Differentiating pathogenic from bystander autoantibodies in immune thrombocytopenia using intact glycoproteindeficient megakaryocytes. Haematologica 2026 May 01;111(5):1725-1734
Date
12/11/2025Pubmed ID
41376564Pubmed Central ID
PMC13136829DOI
10.3324/haematol.2025.288832Scopus ID
2-s2.0-105038109812 (requires institutional sign-in at Scopus site)Abstract
Autoantibodies targeting platelet surface glycoproteins (GP) are the primary cause of immune thrombocytopenia (ITP), however testing for these autoantibodies is not routinely employed mainly because current diagnostic tests lack sufficient sensitivity. To overcome this and other diagnostic limitations, we generated HLA class I-negative, blood group O, induced pluripotent stem cell lines, and gene-edited them to produce a novel panel of GP-deficient, in vitro-derived megakaryocytes (MK). Using GPIIb-, GPIbα- and GPIX-deficient MK allowed sensitive and specific identification and characterization of both GPIIb-IIIa- and GPIb/IX-specific plasma autoantibodies, as well as rare, previously undescribed patient autoantibodies targeting GPIX. The availability of frozen bioengineered MK expressing select platelet GP antigens on their surface simplifies the detection of anti-platelet autoantibodies involved in disease progression, while avoiding detection of non-pathogenic bystander autoantibodies that are sometimes generated by secondary exposure to "cryptic epitopes", and that can otherwise confound diagnosis and treatment. Use of intact MK selectively deficient in the GP that comprise the major targets of platelet autoantibodies has the potential to significantly improve clinical diagnosis and treatment of ITP.
Author List
Zhang N, Uzun G, Bakchoul T, Curtis BR, Newman PJAuthor
Brian Curtis PhD Director in the Platelet & Neutrophil Immunology Laboratory department at BloodCenter of WisconsinMESH terms used to index this publication - Major topics in bold
AutoantibodiesHumans
Induced Pluripotent Stem Cells
Megakaryocytes
Platelet Glycoprotein GPIb-IX Complex
Platelet Membrane Glycoproteins
Purpura, Thrombocytopenic, Idiopathic
