CD40 drives early-life immune dysregulation--new insights into autoimmune pathogenesis

WRITTEN BY

Rachel Ettinger, Senior Scientist, RIA

Autoimmunity may be happening much earlier than we previously thought. This was our hypothesis that we took into the lab in collaboration with leading experts.  This week, the findings from our pre-clinical work were published in Science Translational Medicine.

The results suggest that in diseases such as Sjögren’s syndrome, thyroiditis, and type 1 diabetes, lymphocytes that prompt autoimmunity may be lurking in immune compartments such as the spleen early in life, ultimately trafficking to target tissues resulting in disease pathology.

These data illuminate the role of CD40 and how it contributes to early-life immune dysregulation and organ-specific autoimmunity.  Early blockade of CD40L potently inhibited autoimmune manifestations in three different animal models.  A single early treatment with anti-CD40L mAb prevented the spontaneous development of splenic germinal centers, and contributed to the inhibition of autoantibody production and inflammation of target tissues.

These data were further corroborated by early life splenectomy, which similar to CD40L blockade, resulted in inhibition of autoimmune manifestations.  These findings suggest that blockade of CD40/CD40L could have a positive impact on the treatment of autoimmune diseases that are predated by the appearance of autoantibodies.

Our studies exemplify the importance of following the science from sound hypotheses to new discoveries.  We are now looking ahead to other basic research questions related to different drivers of disease pathogenesis and the potential interplay of CD40 with other immunologic molecules with the hope to discover new treatments for the clinical need of patients with autoimmune diseases.

You can read the full study here.

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