A failure to respond to treatment or the development of resistance to therapy (through immunogenicity or other mechanisms), the use of progressively higher doses (10–30 mg/kg) with prolonged therapy windows, concomitant, and often significant systemic side-effects (infection, heart problems, malignancy) are just few of the limitations associated with the current anti-TNF biologics in the clinic (8–16). This evidence concerns the gene TNF and infection.