Association of Platelet Desialylation and Circulating Follicular Helper T Cells in Patients With Thrombocytopenia

Abstract

Thrombocytopenia is a multifactorial condition that frequently involves concomitant defects in platelet production and clearance. The physiopathology of low platelet count in thrombocytopenia remains unclear. Sialylation on platelet membrane glycoprotein and follicular helper T cells (TFHs) are thought to be the novel platelet clearance pathways. The aim of this study was to clarify the roles of platelet desialylation and circulating TFHs in patients with immune thrombocytopenia (ITP) and non-ITP thrombocytopenia. We enrolled 190 patients with ITP and 94 patients with non-ITP related thrombocytopenia including case of aplastic anemia (AA) and myelodysplastic syndromes (MDS). One hundred and ten healthy volunteers were included as controls. We found significantly increased desialylated platelets in patients with ITP or thrombocytopenia in the context of AA and MDS. Platelet desialylation was negatively correlated with platelet count. Meanwhile, the circulating TFH levels in patients with thrombocytopenia were significantly higher than those of normal controls, and were positively correlated with desialylated platelet levels. Moreover, TFHs-related chemokine CXCL13 and apoptotic platelet levels were abnormally high in ITP patients. The upregulation of pro-apoptotic proteins and the activation of the MAPK/mTOR pathway were observed in the same cohort. These findings suggested that platelet desialylation and circulating TFHs may become the potential biomarkers for evaluating the disease process associated with thrombocytopenia in patients with ITP and non-ITP.

Imbalance of follicular regulatory T (Tfr) cells/follicular helper T (Tfh) cells in adult patients with primary immune thrombocytopenia

“…Similar to the findings in SLE 26 and UC 27 patients, this study showed Tfr/Tfh imbalance in untreated ITP patients. This is also consistent with the results by Chen et al 28 This imbalance manifests as an increase in Tfh cells and may further promote the Tfh-mediated B-cell response, 29,30 leading to the production of excessive antibodies, mediating the destruction of PLT, and possibly inducing or promoting the occurrence of ITP. However, the above studies did not further explore the imbalance of Tfr/Tfh cells in peripheral blood of ITP patients after treatment.…”

Obinutuzumab‐induced acute thrombocytopenia: Report of two cases and review of literature

“…13 Autoreactive anti-GPIbα antibodies can induce Fc-independent platelet activation and desialylation responsible for platelet clearance. [14][15][16] A similar side effect has been reported with rituximab, although less frequently. Omura et al 6 reported a case of "Rituximab-Induced Acute Thrombocytopenia".…”

“…Finally, drug‐dependent antibodies (DDA) have also been reported as a mechanism of immune‐mediated and drug‐induced thrombocytopenia 13 . Autoreactive anti‐GPIbα antibodies can induce Fc‐independent platelet activation and desialylation responsible for platelet clearance 14–16 …”

Association of thrombocytopenia with immune checkpoint inhibitors: a large-scale pharmacovigilance analysis based on the data from FDA adverse event reporting system database

“…Platelets from patients expressed significantly higher levels of mTOR and its phosphorylated proteins than healthy controls, indicating aberrant activation of mTOR pathways. ( Chen et al, 2022 ). In previous studies, the mTOR inhibitor rapamycin was reported to reduce drug toxicity and reverse treatment resistance in combination with ICIs ( Beeram et al, 2007 ; Esfahani et al, 2019 ), showing therapeutic potential against ICIs-induced ITP.…”