Interleukin-2 Receptor Alpha Chain (CD25) Deficiency

CD25 deficiency is an inborn error of immunity presenting with increased susceptibility to infections and chronic diarrhea, lymphadenopathy, and hepatosplenomegaly, due to immunedysregulation. The disease is due to mutations in the CD25 gene and it is an autosomal recessive syndrome. The clinical manifestations are associated with decreased peripheral blood lymphocyte numbers, altered CD4/CD8 ratio, reduced responsiveness to anti-CD3 stimulation, and tissue lymphocytic infiltration. B-cell development are not affected, and no decrease in the serum immunoglobulins was observed. CD25 protein expression was completely removed. The lack of CD25 on regulatory T cells impairs their peripheral survival and on effector T cells impairs their ability to expand following an immune response to pathogens. The disease resembles immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, due to FOXP3 gene mutations. CD25 deficiency is a rare disease, with a prevalence estimated at less than one case per million births ( http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=169100 ). Most patients develop the disease in early infancy. However, we and others are studying a family in which three siblings, carry compound heterozygous CD25 mutations, and only two of them developed autoimmune manifestations without increased propensity to infections. This suggests that the phenotype of the patients may vary depending on their genotype.