title: Suppression of normal immune responses after treatment with rituximab.
abstract: OBJECTIVE
  Because rituximab is increasingly used in systemic autoimmune diseases, alone or in combination with other immunosuppressive medication, secondary reduction of normal immune defenses has become a more significant clinical problem.
  
  
  RESULTS
  The goal of rituximab treatment of immune-mediated conditions is complete depletion of circulating B cells. Studies have suggested that lack of complete B-cell depletion is associated with nonresponse, and B-cell repletion can predict relapse. The resulting prolonged B-cell depletion is associated with risk of adverse effects including hypogammaglobulinemia, increased risk of infection, failure to develop immune responses after vaccination, and neutropenia. Pre-existing hypogammaglobulinemia has been linked to increased risk of reduction of IgG levels and serious infections after rituximab therapy, and concomitant cyclophosphamide therapy has been associated with an increased risk of developing hypogammaglobulinemia.
  
  
  CONCLUSIONS
  Although rituximab therapy is effective in the treatment of many systemic autoimmune diseases and has an acceptable safety profile, treating physicians need to keep in mind that pre-existing hypogammaglobulinemia and likely also use of additional immunosuppressive agents can increase the risk of prolonged hypogammaglobulinemia and infection. In keeping with current recommendations for rheumatoid arthritis, we recommend that all patients who undergo rituximab therapy have baseline IgG, IgM, and IgA measurements and also have immunoglobulin levels monitored periodically during treatment.
authors.affiliation: aDepartment of Internal Medicine, Division of RheumatologybDepartment of Internal Medicine and of Pediatrics and Communicable Diseases, Division of Allergy and ImmunologyAnn Arbor, Michigan, USA.
authors.forename: Ruba
authors.initials: R
authors.lastname: Kado
authors.forename: Georgiana
authors.initials: G
authors.lastname: Sanders
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: McCune
mesh_terms: D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D012008:Recurrence; D000069283:Rituximab / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D000069283:Rituximab