Attenuation of Follicular Helper T Cell–Dependent B Cell Hyperactivity by Abatacept Treatment in Primary Sjögren's Syndrome
Objective: To assess the effect of abatacept (CTLA-4Ig), which limits T cell activation, on homeostasis of CD4+ T cell subsets and T cell–dependent B cell hyperactivity in patients with primary Sjögren's syndrome (SS). Methods: Fifteen patients with primary SS treated with abatacept were included. Circulating CD4+ T cell and B cell subsets were analyzed by flow cytometry at baseline, during the treatment course, and after treatment was completed. CD4+ effector T cell subsets and Treg cells were identified based on expression of CD45RA, CXCR3, CCR6, CCR4, CXCR5, programmed death 1, inducible costimulator (ICOS), and FoxP3. Serum levels of anti-SSA/anti-SSB and several T cell–related cytokines were measured. Expression of ICOS and interleukin-21 (IL-21) protein was examined in parotid gland tissue at baseline and after treatment. Changes in laboratory parameters and associations with systemic disease activity (EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI]) over time were analyzed using generalized estimating equations. Results: Abatacept selectively reduced percentages and numbers of circulating follicular helper T (Tfh) cells and Treg cells. Other CD4+ effector T cell subsets were unaffected. Furthermore, expression of the activation marker ICOS by circulating CD4+ T cells and expression of ICOS protein in parotid gland tissue declined. Reduced ICOS expression on circulating Tfh cells correlated significantly with lower ESSDAI scores during treatment. Serum levels of IL-21, CXCL13, anti-SSA, and anti-SSB decreased. Among circulating B cells, plasmablasts were decreased by treatment. After cessation of treatment, all parameters gradually returned to baseline. Conclusion: Abatacept treatment in patients with primary SS reduces circulating Tfh cell numbers and expression of the activation marker ICOS on T cells. Lower numbers of activated circulating Tfh cells contribute to attenuated Tfh cell–dependent B cell hyperactivity and may underlie the efficacy of abatacept.
|Persistent URL||dx.doi.org/10.1002/art.40165, hdl.handle.net/1765/101621|
|Journal||Arthritis and Rheumatology|
Verstappen, G.M. (Gwenny), Meiners, P.M, Corneth, O.B.J, Visser, A. (Annie), Arends, S, Abdulahad, W.H. (Wayel H.), … Bootsma, H. (2017). Attenuation of Follicular Helper T Cell–Dependent B Cell Hyperactivity by Abatacept Treatment in Primary Sjögren's Syndrome. Arthritis and Rheumatology, 69(9), 1850–1861. doi:10.1002/art.40165