Abstract Number: PB0817
Meeting: ISTH 2021 Congress
Background: Immune thrombocytopenia (ITP) is an autoimmune disease that can cause severe bleeding symptoms and it can occur in both pediatric and adult patients. Antiplatelets antibodies, T-cell mediated destruction of platelets and impaired megakaryopoiesis leading to a reduced platelet formation by loss of autophagy have been described as possible etiologies of the low platelet counts that hallmark this disorder. We have previously reported an increased phosphatidylserine exposure and caspase-3 in platelets from acute ITP patients, suggesting that platelet apoptosis is involved into the ITP pathogenesis.
Aims: In our present study, we aimed to identify ITP platelets’ clearance mechanisms that control the interplay between the apoptotic and autophagic machinery.
Methods: We performed an apoptosis proteomic profiling of 35 genes (R&D Systems) and we validated our results by RT-qPCR and immunoblotting.
Results: We could demonstrate by apoptosis proteomic profiling significantly increased expression levels of some apoptotic genes such as clusterin (CLU), pro-caspase 3, catalase, TRAILR1/DR4, Bax, Bad and Bcl-2 compared to healthy controls in platelet-rich plasma (PRP) from 10 ITP patients. We could validate by both RT-qPCR and immunoblotting that CLU, a stress-activated chaperone, is significantly increased in both acute and chronic ITP. Further, we investigated specific autophagy and ER-autophagy markers by Western blot and RT-qPCR. We could observe that the mRNA expression of autophagy-initiation (Beclin-1), -autophagosome (p62) and -lysosome (LAMP1) markers was up to 3-fold significantly increased in acute and chronic ITP patients. mRNA levels of ER-autophagy genes CLIMP63 and FAM134b were significantly increased whereas ATL3 and REEP4 showed significantly decreased levels.
Conclusions: Our results indicate an impairment in the modulation of apoptosis and autophagy pathways in ITP platelets. We assume that targeting apoptosis and/or autophagy pathway genes could lead to potential identification of new biomarkers and therapies against this autoimmune disorder, and thereby, could it provide an augmented quality of life of ITP patients.
To cite this abstract in AMA style:Stein T, Hinselmann R, Gowin C, Greber D, Shllaku S, Gölz N, Schmugge M, Franzoso FD. Platelet Apoptosis and Autophagy in Pediatric Immune Thrombocytopenia: New Mechanistic Insights [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/platelet-apoptosis-and-autophagy-in-pediatric-immune-thrombocytopenia-new-mechanistic-insights/. Accessed December 6, 2023.
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