Protein Tyrosine phosphatase receptor type C (CD45) C77G mutation and susceptibility to multiple sclerosis, autoimmune and infectious diseases

The protein tyrosine phosphatase receptor type C (PTPRC), also known as CD45 molecule, is a glycoprotein expressed on the cell surface of all hematopoietic cells except erythrocytes. Functionally, PTPRC is an immunomodulatory gene required for the efficient development of the immune system where it is involved in antigen receptor signal transduction. Several single nucleotide polymorphisms of the PTPRC gene have been described. In humans, the most extensively reported PTPRC polymorphism is the C77G point mutation in exon 4, and this nucleotide transversion causes abnormal PTPRC splicing, thus resulting in an altered expression pattern of isoforms with enhanced expression of high-molecular-weight isoforms (CD45RA, CD45RB, and CD45RC) and decreased low-molecular-weight CD45RO molecules. This altered expression pattern of isoforms can have significant effects on immune function, autoimmunity, and viral infections. Previous epidemiological studies have investigated the relationship between the C77G variant and several diseases. An association between this polymorphism and susceptibility to multiple sclerosis (MS) has been reported in some research papers, thereby suggesting a possible etiologic role of PTPRC in the development of this disease. Subsequent studies performed in other populations, including family-based and case-control studies, could not replicate this relationship between MS and the C77G point mutation, thus suggesting that more statistically powered studies are needed to confirm such an association or not. Furthermore, C77G polymorphism has been suggested to contribute to the development of some infective or autoimmune disorders. As individuals with C77G polymorphism may have increased susceptibility to HIV-1 infection, the frequency of this variant has been investigated in hepatitis C, histiocytosis, and autoimmune diseases, with contrasting results. Although PTPRC represents one of the modifier genes of human autoimmunity, further studies are needed to explain the exact role of PTPRC gene C77G variant in the contribution to the alteration of immune responses in infectious and autoimmune diseases.