BAFF‐modulated repopulation of B lymphocytes in the blood and salivary glands of RITUXIMAB‐TREATED patients with Sjögren's syndrome

Abstract

Objective. Treatment with rituximab depletes B cells from the peripheral blood (PB) and salivary glands (SGs) of patients with primary Sjögren's syndrome (SS). The purpose of this study was to track the repopulation of B cell subsets in PB as well as their subsequent homing into SGs in patients with primary SS treated with rituximab.Methods. A series of 4-color flow cytometry experiments delineated B cell subsets in 15 patients with primary SS. All were tested on days 8 and 15 of treatment. Nine of the patients were followed up monthly for 10 months, and the remaining 6 patients were followed up monthly for 24 months. Enzyme-linked immunosorbent assays were developed to measure serum levels of BAFF and rituximab. SGs were biopsied at the start of the study and 4 months after treatment in 15 patients, 12 months after treatment in 3 patients, and 24 months after treatment in 2 patients.Results. Baseline serum levels of BAFF correlated inversely (r ‫؍‬ ؊0.92, P < 5 ؋ 10 ؊4 ) with the duration of B cell depletion: the higher the BAFF levels, the shorter the duration of B cell depletion. Conclusion. The timing of B cell repopulation is modulated by BAFF and is followed by reconstitution of the preexisting abnormalities.

Identification and Characterization of a Human CD5+ Pre-Naive B Cell Population

“…ϩϩ IgD ϩ CD5 ϩ immature B cells repopulated during the recovery phase of B cell depletion, and this correlated with an increase in serum BAFF level (42,43). Furthermore, an expanded population of CD38 ϩϩ IgD ϩ CD5 ϩ B cells within the naive B cell compartment was found in peripheral blood of active SLE patients (44).…”

Role of Rituximab Therapy in Glomerulonephritis

“…Tissue resident B cells, especially in lymphoid organs and at sites of inflammation, are more resistant to depletion than circulating cells, and elevated B cell stimulating factor (BLyS), found in active lupus and vasculitis, impair rituximab-induced B cell lysis and associate with shorter clinical responses. 30,31 These factors may explain cases of rituximab failure and the observation that repeated rituximab after minor or partial responses leads to a larger treatment effect. Assessing response is complicated by the variable time to response after rituximab, from days to several months, and increases in conventional therapy may be required to control a deteriorating clinical situation before a response is seen.…”

Oral Aspects of Sjögren’s Syndrome

“…The results of one excellent systematic review about the treatment of SS shows that B cell targeted agents seem to be the most promising future therapy, especially rituximab, which has been used in more than 100 reported cases. Agents that block B cell-activating factor of the tumor necrosis factor family may also be a promising therapy (41,42). Advances in knowledge of the molecular mechanisms involved in the etiopathogenesis of Sjögren's syndrome may allow the development of more effective, highly selective therapies without the adverse effects often associated with standard, less-selective drugs (41).…”