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97 Deletion of taci protects against autoimmune disease in lupus-prone mouse models with different disease mechanisms
  1. EX Lim1,
  2. W Figgett1,
  3. F Mackay1 and
  4. M Hibbs2
  1. 1Peter Doherty Institute- The University of Melbourne, Department of Immunology, Melbourne, Australia
  2. 2Monash University, Department of Immunology and Pathology, Melbourne, Australia

Abstract

Background and aims Systemic lupus erythematosus (SLE) is a debilitating autoimmune disease driven by production of autoantibodies which targets various organs including the kidney. SLE is notoriously heterogeneous, arising from numerous possible mechanisms and there is no current efficient treatment. Many of these distinct mechanisms can be reproduced in different mouse models of SLE. Excess production of the B cell activating factor of the TNF family (BAFF) has been previously implicated as a disease-associated factor in a subset of SLE patients, particularly by signalling through transmembrane activator and cyclophilin ligand interactor (TACI) to drive pro-inflammatory autoantibody production. We investigated if deletion of TACI in various mouse models of SLE would be protective.

Methods Flow cytometry was used to characterise B cell and antibody-producing plasma cell subsets in these mouse models. Autoantibody detection and serum cytokine levels were measured using ELISA whilst kidney histopathology was assessed using paraffin-embedded kidney sections.

Results Indeed, the results show that deletion of TACI in BAFF-transgenic mice and other mouse models with separate disease mechanisms, prevented disease by restricting autoantibody production and decreased kidney pathology. Loss of TACI protected these mice from disease whilst maintaining B cell numbers.

Conclusions These data provide increased support for choosing TACI as a key target for therapeutic intervention, which may be applicable in treating multiple subtypes of SLE. This would offer treatment efficacy without the serious adverse events linked with extensive loss of B cells.

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