Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
APRIL and BAFF Levels After Rituximab Treatment in Patients with Primary Sjgren's Syndrome: A Placebo-Controlled Clinical Trial.
Pollard, Rodney, Abdulahad, Wayel H., Huitema, Minke G., Visser, Annie, Meijer, Jiska, Burgerhof, Hans, Spijkervet, Fred
Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by infiltrates of B- and T-cells in salivary and lacrimal glands, eventually leading to destruction of these glands. B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL), members of the tumor necrosis factor (TNF)-ligand family, are essential for development, maturation and survival of B-cells. To assess the effect of rituximab (anti-CD20) treatment on BAFF and APRIL levels in patients with pSS
In a randomised double-blinded placebo-controlled trial, pSS patients were treated on day 1 and 15 with either rituximab (n= 20) or placebo (n= 10). To minimise side effects (infusion reactions, serum sickness), all patients were pre-medicated with methylprednisolone and oral prednisone. Fresh blood samples were collected at various time points (before, 5, 12, 36 and 48 weeks following treatment). Age- and sex-matched blood samples were collected from healthy controls (n=10). In addition, paired incisional parotid biopsies were taken in 10 patients (5 rituximab, 5 placebo) before and 12 weeks after rituximab/placebo treatment. Percentages and numbers of B cell subsets were examined by four-color cytometry. BAFF and APRIL levels were assessed by enzyme-linked immunosorbent assay. BAFF expression in salivary glands was revealed by immunohistochemistry of parotid gland sections.
Complete depletion of B-cells in serum was observed in the rituximab treated group, while B-cell levels remained unchanged after placebo treatment. B-cells reappeared in the rituximab treated group within 24 to 48 weeks after treatment. At baseline, both BAFF and APRIL serum levels were significantly (p<0.01) increased in pSS-patients in comparison to healthy controls. Strikingly, long-term elevated serum levels of BAFF (3.04.0 fold, p<0.05) were observed up to 36 weeks following rituximab treatment followed by a complete return to baseline levels by week 48. In contrast, BAFF serum levels were almost unchanged in the placebo group, except for a slight (0.5 fold, p<0.05) increase in BAFF levels at week 5 after treatment, likely due to methylprednisolone administration. APRIL levels in serum were hardly affected by the rituximab treatment, although there was a slight increase (0.25 fold, p<0.05) at 12 weeks after treatment, followed by a rapid return to baseline levels. Furthermore, at least 3 out of 5 pSS showed an increase in BAFF expression in parotid glands after rituximab treatment at tissue level.
These data show that both BAFF and APRIL levels are increased in serum of pSS patients, indicating that both cytokines could be involved in the pathogenesis of pSS, possibly by triggering the activation and differentiation of self-antigen-driven autoimmune B-cells. Importantly, we also demonstrate that there is a significant increase of BAFF in blood and salivary glands after rituximab therapy, whereas APRIL levels are almost unaffected by the treatment and remain elevated during the entire study period. This observation might be important for treatment strategies with biologicals affecting BAFF, T-cell co-stimulation and/or B-cell depletion. Extended data are in progress and will be presented at the ACR meeting.
To cite this abstract, please use the following information:
Pollard, Rodney, Abdulahad, Wayel H., Huitema, Minke G., Visser, Annie, Meijer, Jiska, Burgerhof, Hans, et al; APRIL and BAFF Levels After Rituximab Treatment in Patients with Primary Sjgren's Syndrome: A Placebo-Controlled Clinical Trial. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1752