Page 204 - Haematologica Vol. 107 - September 2022

ARTICLE - ITP antibody predicts desialylation and apoptosis S.S. Zheng et al.
oratories, routine testing has not been recommended, and ITP remains a disease without any confirmatory investi- gation or a “gold standard” test. Given the additional im- portant information provided by a positive result, which is the ability of patients’ antibodies to induce platelet de- sialylation and apoptosis, we suggest ITP antibody testing to be incorporated into ITP management algorithm. It may provide new insight into ITP pathology and could guide treatment individualization.
The main weakness of our study is that it was performed on stored patient samples. Prospective evaluation of path- ological ITP sera would allow us to correlate the sera’s ability to induce desialylation and apoptosis with patients’ treatment and disease response. Another significant limi- tation in using stored samples is the lack of direct testing on patient platelets. Direct glycoprotein-specific APA as- says will improve testing sensitivity43,50 and is the recom- mended test by the International Society of Thrombosis and Hemostasis (ISTH).51 Nevertheless, indirect examin- ation allowed us to determine the impact of APA present in the patient serum on donor platelets and compared such effect of different patient samples as well as with controls.
Another limitation is the small number of patients with single APA specificity. Larger sample size is desirable to capture the difference between each antibody type and the associated downstream effect on platelet survival more accurately, which may ultimately lead to ITP treat- ment individualization. An additional challenge is the dif- ficulties in performing platelet antibody testing outside specialized laboratories. In agreement with the ISTH rec- ommendation, we recommend referral of platelet immu- nology tests to a centralized laboratory, where staff are adequately trained in specialized methods to minimize laboratory variability.51
In conclusion, we report the predictive capability of APA in relation to the potential underlying ITP mechanisms, specifically platelet desialylation and apoptosis. We showed the differential effects of antibody subtypes on these two ITP pathogenesis pathways and the role of FcγR on anti-GPIIb/IIIa antibodies induced platelet apoptosis.
References
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We also demonstrated the therapeutic effect of neur- aminidase inhibitor in platelet preservation despite the presence of anti-GPIIb/IIIa antibodies. Hence, such treat- ment can potentially be applied to most ITP patients since it is likely that both anti-GPIIb/IIIa antibodies (this study) and anti-GPIb/IX antibodies28 lead to platelet desialylation. Further collaboration is required to investigate the treat- ment potential using neuraminidase and/or apoptosis in- hibitors in prospective randomized ITP clinical trials.
Disclosures
No conflicts of interest to disclose.
Contributions
SSZ designed and performed experiments, collected, and analyzed the data, and wrote the manuscript; ZA, HHLL, RW, FY performed the experiments; JSP and BHC con- tributed equally, provided project supervision, and reviewed the manuscript. All authors read and approved the manu- script.
Acknowledgements
The authors thank Dr. Zhixin Liu (Stats Central, UNSW) for her statistical expertise.
Funding
This work was supported by the National Health and Medi- cal Research Council project grant to BHC (GNT 1012409) as well as St. George and Sutherland Medical Research Foundation Grant to JSP. SSZ received NSW Ministry of Health PhD Scholarship. In Vivo data presented in this work was acquired at the Mark Wainright Analytical Centre (MWAC) of UNSW Sydney, which is in part funded by the Re- search Infrastructure Program of UNSW.
Data-sharing statement
Data that support the findings of this study are available from the corresponding author upon reasonable request. All data generated or analysed are included in this pub- lished article.
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