Early BAFF receptor blockade mitigates murine Sjögren's syndrome: Concomitant targeting of CXCL13 and the BAFF receptor prevents salivary hypofunction

Clinical Immunology : the Official Journal of the Clinical Immunology Society
Arjun SharmaJill M Kramer

Abstract

Sjögren's syndrome (SS) is a debilitating autoimmune disease. Patients with SS may develop xerostomia. This process is progressive, and there are no therapeutics that target disease etiology. We hypothesized BAFF receptor (BAFFR) blockade would mitigate SS disease development, and neutralization of CXCL13 and BAFF signaling would be more efficacious than BAFFR blockade alone. We treated NOD/ShiLtJ SS mice with soluble BAFF receptor (BAFFR-Fc) or anti-CXCL13/BAFFR-Fc in combination, prior to the development of clinical disease. Our results show treatment with BAFFR-Fc reduced peripheral B cell numbers and decreased sialadenitis. In addition, this treatment reduced total serum immunoglobulin as well as IgG and IgM specific anti-nuclear autoantibodies. NOD/ShiLtJ mice treated with BAFFR-Fc and anti-CXCL13 antibody were protected from salivary deficits. Results from this study suggest blockade of CXCL13 and BAFFR together may be an effective therapeutic strategy in preventing salivary hypofunction and reducing autoantibody titers and sialadenitis in patients with SS.

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Citations

Oct 16, 2016·Journal of Clinical Medicine·Julian Lawrence AmbrusAmmon Peck
Nov 28, 2016·Biochemical and Biophysical Research Communications·Ting XuMin Wu
Sep 13, 2019·The Journal of Clinical Endocrinology and Metabolism·George J KahalyYanling He
Sep 17, 2017·Annals of the Rheumatic Diseases·Shu-Fang Wang-RenaultJörg Tost
Nov 29, 2016·Current Oral Health Reports·Anne Isine Bolstad, Kathrine Skarstein
Jun 9, 2020·Clinical and Experimental Medicine·F J Carrillo-BallesterosEdith Oregon-Romero
Jan 24, 2019·Journal of Immunology Research·Jeremy Kiripolsky, Jill M Kramer
Mar 27, 2020·ImmunoTargets and Therapy·Noha Mousaad ElemamAzzam A Maghazachi
Sep 8, 2018·Frontiers in Immunology·Deepak A Rao
Feb 21, 2019·Experimental and Therapeutic Medicine·Francisco Josué Carrillo-BallesterosClaudia Azucena Palafox-Sánchez
Apr 4, 2021·International Journal of Molecular Sciences·Toshimasa ShimizuAtsushi Kawakami
Sep 11, 2021·Alimentary Pharmacology & Therapeutics·Albert J Czaja

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