CD25 deficiency
| CD25 deficiency | |
|---|---|
| Other names | Interleukin-2 receptor alpha chain deficiency |
 | |
| This condition is inherited in an autosomal recessive manner. | |
CD25 deficiency or interleukin 2 receptor alpha deficiency is an immunodeficiency disorder associated with mutations in the interleukin 2 receptor alpha (CD25) (IL2RA) gene. The mutations cause expression of a defective α chain or complete absence thereof, an essential part of high-affinity interleukin-2 (IL-2) receptors. The result is a syndrome described as IPEX-like[1] or a SCID.[2]
In one patient, deficiency of CD25 on CD4+ lymphocytes caused significantly impaired sensitivity to IL-2. This was demonstrated by a lack of measurable response in anti-inflammatory interleukin-10 (IL-10) secretion to low-dose IL-2 incubation. Greatly reduced IL-10 secretion compared to healthy humans results in a syndrome comparable to IPEX syndrome, a type of autoimmunity which is caused by FoxP3 transcription factor dysfunction. In addition to IPEX-like symptoms, CD25 deficiency increases susceptibility to viral infections[1] and possibly fungal and bacterial infections.
As IL-2 is an important inducer of lymphocyte proliferation, the absence of highly sensitive IL-2 receptors may also significantly hinder activation and clonal expansion of CD8+ and CD4+ lymphocytes and NK cells.[2] One case also reported the absence of CD1, a MHC-like glycoprotein involved in the presentation of lipid antigens to T cells, in a CD25 deficient patient. Furthermore, chronic upregulation of anti-apoptotic Bcl-2 in thymocytes was also described possibly allowing autoreactive T cells to escape deletion.[3]
References
- ^ a b Caudy AA, Reddy ST, Chatila T, Atkinson JP, Verbsky JB (2007). "CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked–like syndrome, and defective IL-10 expression from CD4 lymphocytes". J Allergy Clin Immunol. 119 (2): 482–7. doi:10.1016/j.jaci.2006.10.007. PMID 17196245.
- ^ a b Bonilla FA, Geha RS (2003). "12. Primary immunodeficiency diseases". J Allergy Clin Immunol. 111 (2 Suppl): S571-81. doi:10.1067/mai.2003.86. PMID 12592303.
- ^ Sharfe N, Dadi HK, Shahar M, Roifman CM (1997). "Human immune disorder arising from mutation of the alpha chain of the interleukin-2 receptor". Proc Natl Acad Sci U S A. 94 (7): 3168–71. Bibcode:1997PNAS...94.3168S. doi:10.1073/pnas.94.7.3168. PMC 20340. PMID 9096364.