Page 203 - Haematologica Vol. 107 - September 2022

ARTICLE - ITP antibody predicts desialylation and apoptosis S.S. Zheng et al.
anti-GPIIb/IIIa antibody-driven ITP,36,37 we further examined the relationship between platelet FcγR and the down- stream signaling of these ITP antibodies in platelet apop- tosis. FcγRIIa inhibitor IV.3 effectively suppressed antibody-induced platelet loss of ΔΨm, indicating that anti-GPIIb/IIIa antibodies may signal through FcγR to initi- ate platelet apoptosis.
In addition to the ability to predict desialylation and apop- tosis, antibody specificity appears to have an impact on the predominant thrombocytopenic mechanism in ITP. Unlike a prior report,28 we found that anti-GPIIb/IIIa anti- bodies resulted in higher degree of NEU1 translocation. On the other hand, anti-GPIb/IX antibodies appeared to cause more platelet apoptosis. A recent systematic study exam- ined antibody specificity and platelet/megakaryocyte de- sialylation.36 The report described no association between antibody-induced desialylation and platelet apoptosis in
ITP.36 However, this study did not report the relationship between antibody specificity and the induction of either desialylation or apoptosis. In our study, the finding of dif- ferential effects with respect to the antibody specificity provides a potential new dimension to the understanding of ITP pathogenesis.
The small number of patients containing sole anti-GPV antibodies precludes definite conclusions on its effect on the subsequent platelet events, but it is notable that sera from both patients did not induce desialylation. Interest- ingly, this result is consistent with the finding by Amini and colleagues, who recently reported the lack of hepatic uptake of Indium-111 labeled platelet in patients with anti- GPV antibodies.49 Of note, serum from one anti-GPV posi- tive patient induced significant loss of platelet ΔΨm, indicating anti-GPV may drive ITP via platelet apoptosis. While APA testing is available in specialized platelet lab-
AB
Figure 5. Effect of anti-GPV antibodies on platelet desialylation and apoptosis. (A) Effect on desialytion and (B) on apoptosis. CTRL: control; Pt: patient. Data shown as mean ± standard deviation. ns: non-significant, ***P<0.001. Kruskal-Wallis test with Dunn’s multiple comparison. MFI: mean fluorescence intensity.
Figure 6. Murine model of immune thrombocytopenia with anti-GPIIb/IIIa antibodies. Effect of 3 immune thrombocytopenia (ITP) patients’ (Pt) immunoglobulin G (IgG) (black dots) and oseltamivir treatment (red dots) in the presence of patient IgG, on human platelet (plt) survival in NOD/SCID mice (n=5 for each patient group) measured as human platelet percentage at 2, 4, and 6 hours after IgG injection. Data shown as mean ± standard error of the mean. Levels of significance are expressed as P-values. ns: non- significant, **P<0.01, ****P<0.0001. Linear mixed model. NOD/SCID: non-obese diabetic/severe combined immunodeficient.
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