Changes in mucosa-associated invariant t cells (mait), associated cytokines, and mr-1+ cell number and phenotype in the peripheral blood of pediatric itp patients with and without eltrombopag therapy

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia caused by the formation of antibodies against platelets. Mucosa-associated invariant T cells (MAIT), a subset of unconventional T cells present in the blood and mucosa, are activated in an MR-1-mediated manner, respond to certain infections and cytokines and produce various effector cytokines. In this study, changes in blood MAIT cells were investigated in pediatric ITP patients who received and did not receive Eltrombopag. Twenty healthy volunteers (n:20), 60 untreated, and 16 treated patients (with Eltrombopag) were included in the study. PBMCs isolated using the Ficoll-Hypaque density gradient were stained with appropriate surface markers and subjected to flow cytometric analysis. In addition, intracellular cytokine staining was performed to measure the level of IFN-γ, IL17A, IL-22, TNF-α cytokines after PMA/Ionomycin stimulation, and all data were analyzed using FlowJo and GraphPad 8. Independent of Eltrombopag treatment, MAIT cell absolute counts were decreased in ITP patients. CD45RO levels of the CD8+MAIT subtype increased, αβ+ T cells decreased, and γδ+ T cell frequency increased in ITP patients. In patients, the frequency of MAIT cell-derived IFN-γ and TNF-α decreased, MR-1 expression, which is responsible for MAIT cell activation in the CD3−fraction, increased, and this level decreased to the levels in healthy controls in individuals receiving Eltrombopag treatment. The low HLA-DR levels seen in CD3- cells in ITP patients reached the levels of healthy controls in the group receiving Eltrombopag. These results show that the number and activation status of MAIT cells in ITP patients change and Eltrombopag treatment modulates MAIT cell activity.