Chronic alcoholism should be considered as a cause of increased total serum IgE, regardless of the severity of the underlying liver disease.

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.

Serum levels of B cell-activating factor (BAFF) rise following rituximab (RTX) therapy in patients with rheumatoid arthritis (RA). Initiation of naive B cell return to the periphery and autoreactive B cell expansion leading to relapse after RTX may therefore be linked to interactions between BAFF and BAFF-binding receptors (BBR). Relationships between serum BAFF and BBR expression [(BAFFR, calcium signal modulating cyclophilic ligand interactor (TACI) and B cell maturation antigen (BCMA)] were determined on B cell subsets, defined using immunoglobulin (Ig)D/CD38. Twenty pre-RTX and 18 RA patients relapsing after B cell depletion were included. Results were analysed with respect to timing of relapse up to 7 months after peripheral B cell return (≥ 5 B cells/μl) and to serum BAFF levels. After B cell return, B cell populations from relapsing patients had significantly lower BAFFR expression compared to HC and pre-RTX patients. The percentage of BAFFR B cells increased with time after B cell return and was correlated inversely with serum BAFF levels. BAFFR expression remained reduced. The percentage of TACI memory B cells were lower in RA patients after RTX compared with healthy controls (HC). BCMA expression (% and expression) did not differ between patients and HC. Relapse following B cell return appeared largely independent of the percentage of BAFFR or percentage of BCMA B cells or serum BAFF levels. The lower percentage of TACI memory B cells may reduce inhibitory signalling for B cell differentiation. In patients relapsing at longer periods after B cell return, recovery of the B cell pool was more complete, suggesting that selection or expansion of autoreactive B cells may be needed to precipitate relapse.

SummaryAutoantibodies inhibiting the activity of the metalloproteinase, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), underlie the pathogenesis of thrombotic thrombocytopenic purpura (TTP). Rituximab (RTX) combined with plasma-exchange (PEX) is an effective treatment in TTP. Patients can remain in remission for extended periods following PEX/RTX, and this is associated with continuing reduction in antibodies to ADAMTS13. Factors controlling B cell differentiation to autoantibody production, including stimulation through the B cell receptor and interactions with the B cell-activating factor (BAFF), may thus impact length of remission. In this cross-sectional study, we measured naive and memory B cell phenotypes [using CD19/immunoglobulin (Ig)D/CD27] following PEX/RTX treatment in TTP patients at B cell return (n = 6) and in 12 patients in remission 10-68 months post-RTX. We also investigated relationships among serum BAFF, soluble CD23 (sCD23 -a surrogate measure of acquiring B memory (CD27 + ) phenotype) and BAFF receptor (BAFF-R) expression. At B cell return after PEX/RTX, naive B cells predominated and BAFF-R expression was reduced compared to healthy controls (P < 0·001). In the remission group, despite numbers of CD19 + B cells within normal limits in most patients, the percentage and absolute numbers of pre-switch and memory B cells remained low, with sCD23 levels at the lower end of the normal range. BAFF levels were correlated inversely with BAFF-R expression and time after therapy. In conclusion, the long-term effects of RTX therapy in patients with TTP included slow regeneration of memory B cell subsets and persistently reduced BAFF-R expression across all B cell subpopulations. This may reflect the delay in selection and differentiation of potentially autoreactive (ADAMTS13-specific) B cells, resulting in relatively long periods of low disease activity after therapy.

Background Lung involvement is common in patients with Rheumatoid Arthritis (RA), including interstitial lung disease (ILD), pleural disease and small airway disease. There are no full reports in the literature analyzing the influence of Rituximab (RTX) in patients with RA with pre-existing lung disease, although it is a rising question in daily clinical practice. Objectives We aim to evaluate the safety and efficacy of RTX in our cohort of RA patients with pre-existing lung involvement. Methods Retrospective observational study of the RA cohort treated with RTX at University College Hospital, identifying patients treated with RTX with any lung involvement. Data were collected on type of lung disease, mortality, respiratory infections and stabilization/progression of symptoms. Results 264 patients with RA have received RTX in our unit between 1998 and 2012. A total of 38 patients (14%) had lung involvement, 24 of them (63%) were female, mean age was 64 years (range 37-79), mean disease duration was 19 years (range 3-42), mean number of RTX cycles was 4 (range 1-10), total follow up duration was 146.7 patient years (median 2.5 years, range 0.5-13.5). 19 of them (50%) had ILD: 3 usual interstitial pneumonitis (UIP), 5 nonspecific interstitial pneumonitis (NSIP, 2 of those had an overlap antisyntetase syndrome), 4 organizing pneumonia (OP) and 7 undetermined ILD. 15 patients (40%) had bronchiectasis. The remaining 4 patients had diagnosis of chronic obstructive pulmonary disease (COPD), small airway disease, pleural effusion requiring decortication and pleural plaques. 6 of the above patients had concomitant COPD. Lung disease has remained clinically and radiologically stable in most patients. One patient with severe UIP before RTX showed slow lung progression over 4 years of follow up, and Mycophenolate mofetil is being considered. The 2 patients with antisynthetase syndrome have stable NSIP but on combination therapy (1 azathioprine, 1 mycophenolate mofetil). 25 patients (66%) reported respiratory infections but in only 6 of these patients was an increased frequency of infections after starting rituximab treatment noted. 2 of these 6 patients had low serum immunoglobulins (1 IgG only, 1 IgG and IgM). 2 patients had serious infections requiring hospitalization. There were 2 deaths, both in patients with bronchiectasis and multiple comorbidities, none directly related to rituximab treatment. Conclusions RTX seems to be a relatively safe therapy in the cohort of RA patients with lung involvement. There is no definite evidence for improvement in lung involvement in RA patients treated with rituximab, but nor there is data suggesting that RTX can lead to a progression of lung symptoms. Only one patient with severe UIP before RTX showed lung progression after 4 years of follow up. Disclosure of Interest: E. Becerra: None Declared, G. Cambridge: None Declared, M. Leandro Grant/research support from: GSK, Abbott., Consultant for: Roche, Chugai