Late-onset hypogammaglobulinemia after rituximab therapy

Development and implementation into practice of biologic agents has dramatically changed the approaches to the treatment of many severe diseases. But in the light of experience of their use more and more attention is paid not only to their efficacy but also to side effects. One of such medications is rituximab - a monoclonal chimeric antibody to CD20 antigen, which is expressed on the membrane of pre-B-lymphocytes and mature B-lymphocytes. In the literature more frequently are published the data about late-onset side effects of this medication, particularly hypogammaglobulinemia. The review presents the data on its prevalence after treatment of different diseases with rituximab, its severity, risk of infection. The possible mechanisms of the development of this phenomenon are discussed. Long-term hypogammaglobulinemia was shown to significantly delay the restoration of peripheral compartment of B cells, with over 90% of B cell population presented by naive B cells and significantly decreased concentration of B cells. Literature analysis demonstrates that the risk of hypogammaglobulinemia increases in multiple rituximab courses, preceding immunosuppression, decreased baseline immunoglobulin level. The need for detection of serum level of immunoglobulins before therapy with rituximab is pointed out by many authors, as the main disease can mask primary immunodeficiency, primarily common variable immunodeficiency, which requires life-term replacement therapy with intravenous immunoglobulins. The issue of administration of this therapy in secondary antibodies deficiency is not solved but severe hypogammaglobulinemia or severe infectious and inflammatory processes definitely require it. So to effectively detect hypogammaglobulinemia it is appropriate to perform monitoring of the level of immunoglobulins not only before but also during the treatment with rituximab as well as in several years after its completion.