B cell reconstitution and T helper cell balance after rituximab treatment of active primary Sjögren's syndrome: A double‐blind, placebo‐controlled study

• Published in: Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2011-04, Vol.63 (4), p.1116-1123
• Main Authors: Abdulahad, W. H., Meijer, J. M., Kroese, F. G. M., Meiners, P. M., Vissink, A., Spijkervet, F. K. L., Kallenberg, C. G. M., Bootsma, H.
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Monoclonal, Murine-Derived - pharmacology; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Antirheumatic Agents - pharmacology; Antirheumatic Agents - therapeutic use; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Biological and medical sciences; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; Cell Count; Diseases of the osteoarticular system; Double-Blind Method; Female; Humans; Immunoglobulin D - metabolism; Immunoglobulin M - metabolism; Immunomodulators; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Rituximab; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sjogren's Syndrome - drug therapy; Sjogren's Syndrome - metabolism; Sjogren's Syndrome - pathology; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - metabolism; T-Lymphocytes, Helper-Inducer - pathology; Time Factors; Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism
• ISSN: 0004-3591; 2326-5191; 1529-0131; 2326-5205
• DOI: 10.1002/art.30236

Objective To assess the phenotype of reconstituting B cells after B cell depletion, and to assess the effect of reconstitution on the balance of Treg cells and effector T cells in patients with active primary Sjögren's syndrome (SS). Methods Twenty‐eight patients with primary SS were treated on days 1 and 15 with either rituximab (n = 19) or placebo (n = 9). The frequencies and absolute numbers of circulating B cell subsets, Treg cells, and effector T cells were examined in fresh blood samples by 4‐color flow cytometry at baseline and 5, 12, 24, 36, and 48 weeks after the first infusion. The results in rituximab‐treated patients were compared with those in patients receiving placebo and with those in age‐ and sex‐matched healthy controls (n = 10). Results At baseline, patients with primary SS displayed several abnormalities in B cell homeostasis, including a significant reduction of CD27+ B cells and expansion of CD27– B cells, compared with healthy controls. At week 48 after rituximab treatment, the majority of emerging B cells exhibited a phenotype of transitional B cells. Although recovery of CD27+ memory B cells was delayed after rituximab treatment, a significant increase in Ig class–switched memory B cells within the memory pool was observed. In addition, percentages and absolute numbers of Treg cells and effector T cells, as well as ratios of effector T cells to Treg cells, did not change significantly after rituximab treatment. Conclusion The characteristics of reconstituted B cells in patients with primary SS following depletion by rituximab treatment showed dominance of transitional B cells during the early recovery phase, which corresponds to bone marrow–derived repopulation. The depletion of B cells did not influence the balance of peripheral Treg cells and effector T cells.