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

TO THE EDITOR:

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,^1-6 and also after other types of vaccines.^7-9 VITT involves platelet factor 4 (PF4) autoimmunity, which is also observed in heparin-induced thrombocytopenia.^10-12 However, it is now known that VITT and heparin-induced thrombocytopenia antibodies bind separate epitopes on PF4 and have distinct clonal profiles.^13-15 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...