Vaccination under TNF blockade - less effective, but worthwhile

Kobie and colleagues from the University of Rochester provide a detailed analysis of the infl uence of infl am ma-tion and TNF blockade on the humoral immune response to seasonal trivalent infl uenza vaccines [1]. Th eir manuscript sheds light on the role of TNF in B and plasma cell function, and gives a partial answer to the important clinical questions of how to handle vaccinations of patients under TNF blockade. When TNF blockers became available, it fi rst became clear that TNF is essential for fi ghting intracellular pathogens , such as Mycobacterium tuberculosis or Listeria monocytogenes. In contrast, and despite the cytokine's name, TNF blockade has not been shown to play a role in solid tumor formation in general [2]. Th e two notable exceptions are skin cancers [2] and, in the Wegener's Granulomatosis Etanercept Trial [3], combination therapy with cyclophosphamide and etanercept. Under both conditions, one would expect DNA strand breaks to be newly induced by UV light and cyclophosphamide, respectively. Th e infl ammatory removal of cells damaged in this way may be impaired under TNF blockade. Th e fact that, under TNF blockade, many patients develop anti-nuclear antibodies, antibodies to double-stranded DNA, or antibodies to phospholipids [4,5] has been seen as an argument that blocking TNF fostered the humoral immune response, which chronic TNF exposure would otherwise keep in check [5,6]. Kobie and colleagues [1] now, in a combination of approaches to analyze the eff ects of seasonal infl uenza vaccination, back data that the contrary is true, at least for the normal, protective humoral response, in that TNF apparently leads to increased antibody titers [1]. By hemagglutination inhibition assay, pre-and post-vaccination antibody titers to infl uenza antigens were measured in a large group of 164 patients with rheu-matoid arthritis (RA), including 61 under TNF blockade and 70 under methotrexate, and in 97 healthy individuals. While patients treated with TNF blockers, mostly in combination with methotrexate, depending on the exact antigen, reached only approximately half of the normal antibody levels one month after the vaccination, this eff ect persisted at six months. Th e eff ect of methotrexate was similar, but much milder, while untreated RA eff ectively increased the immune response compared to healthy individuals. Th e authors argued that TNF blockade would likely aff ect memory B cells, given that infl uenza vaccine responses mostly are secondary immune responses. One month after vaccination, …