Polymorphisms of the gene P2X7 and the role of CD5+ B-lymphocytes in MS

Summary

Multiple sclerosis (MS) is an autoimmune disease which has a strong genetic component. This is evident in the greatly increased incidence of MS and other autoimmune diseases in close relatives of affected patients. Much of this genetic susceptibility is due to the inheritance of certain HLA-genes which switch on a number of biochemical steps to produce a specific protein fragment called a peptide. This specific peptide activates T-cells to attack the nervous system. However, like many autoimmune diseases, the initial immune response expands (spreads) to include many other related peptides which in turn activate B-cells so that additional auto-antibodies appear in the patient’s blood.  This recruitment of B-cells increases inflammation, and may explain progression of disability seen in MS.

Our studies have focused on a different autoimmune disease, Sjogren’s syndrome, as a model for this inflammatory reaction which causes progression in the course of MS, as well as other autoimmune diseases. Sjogren’s patients develop higher amounts and several different autoantibodies in their blood, due to the inflammatory reaction in their salivary glands which causes failure of salivary secretions. We have studied 120 Sjogren's patients and found that one  specific variation (polymorphism) of a gene (the P2X7 gene) is far  more frequent than in normal subjects and is highly associated with the level and range of autoantibodies in the patients blood.  This specific gene polymorphism may predict the degree of salivary gland inflammation in Sjogren’s and we will extend these studies to other autoimmune diseases, in particular MS.