Abnormal lnterferon-𝛽 Function in Multiple Sclerosis: Evaluation of Four Signaling Proteins of the JAK-STAT Pathway in Mononuclear Celis
The diverse class of autoimmune diseases result from improper functioning of the T cells of the immune system, whereby they aberrantly recognize specific cells of one's body as foreign, and destroy them. Multiple sclerosis (MS), one such autoimmune disease, is characterized by T cell mediated destruction of the myelin sheaths surrounding neurons of the brain and spinal cord. There is some evidence that mononuclear cells of MS victims exhibit compromised interferon signaling, which is a pathway that normally helps these cells to regulate antiviral immune responses. Presently, an effective treatment in MS is Interferon-𝛽 induction therapy. Although the exact mechanism by which Interferon-𝛽 alleviates symptoms is unknown, we tested the hypothesis that altered levels of certain critical proteins involved in the interferon signaling cascade may exist between MS patients and healthy individuals. Extracted proteins from white blood cells of both MS and normal patients were stained with fluorescent antibodies specific for four well known JAK/STAT signaling proteins: pSTAT 1, p48, ICSBP and SHP 1. Results showed that MS patients expressed similar levels of p48 and ICSBP, both transcription factors in the JAK/ISTAT pathway. In contrast, in MS patients, pSTAT 1 was profoundly overexpressed, while SHP 1 was underexpressed, when compared to healthy patients. These findings are significant, since abnormalities of these activating and deactivating proteins of the Interferon-𝛽 mediated signaling cascade could cause severe immune disregulation. Further molecular insight into this pathway and the roles of these proteins in relation to MS may advance understanding of the disease.