DEFECTIVE CAMP DEPENDENT PHOSPHORYLATION IN SYSTEMIC LUPUS ERYTHEMAMOSUS

系统性红斑狼疮（SLE）是一种病因不明的自身免疫性疾病。这种疾病主要影响育龄妇女，最常见的特征是关节炎和皮疹。然而，这是一种可能涉及许多器官系统的疾病，包括免疫系统。患有这种疾病的个体表现出异常的免疫力，并产生针对自身组织成分的异常抗体，称为自身抗体。免疫系统的一个重要组成部分是T淋巴细胞。这种白细胞负责调节抗体和自身抗体的产生，在SLE中功能异常。本实验室发现T淋巴细胞内一种酶缺乏，称为I型蛋白激酶a （PKA-I）。到目前为止，大约80%的SLE患者存在这种酶的T细胞缺乏。我们的研究揭示了构成这种酶的蛋白质成分的异常产生，特别是调节亚基的β亚型。由于蛋白激酶A通过磷酸化过程将ATP中的高能量磷酸盐转移到蛋白质中，并且该过程调节T细胞内许多蛋白质的功能，因此PKA-I的缺乏可能会严重损害T细胞作为B淋巴细胞抗体产生调节器的生理功能。此外，这种酶缺乏可能导致SLE中T细胞的整体功能障碍。

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.