Characterization of reverse-engineered anti-PF4 stereotypic antibodies derived from serum of patients with VITT

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a complex multifactorial medical condition observed rarely following vaccination with adenovirus-based coronavirus disease 2019 (COVID-19) vaccines, [1][2][3][4][5][6] and also after other types of vaccines.[7][8][9] VITT involves platelet factor 4 (PF4) autoimmunity, which is also observed in heparin-induced thrombocytopenia.[10][11][12] However, it is now known that VITT and heparininduced thrombocytopenia antibodies bind separate epitopes on PF4 and have distinct clonal profiles.[13][14][15] We recently discovered highly stereotypic anti-PF4 antibodies in 5 patients with VITT after ChAdOx1 nCoV-19 vaccination using mass spectrometry-based proteomics.These unique serum clonotypes are specified by identical IGLV3-21*02 allelic light chains paired with heavy chains expressing shared heavy chain third complementarity-determining region (HCDR)3 amino acids motifs.These findings shed light on the mechanisms of this dangerous adverse reaction and may contribute to understanding how these pathogenic autoantibodies are induced.