According to various evidences, the main risk factors for opportunistic infections are advanced age (OR 3.0 for patients>50 years) (199) and the simultaneous use of multiple immunosuppressive drugs, since the transition from a single immunomodulator to combination therapy increases the relative risk of infections from 2.9 to 14.5 (200) Considering TNF-α inhibitors alone – which are in themselves sufficient to define high-level immunosuppression, as previously mentioned – the TREAT registry showed an increased risk of serious infections with these drugs (HR 1.47) (201). This evidence concerns the gene TNF and infection.