The IgG4 Conundrum: Immunosuppressants, mRNA Vaccines, and the Risks for Kidney Transplant Recipients

In a new study published in Vaccines (2025), Ignacio Juarez of Complutense University of Madrid and team of collaborators probe a critical, unresolved issue: how immunosuppressive therapy alters the antibody response to repeated mRNA COVID-19 vaccinations in kidney transplant recipients (KTRs). Their findings unveil a striking shift in IgG subclass distribution, with a marked increase in IgG4, a non-inflammatory antibody that could signal tolerance rather than robust protection. Given the immunocompromised status of KTRs, this trend raises urgent questions about the long-term effectiveness of booster vaccinations and the unintended consequences of repeated antigen exposure.

A Deep Dive into Immune Response Alterations