title: Baseline serum immunoglobulin levels in patients with rheumatoid arthritis: relationships with clinical parameters and with B-cell dynamics following rituximab.
abstract: OBJECTIVE
  To investigate whether levels of serum immunoglobulins (sIgs) at baseline were associated with clinical parameters or B-cell dynamics following rituximab (RTX) in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Baseline Ig levels, C-reactive protein (CRP), DAS28 and CD19+ve B-cell count (baseline, 1, 3 and 5 months) in 112 patients with RA after 1 cycle of RTX were included. All showed adequate B-cell depletion (<5 CD19+B cells/μl) after 1 month. Normal sIg ranges were for IgA (0.7-4.0 g/L), IgG (7.0-16.0 g/L), and IgM (0.4-2.3 g/L).
  
  
  RESULTS
  Baseline IgA levels were raised in 29 patients, IgG in 18 and IgM in 11. CRP levels were significantly higher in patients with raised IgA and IgG compared to patients with normal levels (p=0.0002; p=0.03). At nadir after RTX, median levels of all sIgs decreased significantly although 16 patients (55%) remained with raised IgA, 28% IgG (5/18) and 27% IgM (3/11). Patients with raised IgA had higher minimum levels reached of CRP and of DAS28 (p=0.002; p=05). After 5 months, a higher percentage of patients with raised baseline sIgA had repopulated and were found to have shorter clinical responses than those with sIgs within normal limits.
  
  
  CONCLUSIONS
  sIgA levels in RA patients remained raised in a higher proportion of patients than other sIg after RTX. Raised sIgA was associated with a less robust clinical response to RTX and with B-cell repopulation coincident with relapse. Expanded or more permissive microenvironments for long-lived IgA plasma cells may be related to the presence of disease more refractive to B-cell depletion therapy.
authors.affiliation: Centre for Rheumatology, University College of London, London, UK. inma.torre.ortega@googlemail.com
authors.forename: Inmaculada
authors.initials: I
authors.lastname: de la Torre
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Leandro
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*; D018941:Antigens, CD19 / Q000378:metabolism; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007136:Immunoglobulins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D000069283:Rituximab; D055502:Secondary Prevention
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D018501:Antirheumatic Agents; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D000069283:Rituximab; D002097:C-Reactive Protein