Baseline serum immunoglobulin levels in patients with rheumatoid arthritis: relationships with clinical parameters and with B-cell dynamics following rituximab

Introduction To investigate whether levels of serum immunoglobulins (slgs) 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, I, 3 and 5 months) in 112 patients with RA after I cycle of RTX were included. All showed adequate B-cell depletion (<5 CD19+B cells/mu l) after I month. Normal slg ranges were for IgA (0.7-4.0 gIL), IgG (7.0-16.0 gIL), and IgM (0.4-2.3 gIL). Results Baseline IgA levels were raised in 29 patients, IgG in 18 and IgM in II. 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 (5118) 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 slgs within normal limits. Conclusions sIgA levels in RA patients remained raised in a higher proportion of patients than other slg 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.