{Reference Type}: Journal Article
{Title}: Anti-TNF therapy impairs both short- and long-term IgG responses after repeated vaccination.
{Author}: Buhre JS;Pongracz T;Geisen UM;Schubert M;Wang W;Nouta J;Obara M;Lehrian S;Rahmöller J;Petry J;Tran F;Schreiber S;Sümbül M;Berner D;Gerdes S;Schirmer J;Longardt AC;Hoff P;Kalinke U;Ludwig RJ;Bartsch YC;Hoyer BF;Wuhrer M;Ehlers M;
{Journal}: Allergy
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jul 25
{Factor}: 14.71
{DOI}: 10.1111/all.16241
{Abstract}: <B>BACKGROUND: </B>Recently, it has been questioned whether vaccination of patients with inflammatory (auto)immune diseases under anti-tumor necrosis factor (TNF) treatment leads to impaired vaccine-induced immune responses and protection against breakthrough infections. However, the effects of TNF blockade on short- and long-term immune responses after repeated vaccination remain unclear. Vaccination studies have shown that initial short-term IgG antibodies (Abs) carry highly galactosylated and sialylated Fc glycans, whilst long-term IgG Abs have low levels of galactosylation and sialylation and are most likely generated by long-lived plasma cells (PCs) derived primarily from the germinal center (GC) response. Thus, IgG Fc glycosylation patterns may be applicable to distinguish short- and long-term vaccine responses after repeated vaccination under the influence of anti-TNF treatment.<BR><B>METHODS: </B>We used COVID-19 vaccination as a model to investigate vaccine-induced IgG subclass levels and Fc glycosylation patterns, B cell subsets, and effector functions of short- and long-term Ab responses after up to three vaccinations in patients on anti-TNF or other immunosuppressive treatments and in healthy individuals. Using TriNetX, a global healthcare database, we determined the risk of SARS-CoV-2 breakthrough infections in vaccinated patients treated with anti-TNF or other immunosuppressive drugs.<BR><B>RESULTS: </B>Anti-TNF treatment reduced the long-term abundance of all anti-S IgG subclasses with low levels of galactosylation and sialylation. Re-activation of potential memory B cells initially generated highly galactosylated and sialylated IgG antibodies, which were progressively reduced after each booster dose in anti-TNF-treated patients, especially in the elderly. The reduced short- and long-term IgG (1) levels in anti-TNF-treated patients correlated with diminished functional activity and an increased risk for the development of COVID-19.<BR><B>CONCLUSIONS: </B>The data suggest that anti-TNF treatment reduces both GC-dependent long-lived PCs and GC-dependent memory B cell-derived short-lived PCs, hence both the long- and short-term IgG subclass responses, respectively, after repeated vaccination. We propose that anti-TNF therapy, especially in the elderly, reduces the benefit of booster vaccination.