Vaccination under TNF blockade - less effective, but worthwhile

In a previous issue of Arthritis Research & Therapy, James Kobie and colleagues from the University of Rochester provide a detailed analysis of the influence of inflammation and TNF blockade on the humoral immune response to seasonal trivalent influenza vaccines [1]. Their 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 first became clear that TNF is essential for fighting 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]. The 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. The inflammatory removal of cells damaged in this way may be impaired under TNF blockade.The 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 effects of seasonal influenza 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 influenza antigens were measured in a large group of 164 patients with rheumatoid arthritis (RA), including 61 under TNF blockade and 70 under methotrexate, and in 97 healthy in