Mechanism of Disease in CSU
This animation depicts antibody-mediated mast cell and basophil activation in the pathogenesis of chronic spontaneous urticaria (CSU), and the resultant release of inflammatory cytokines that lead to the symptoms of CSU.
Chronic spontaneous urticaria (CSU) is a debilitating skin condition that affects between 0.5 to 1% of the global population, with women twice as likely to be affected than men.
It is marked by the presence of red, swollen, itchy patches on the skin known as hives or wheals, which typically last less than 24 hours, and recur frequently, for a period exceeding 6 weeks.
Another symptom of CSU is angioedema, which presents as swelling of the deep layers of the skin and occurs in approximately 40% of patients.
CSU occurs due to excessive mast cell and basophil degranulation, with the FcεRI pathway and IgE and IgG antibodies playing a central role in the autoimmune response,
one mechanism which appears to contribute to the pathogenesis of CSU is type I autoimmunity, or autoallergy, which involves autoantigen crosslinking of FcεRI-bound IgE,
while Type 2b autoimmunity is mediated primarily by IgG autoantibodies either crosslinking FcεRI-bound IgE, or free FcεRI receptors.
A key mediator of the FcεRI signaling cascade is Burton’s Tyrosine Kinase, or BTK.
BTK is expressed in cells which play a role in the pathogenesis of CSU, such as mast cells, basophils and B cells.
The role of BTK in CSU is being evaluated due to its role in mediating degranulation and subsequent histamine release from mast cells.
In addition, BTK positively regulates almost any aspect of FcεRI‐mediated MC function including both early‐phase responses such as release of leukotrienes and prostaglandins,
as well as late‐phase MC effector functions, such as release of various cytokines and chemokines and has been associated with their survival, mediating their ability to migrate during IgE‐mediated immune responses.