title: Rituximab and immune deficiency: case series and review of the literature.
abstract: BACKGROUND
  As the indications and use of rituximab continue to expand, the reports of long-term effects of anti-CD20--mediated B-cell depletion on the immune system accumulate.
  
  
  OBJECTIVE
  We report a group of patients with immunodeficiency who were treated with rituximab and present their immunologic data.
  
  
  METHODS
  A retrospective chart review identified patients with immunodeficiency who received rituximab for treatment of their primary disease and required immunoglobulin replacement therapy (IGRT). Pre-IGRT immunoglobulins, specific antibodies, B-cells, and B-cell phenotype were recorded and analyzed.
  
  
  RESULTS
  We identified 11 patients with immunodeficiency who received rituximab and required IGRT. Two of these patients were diagnosed with common variable immunodeficiency before rituximab treatment. Nine other patients had hypogammaglobulinemia and did not achieve an adequate response to polysaccharide vaccine. There was a significant delay in B-cell recovery. B-cell phenotypes identified predominantly naive B cells in the blood of these patients with significant decrease in switched and memory B cells.
  
  
  CONCLUSIONS
  There are patients with persistent B-cell dysfunction long after rituximab treatment was discontinued. Some of these patients required IGRT. These patients should be distinguished from patients with primary immunodeficiency diseases. Routine baseline B-cell numbers and serum immunoglobulin levels before starting immunomodulatory therapy are required to help distinguish primary immunodeficiency diseases from secondary rituximab-induced, transient, and, at times, prolonged immune suppression. Periodic monitoring is prudent to identify immune recovery. Post-rituximab B-cell phenotyping may help identify the patients who will develop persistent immune dysfunction caused by an unidentified underlying disease or the prolonged effect of rituximab treatment.
authors.affiliation: Division of Allergy, Asthma and Immunology, North Shore-LIJ Health System, Great Neck, NY; Hofstra-North Shore-LIJ School of Medicine, Hempstead, NY; Long Island Jewish Medical Center, New Hyde Park, NY. Electronic address: bkaplan@nshs.edu.
authors.forename: Blanka
authors.initials: B
authors.lastname: Kaplan
authors.affiliation: Division of Allergy, Asthma and Immunology, North Shore-LIJ Health System, Great Neck, NY.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Kopyltsova
authors.affiliation: Hofstra-North Shore-LIJ School of Medicine, Hempstead, NY; Long Island Jewish Medical Center, New Hyde Park, NY.
authors.forename: Amrita
authors.initials: A
authors.lastname: Khokhar
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, NY.
authors.forename: Fung
authors.initials: F
authors.lastname: Lam
authors.affiliation: Division of Allergy, Asthma and Immunology, North Shore-LIJ Health System, Great Neck, NY; Hofstra-North Shore-LIJ School of Medicine, Hempstead, NY; Long Island Jewish Medical Center, New Hyde Park, NY; Feinstein Institute for Medical Research, Manhasset, NY.
authors.forename: Vincent
authors.initials: V
authors.lastname: Bonagura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002675:Child, Preschool; D006801:Humans; D007136:Immunoglobulins / Q000097:blood / Q000627:therapeutic use; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D007155:Immunologic Factors / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008875:Middle Aged; D000069283:Rituximab; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007136:Immunoglobulins; D007155:Immunologic Factors; D000069283:Rituximab
keywords: B-cell phenotype; Hypogammaglobulinemia; IGRT; Immunodeficiency; Immunoglobulin replacement therapy; PITID; Persistent immunodeficiency after treatment with immunomodulatory drug; Rituximab