[HTML][HTML] Active systemic lupus erythematosus is associated with a reduced cytokine production by B cells in response to TLR9 stimulation
J Sieber, C Daridon, SJ Fleischer, V Fleischer… - Arthritis Research & …, 2014 - Springer
Arthritis Research & Therapy, 2014•Springer
Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease associated with
a break in self-tolerance reflected by a production of antinuclear autoantibodies. Since
autoantibody production can be activated via nucleic acid Toll-like receptor 9 (TLR9), the
respective pathway has been implicated in the development of SLE and pathogenic B cell
responses. However, the response of B cells from SLE patients to TLR9 stimulation remains
incompletely characterized. Methods In the current study, the response of B cells from SLE …
a break in self-tolerance reflected by a production of antinuclear autoantibodies. Since
autoantibody production can be activated via nucleic acid Toll-like receptor 9 (TLR9), the
respective pathway has been implicated in the development of SLE and pathogenic B cell
responses. However, the response of B cells from SLE patients to TLR9 stimulation remains
incompletely characterized. Methods In the current study, the response of B cells from SLE …
Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disease associated with a break in self-tolerance reflected by a production of antinuclear autoantibodies. Since autoantibody production can be activated via nucleic acid Toll-like receptor 9 (TLR9), the respective pathway has been implicated in the development of SLE and pathogenic B cell responses. However, the response of B cells from SLE patients to TLR9 stimulation remains incompletely characterized.
Methods
In the current study, the response of B cells from SLE patients and healthy donors upon TLR9 stimulation was analyzed in terms of proliferation and cytokine production and correlated with the lupus disease activity and anti-dsDNA titers.
Results
B cells from SLE patients showed a reduced response to TLR9 agonist compared to B cells from healthy donors in terms of proliferation and activation. B cells from SLE patients with higher disease activity produced less interleukin (IL)-6, IL-10, vascular endothelial growth factor, and IL-1ra than B cells from healthy donors. Further analyses revealed an inverse correlation of cytokines produced by TLR9-stimulated B cells with lupus disease activity and anti-dsDNA titer, respectively.
Conclusion
The capacity of B cells from lupus patients to produce cytokines upon TLR9 engagement becomes less efficient with increasing disease activity, suggesting that they either enter an exhausted state or become tolerant to TLR stimulation for cytokine production when disease worsens.
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