title: Total serum immunoglobulin levels in patients with RA after multiple B-cell depletion cycles based on rituximab: relationship with B-cell kinetics.
abstract: OBJECTIVE
  To investigate whether the incidence of secondary hypogammaglobulinaemia in patients with RA following rituximab was related to patterns of B-cell return and relapse.
  
  
  METHODS
  CD19(+) B-cell and serum immunoglobulin (sIg) determinations were done every 2 or 3 months in 137 consecutive patients treated with one or more courses of rituximab-based B-cell depletion therapy. The pattern of B-cell return, either concordant or discordant with relapse, was also recorded.
  
  
  RESULTS
  There were 119 responders. Before treatment, three patients had low IgM and four had low IgG. After the first cycle, low IgM or IgG was present in 9.2% (11/119) and 11.8% (14/119) of the patients, respectively, increasing to 38.8% (8/18) and 22.2% (4/18) after five cycles. The mean percent maximum sIg decrease/cycle was relatively constant. The CD19(+) B-cell count at repopulation was not correlated with immunoglobulin (Ig) levels after each cycle. Patients discordant for B-cell return and relapse developed significantly lower serum IgM and more low IgM episodes than concordant patients (P < 0.05).
  
  
  CONCLUSIONS
  Patients with lower baseline sIg levels tended to develop persistent IgM and IgG hypogammaglobulinaemia, resulting from an accumulation of incremental decreases after repeat cycles. This was not due to lower numbers of returning B cells in those developing low sIgs. The association of low IgM in patients with a discordant pattern of relapse suggests that underlying defects in B cells relating to survival and maturation into Ig-secreting cells, as well as attrition of IgG plasma cells may be contributing to low sIg levels in some patients.
authors.affiliation: Division of Rheumatology, Department of Medicine, University College London, Rayne Institute, 5 University Street, London WC1E 6JF, UK.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: De La Torre
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Leandro
authors.forename: Lara
authors.initials: L
authors.lastname: Valor
authors.forename: Elena
authors.initials: E
authors.lastname: Becerra
authors.forename: Jonathan C W
authors.initials: JC
authors.lastname: Edwards
authors.forename: Geraldine
authors.initials: G
authors.lastname: Cambridge
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000097:blood*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D007136:Immunoglobulins; D000069283:Rituximab