Suppressed IgG4 class switching in dupilumab‐ and TNF inhibitor‐treated patients after mRNA vaccination

• DOI: 10.1111/all.16089
• Publication Date: 2024-03-05T06:13:35Z
• Authors: Anika M. Valk; Jim B. D. Keijser; Koos P. J. van Dam; Eileen W. Stalman; Luuk Wieske; Maurice Steenhuis; Laura Y. L. Kummer; Phyllis I. Spuls; Marcel W. Bekkenk; Annelie H. Musters; Nicoline F. Post; Angela L. Bosma; Barbara Horváth; Dirk‐Jan Hijnen; Corine R. G. Schr...; Zoé L. E. van Kempen; Joep Killestein; Adriaan G. Volkers; Sander W. Tas; Laura Boekel; Gerrit J. Wolbink; Sofie Keijzer; Ninotska I. L. De...; Melanie van Deelen; Gerard van Mierlo; Taco W. Kuijpers; Filip Eftimov; S. Marieke van Ham; Anja ten Brinke; Theo Rispens
• Keywords: Dupilumab

Abstract Background The noninflammatory immunoglobulin G4 (IgG4) is linked to tolerance and unique humans. Although poorly understood, prolonged antigenic stimulation IL‐4‐signaling along the T helper 2‐axis may be instrumental in IgG4 class switching. Recently, repeated SARS‐CoV‐2 mRNA vaccination has been skewing. widely used immunosuppressive drugs have shown only moderately affect humoral responses vaccination, effect on switching not investigated. Methods Here we study impact of such drugs, including IL‐4 receptor‐blocking antibody dupilumab, skewing upon vaccination. Receptor‐binding domain (RBD) specific were longitudinally measured 600 individuals, patients with immune‐mediated inflammatory diseases treated a TNF inhibitor (TNFi) and/or methotrexate (MTX), healthy/untreated controls, after Results We observed substantial increase proportion RBD‐specific antibodies (median 21%) controls third This was profoundly reduced dupilumab‐treated (<1%). Unexpectedly, an equally strong suppression TNFi‐treated (<1%), whereas MTX caused modest reduction (7%). total IgG levels hardly affected by these drugs. Minimal observed, when primary adenoviral vector‐based. Conclusions Our results imply critical role for IL‐4/IL‐13 as well vivo These novel findings advance our understanding switch dynamics, benefit induction strategies, treatment pathologies vaccine optimization.