Therapeutic antibody technology targeting membrane IgD as a novel treatment for autoimmune diseases: the underlying mechanisms and corroborating evidence. — The Association Specialists
  1. Schedule
  2. Posters - Tuesday
  3. Therapeutic antibody technology targeting membrane IgD as a novel treatment for autoimmune diseases: the underlying mechanisms and corroborating evidence.

Therapeutic antibody technology targeting membrane IgD as a novel treatment for autoimmune diseases: the underlying mechanisms and corroborating evidence. (326)

Tommie Nguyen 1 2 , Chris Jackson 3 , Jonathan Morris 2 4
  1. Autoimmunity and Immunotherapy Research, Kolling Institute of Medical Research, Sydney, NSW, Australia
  2. Division of Perinatal Research, Kolling Institute of Medical Research, Sydney, NSW, Australia
  3. Sutton Arthritis Laboratory, Kolling Institute of Medical Research, Sydney, NSW, Australia
  4. Northern Clinical School, University of Sydney, Sydney, NSW, Australia

Background: Membrane IgD forms a major part of B-cell receptor complexes. Its wider role in the immune system has been enigmatic. Stimulation of B cells with an anti-IgD antibody can activate B-cells and strong immune responses in vivo. Given the role of B-cells in autoimmune diseases and the profound impact of anti-IgD on B-cells, the potential effects of anti-IgD on autoimmune conditions are intriguing and yet to be explored.
Aim: Our study investigated the potential effects of anti-IgD on autoimmune diseases in vivo.
Methods: Collagen-induced arthritis (CIA) mouse model was used to investigate the effect of anti-IgD in vivo. Evidence of the involvement of IgD+ B-cells in human autoimmune conditions was also reviewed to validate IgD as a potential therapeutic target.
Results: Administration of anti-IgD at the onset of early clinical symptoms as a therapeutic intervention, but not as a prophylactic treatment, significantly ameliorated disease severity and joint pathology. Anti-IgD treatment selectively depleted mature B cells while it augments regulatory B-cell and T-cells subsets in vivo. Treatment significantly reduced of autoantibody productions but did not affect antibody vaccine responses. The presence of B-cell growth factor BAFF/BLyS did not rescue TACI+ B-cells from depletion by anti-IgD. Transgenic anti-IgD mouse model from an independent study confirmed the in vivo mechanism of actions of anti-IgD. Systematic review of recent studies highlighted the evidence of IgD+ B-cells as a major source of autoantibodies that are expanded and activated by elevated BAFF/TACI signals and genetic risk alleles of c-Src tyrosine kinase under autoimmune conditions, supporting their pathological roles in human diseases.
Conclusion: Collectively, anti-IgD monoclonal antibody technology may offer a more specific method of B-cell depletion that also promotes immune tolerance and anti-inflammatory tendencies without compromising general adaptive immune responses.
Disclosure: TN and JM are named as inventors on granted and pending patents regarding anti-IgD.