Immunogenicity is just one of the many benefits of our immune system and is defined as the ability of different substances to trigger an adaptive cellular and humoral cell immune response that is longterm and leads to immunological memory. In rheumatology and other medical specialties such as dermatology, gastroenterology, neurology and immunology, biological proteins derived from biotechnology are increasingly used as therapeutic agents. These proteins, like many other exogenous agents can induce humoral and cellular immune responses. However, in recent years we have noticed how these concepts have been interpreted haphazardly, and sometimes in the wrong way from the point of view of their clinical significance. The immune response or immunogenicity which can be triggered by a therapeutic protein has been proposed as a cause of potential clinical events, including hypersensitivity reactions, decreased effectiveness of the therapeutic molecule and induction of immune processes, including the formation of antibodies against the protein in question.1,2 The most dreaded immunogenicity in clinical terms occurs due to the so-called neutralizing anti-drug antibodies which, as their name implies, have the ability to bind the agent (drug) and neutralize it, preventing its biological or therapeutic function.3 Many factors can influence the immunogenicity of therapeutic proteins, including those inherent to the patient, the disease itself or those related to the product itself. The determinants of patient-related immunogenicity that may predispose unwanted immune responses include the underlying disease, genetic factors and baseline immune status, including associated immunomodulatory therapy. Furthermore, product related factors also influence the probability of inducing an immune response; for example, the route of administration, the type of protein, aspects of the manufacturing process, impurity profile or excipients and formulation characteristics, stability, degradation products or aggregates, dosage, the dosing interval and treatment duration.4–6 The immune response mechanism directed against therapeutic biological molecules seems to be due to “transient” loss of