DEFECTIVE CAMP DEPENDENT PHOSPHORYLATION IN SYSTEMIC LUPUS ERYTHEMAMOSUS

Wake Forest University, Winston Salem NC

Investigators

Linked publications & trials

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown cause. The disease predominantly affects women in the childbearing age, and is most often characterized by arthritis and skin rashes. However, it is a disease that can potentially involve many organ systems, including the immune system. Individuals with this disorder exhibit abnormal immunity, and produce abnormal antibodies directed against components of their own tissues termed autoantibodies. An important component of the immune system is the T lymphocyte. This white blood cell, which is responsible for regulating the production of antibodies and autoantibodies, functions abnormally in SLE. This laboratory has identified a deficiency of an enzyme within the T lymphocyte, termed type I protein kinase A (PKA-I). About 80% of all subjects tested to date with SLE have a T cell deficiency of this enzyme. Our research reveals that there is abnormal production of the protein components that comprise this enzyme, particularly the beta isoform of the regulatory subunit. Because protein kinase A transfers high energy phosphates from ATP to proteins in a process called phosphorylation and this process regulates the functions of many proteins within the T cell, a deficiency of PKA-I may significantly impair the capacity of the T cell to carry out its physiologic function as a regulator of antibody production by B lymphocytes. Moreover, this enzyme deficiency may contribute to the overall dysfunction of T cells in SLE.