Dangerous B-cell clones

In this issue of Blood, Wang et al1 demonstrate that the severe adverse effect vaccine-induced immune thrombotic thrombocytopenia (VITT) is caused by surprisingly structurally similar antibodies. Their findings indicate that VITT is caused by a single or only a few B-cell clones that undergo rapid clonal expansion, resulting in the production of just a few closely related antibodies. Moreover, the gene encoding the variable region of the immunoglobulin G (IgG) light chain seems to show the same polymorphism (IGLV3-21*02) in all investigated patients. Most hematologists are familiar with the role of gene polymorphisms within the human leukocyte antigen (HLA) system, predisposing to some forms of autoimmunity.2 The HLA system is important for T-cell receptor recognition of peptide-HLA complexes. In contrast, the polymorphisms in the variable regions of IgG are relevant for the structure of the antigen-binding site of IgG and the B-cell receptor.

Automated summary

In this article published in Blood, Wang et al. demonstrate that the severe adverse effect of vaccine-induced immune thrombotic thrombocytopenia (VITT) is caused by structurally similar antibodies. Their findings suggest that VITT is the result of rapid clonal expansion of a few B-cell clones, leading to the production of a few closely related antibodies. Furthermore, the gene encoding the variable region of the immunoglobulin G (IgG) light chain appears to have the same polymorphism (IGLV3-21*02) in all patients investigated.