian, China; School of Medical Imaging, Fujian Medical University, Fuzhou, Fujian, China.
  • 4 Medical Technology and Engineering College of Fujian Medical University, Fuzhou, Fujian, China; Key Laboratory of Clinical Laboratory Technology for Precision Medicine (Fujian Medical University), Fujian Province University, Fuzhou, China.
  • 5 Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA; Blood Research Institute, Versiti, Milwaukee, WI, USA.
  • 6 Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China. Electronic address: huangmj163@163.com.
  • 7 Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China; Medical Technology and Engineering College of Fujian Medical University, Fuzhou, Fujian, China; School of Medical Imaging, Fujian Medical University, Fuzhou, Fujian, China; Key Laboratory of Clinical Laboratory Technology for Precision Medicine (Fujian Medical University), Fujian Province University, Fuzhou, China. Electronic address: chenyingyu@yahoo.com.
PMID: 39454362 DOI: 10.1016/j.thromres.2024.109196
Abstract

Background: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder defined by a diminished platelet count. ITP pathogenesis involves intricate changes to both cellular and humoral immunity. The pivotal roles of follicular helper T (TFH) cells in the maturations of B cells and the production of Antibodies are well-established. However, the specific role of TFH to the immunopathogenesis of ITP remain incompletely understood. This study aimed to clarify the association of CXCL13/CXCR5 axis with TFH in adults with ITP.

Methods: A total of 97 ITP patients and 41 healthy controls were enrolled. CD4+CXCR5+ TFH, CD4+CXCR5+PD-1+ TFH, CD4+CXCR5+Foxp3+ follicular regulatory T cells (TFR), and desialylated platelets in peripheral blood were measured by flow cytometry. Plasma cytokines were assessed by enzyme-linked immunosorbent assay. CD4+ T cells cocultured with chemokine CXCL13 in vitro was performed for the measurement of TFH proliferation. Intracellular production of Reactive Oxygen Species (ROS) was examined by dichlorodihydrofluorescein diacetate (DCFH-DA) probe staining.

Results: We observed a significant increase in circulating TFH and a marked decrease in circulating TFR in the entire ITP cohort. The ratio of TFH/TFR was elevated, accompanied by heightened levels of platelet desialylation, cytokines BAFF, HMGB1, and IL-21, while levels of IL-10 were downregulated in adults with ITP. Notably, patients with ITP exhibiting platelet count below 50 × 109/L had dramatically elevated levels in both chemokine CXCL13 and its receptor CXCR5+ TFH compared to those with platelet count above 100 × 109/L. High frequencies of TFH correlated with poor therapeutic response. Furthermore, in vitro CD4+ T cell proliferation assay demonstrated a CXCL13 dose-dependent increase in the frequencies in both CD4+CXCR5+ TFH and CD4+CXCR5+PD-1+ TFH from ITP patients. Intriguingly, DCFH-DA assay illustrated a significant enhancement in intracellular ROS generation in CXCR5+ T cell subsets, especially in CD4+CXCR5+PD-1+ TFH from 4 patients with ITP.

Conclusions: These results underscore the pivotal role of CXCL13/CXCR5 axis-drived TFH expansion in the pathogenesis of ITP, providing a potential disease severity biomarker.

Keywords

CXCL13/CXCR5 axis; Follicular helper T cell; Follicular regulatory T cell; Immune thrombocytopenia; Platelet.

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