Finally, inhibitors of T cell activation are strongly associated with RA: polymorphisms in CTLA4, the ligand for CD28 and a negative regulator of T cell activation, lead to altered T cell responses and increased disease susceptibility [10], and a single nucleotide polymorphism in PTPN22, a tyrosine phosphatase expressed by haematopoietic cells that inhibits T cell signalling, is one of the most important non-HLA genetic risk factors for RA [11]. Here, CTLA4 is linked to rheumatoid arthritis.