Abstract Number: PB1851
Meeting: ISTH 2020 Congress
Background: Cancer patients are at high risk of developing venous thromboembolism leading to high rates of mortality. The reason might be the elevation of procoagulant proteins and down regulation of natural anti-coagulants like antithrombin (AT). The AT modulates both coagulation and angiogenesis. During respiratory burst hypochlorous acid (HOCl) is generated in vivo which may cause alteration in various biomolecules like proteins and DNA. Structural alteration in proteins may lead to autoantibodies generation in vivo. Therefore, it is a thought of interest to investigate the role of HOCl in cancer.
Aims: To see the role of HOCl-modified AT in cancer.
Methods: The purified AT was modified with various concentrations of HOCl to asses structural and functional alterations by various physicochemical techniques and enzymatic assays. Sera of pre-treated cancer patients (N=60) with mean age of 40±25 were collected. Sera from healthy subjects (N=30) served as negative control. Statistical study was done with the results obtained. This study had clearance from bioethical committee.
Results: HOCl induced secondary and tertiary structural changes in AT were observed by various techniques like absorbance and fluorescence spectroscopy, and Far-UV CD. While, the HOCl-modified native-AT showed fragmentation and polymerisation (further conformed by TEM), cleaved and latent conformers exhibited fragmentation only on PAGE. HOCl reduced the catalytic activity of AT as assessed by factor Xa and thrombin inhibition assays. Compared to the unmodified AT, the HOCl-modified counterparts were more specifically recognised by cancer autoantibodies as assessed by direct binding and competition ELISA, showing probable role of HOCl-modified AT in cancer.
Conclusions: We propose that in vivo generated HOCl, during respiratory burst, may cause structural alteration in AT and hence, generation of neo-epitopes on it. Also functional loss in AT points towards a shift in more prothrombotic and proangiogenic environment.
To cite this abstract in AMA style:Ahmad P, Tantry IQ, Ali A, Siddiqui SA, Rehman SU, Waris S, Ahmad I, Jairajpuri MA. Hypochlorous Acid Modification to Antithrombin Results in Generation of Neo-epitopes, and a Shift towards Prothrombotic and Proangiogenic State in Cancer Patients [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/hypochlorous-acid-modification-to-antithrombin-results-in-generation-of-neo-epitopes-and-a-shift-towards-prothrombotic-and-proangiogenic-state-in-cancer-patients/. Accessed November 30, 2021.
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