EHA 2023 – Report: Biology

EHA 2023 – Report: Biology
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Among the abstracts presented on ITP biology at the last EHA 2023 annual meeting, the following are worth mentioning, concerning progresses which are being made in exploring ITP pathogenesis, and in particular megakaryocyte impairment, T cells abnormalities, mesenchymal stem cell disfunction, alterations of gut microbiota.

Yang P et al. evaluated CD4+ T cells in ITP pathogenesis, with particular focus on methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), which was found to be upregulated in CD4+ T cells of ITP patients compared to healthy controls. The inhibition of MTHFD2 reduced the proliferation and activation of CD4+ T cells, reduced the proinflammatory cytokines and increased the percentage of T regulatory cells of ITP patients in vitro; same results could be obtained with Tacrolimus treatment in mice.

Megakaryocyte desyalilation is involved in impaired platelet production in ITP. MKs treated with IL-1beta exhibited increased neuraminidase-1 and consequently increased desyalilation. IL-1beta and IFN-beta were found to be upregulated in ITP patients. IL-1beta induces the STAT2-JAK pathway, which can be blocked by baricitinib, entailing a reduced desyalilation of MK in vitro and an in-vivo resolution of ITP in mice (Zhao P et al.).

Autophagy is a physiological process that allows normal cell growth; excessive autophagy leads to increased inflammation and cell death. Abnormalities in MK autophagy have already been described, and a study by Wu J et al. found defective activity of BM macrophages, resulting in impaired MK growth and platelet production. Chaperone-mediated autophagy (an autophagy which selectively degrades chaperone-labelled cargos in lysosomes) is also impaired in ITP and could be restored with specific treatment (Xu Y et al.).

Also mesenchymal stem cell deficiency is involved in ITP pathogenesis, and this may also be due to an abnormal complement activation (Zhu X et al.).

A report by Chen Q et al. suggested a role for progesterone in influencing the gut microbiota during pregnancy in ITP, which may interfere with mesenchymal stem cell functionality.