B-Cell Depletion in Wegener’s Granulomatosis

Abstract

Wegener's granulomatosis (WG) is a chronic, relapsing, systemic necrotizing vasculitis with typical pathologic findings of granulomatous inflammation and pauci-immune vasculitis. Untreated, the condition has a very high mortality, and contemporary treatment strategies carry a high risk of treatment-related morbidity. Antineutrophil cytoplasmic antibodies (ANCA) play a central role in the pathogenesis of the disease. It is unclear how ANCA develop, but B cells are of major importance in the disease pathogenesis as precursors of ANCA-producing plasma cells and, possibly, also as antigen-presenting and cytokine-producing cells. Therefore, the use of B-cell depletion therapy, e.g., with rituximab appears to be an attractive treatment option in WG. Several small clinical trials and case reports show promising results with a high rate of clinical remissions achieved in patients that were refractory to or intolerant of conventional treatment regimens. However, granulomatous manifestations seemed to be less responsive to B-cell depletion therapy. B-cell depletion therapy was generally well tolerated. A large prospective, randomized, double-blind clinical trial evaluating the efficacy of B-cell depletion therapy in WG is pending.

Off‐Trial Evaluation of the B cell–Targeting Treatment in the Refractory Cases of Antineutrophil Cytoplasmic Antibodies (ANCA)‐Associated Vasculitis: Long‐Term Follow‐Up from a Single Centre

“…We observed significant decrease in PR3 and ANCA titres following RTX treatment in line with several other studies [11,27]. Depletion of B lymphocytes most probably decreases the ANCA production by eliminating the precursors of potential 418 Rituximab in ANCA-Associated Vasculitis ANCA-producing plasma cells.…”

“…Depletion of B lymphocytes most probably decreases the ANCA production by eliminating the precursors of potential 418 Rituximab in ANCA-Associated Vasculitis ANCA-producing plasma cells. Moreover, the role of B lymphocytes in other aspects of immune regulation such as antigen presentation, cytokine production and co-stimulatory signalling of T cells possibly contributes to the pathogenesis of the disease [27].…”

New laboratory criterion for the differential diagnosis of sarcoidosis and pulmonary tuberculosis

“…According to O'Shea et al, during active tuberculosis, a decrease in memory B cells was detected, while the frequency of "naive" B cells was unaltered (52). Impaired memory and "naïve" B cells distribution have been described in some autoimmune diseases (38,39).…”

Wegener’s Granulomatosis Mimicking Pulmonary

“…It appears to be more effective in the vasculitic rather than the granulomatous phase [33][34][35][36] . 15-desoxyspergualin is a synthetic derivative of spergualin, a protein from Bacillus laterosporus that is capable of preventing T-and B-cell maturation and has been used with some success in refractory cases 37,38 . Data about stem cell transplant is very limited 31 .…”