Genomic sequencing had shown that the T cells in these children carry mutations in a gene called IL2RA
. This gene contains instructions for a cell-surface receptor essential for the development of regulatory T cells, or Tregs, which keep other immune cells in check and prevent autoimmunity.
These discoveries are associated with MS 'risk' genes discovered in the latest analysis of experimental autoimmune encephalomyelitis, which show that for 9 different genes associated with MS (MS gene susceptibility), Bach 2, IL2ra
, Irf8, Merkk, Odf3b, Plek, Rgsl, Slc30a7 and Thada confirmation can be made about their differential regulation in pathogenic CD4 T cells.
Several predisposing genetic loci including CTLA4, HLA, and IL2RA
have been identified and certain environmental factors like radioiodine treatment, iodine deficiency, and cigarette smoking have been implicated in pathogenesis of AITDs [2, 3].
Mai et al., "CpG methylation changes within the IL2RA
promoter in type 1 diabetes of childhood onset," PLoS One, vol.
The PPI network consists of 27 upregulated proteins including LCK, CD3G, CD3E, CD3D, IFNG, VAV1, TNF, B2M, CXCR3, CCR5, CCL5, CXCL9, CXCL10, CXCR4, GNG2, IL1B, IL12B, IL2RB, IL2RA
, IL2RG, STAT1, CD8A, CD86, PTPRC, PIK2CG, CD44, and HLADPA1 and 1 downregulated protein EGF.
We analyzed the CaN pathway gene variants previously associated with ex-vivo TAC PD in healthy volunteers (8) (i.e., PPIA rs8177826 and 6850; PPP3CA rs45441997; IL2RA
rs10795791, 11594656, and 35285258), as well as 2 additional key genes of TAC pharmacodynamics (PPP3R1 rs4519508 andFKBP1A rs141252617).
This US FDA approval was based on the company's two randomised multicentre studies comparing Thymoglobulin to interleukin-2 receptor antagonists (IL2RA
: basiliximab or daclizumab) in deceased donor kidney transplant recipients.
Yang et al., "Type 1 diabetes-associated IL2RA
variation lowers IL-2 signaling and contributes to diminished CD4+CD25+ regulatory T cell function," Journal of Immunology, vol.
ATL cell lines produce a soluble factor that stimulates the expression of interleukin-2 receptor alpha chain (IL2RA
) by HTLV1-positive/ATL-negative cells, the ATL-derived factor (ADF) .
In a recent study attempting to determine the roles of rare variants in RA, deep exon sequencing of 25 biological candidate genes from GWAS-identified loci resulted in the identification of an accumulation of missense variants in the IL2RA
and IL2RB genes.
In addition PTPN22 (protein tyrosin phosphatase), CTLA4, and IL2RA
genes have also been shown as candidates for T1DM due to their role in T-cell signaling.
As an example, in the transcript variant X1 (XM_005252446) of the Human IL2RA
the canonical 3'ss TTCCAG immediately upstream of exon 4 is silenced and the fourth exon (216 nt; 72 aa) of the canonical sequence (NM_000417) is lacking in this variant.