Platelet desialylation correlates with efficacy of first-line therapies for immune thrombocytopenia.
Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder. Despite considerable investigation, the pathogenesis of ITP remains incompletely understood, and for many patients, effective therapy is still unavailable. Using murine models and in vitro studies of human blood samples, we recently identified a novel Fc-independent platelet clearance pathway, whereby antibody-mediated desialylated platelets can be cleared in the liver via asialoglycoprotein receptors, leading to decreased response to standard first-line therapies targeting Fc-dependent platelet clearance. Here, we evaluated the significance of this finding in 61 ITP patients through correlation of levels of platelet desialylation with the efficacy of first-line therapies. We found that desialylation levels between different responses to treatment groups were statistically significant (p < 0.01). Importantly, correlation analysis indicated response to treatment and platelet desialylation were related (p < 0.01), whereby non-responders had significantly higher levels of platelet desialylation. Interestingly, we also found secondary ITP and certain non-ITP thrombocytopenias also exhibited significant platelet desialylation compared to healthy controls. These findings designate platelet desialylation as an important biomarker in determining response to standard treatment for ITP. Furthermore, we show for the first time platelet desialylation in other non-ITP thrombocytopenias, which may have important clinical implications and deserve further investigation.
Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.|The Hematological Research Center of Anhui Medical University, Hefei, 230601, China.
Lili
L
Tao
Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Qingshu
Q
Zeng
Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science and Department of Laboratory Medicine of St. Michael's Hospital, Toronto, Canada.|Canadian Blood Services, Ottawa, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
June
J
Li
Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science and Department of Laboratory Medicine of St. Michael's Hospital, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Miao
M
Xu
Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.|The Hematological Research Center of Anhui Medical University, Hefei, 230601, China.
Jiajia
J
Wang
Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.|The Hematological Research Center of Anhui Medical University, Hefei, 230601, China.
Ying
Y
Pan
Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.|The Hematological Research Center of Anhui Medical University, Hefei, 230601, China.
Huiping
H
Wang
Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.|The Hematological Research Center of Anhui Medical University, Hefei, 230601, China.
Qianshan
Q
Tao
Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Yang
Y
Chen
Department of Hematology and Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China.
Jun
J
Peng
Department of Hematology and Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China.
Ming
M
Hou
Department of Hematology, Erasmus MC, Rotterdam, The Netherlands.|Department of Plasmaproteins Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands.
Arend Jan Gerard
AJ
Jansen
Toronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science and Department of Laboratory Medicine of St. Michael's Hospital, Toronto, Canada. nih@smh.ca.|Canadian Blood Services, Ottawa, Canada. nih@smh.ca.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. nih@smh.ca.|Department of Physiology, and Department of Medicine, University of Toronto, Toronto, Canada. nih@smh.ca.
Heyu
H
Ni
Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China. zzzm889@163.com.|The Hematological Research Center of Anhui Medical University, Hefei, 230601, China. zzzm889@163.com.
Zhimin
Z
Zhai
D000328:Adult; D000818:Animals; D000906:Antibodies / Q000276:immunology; D037263:Asialoglycoprotein Receptor / Q000276:immunology; D001212:Asialoglycoproteins / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009844:Oligosaccharides / Q000276:immunology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000175:diagnosis*; D012074:Remission Induction; D016896:Treatment Outcome
D000906:Antibodies; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D009844:Oligosaccharides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor; C025469:asialooligosaccharides
Antibody; Desialylation; Immune thrombocytopenia; Platelet; Steroid and IVIG therapy