IL2RA – Immunodeficiency due to CD25 deficiency

IL2RA (CD25) deficiency is a rare autosomal recessive disorder caused by biallelic loss‐of‐function mutations in the IL2RA gene, leading to absent cell‐surface CD25 expression and a combined B‐ and T‐cell immunodeficiency phenotype. To date, three unrelated probands have been reported with early‐onset severe infections and autoimmunity who harbor homozygous or compound heterozygous IL2RA variants (PMID:30742970, PMID:29252577, PMID:23416241). Segregation data are limited, consistent with an autosomal recessive inheritance pattern.

Functional studies demonstrate a mechanism of pathogenicity via receptor nullification: flow cytometry and biochemical assays reveal complete absence of CD25 on T cells, impaired IL‐2 signaling, and dysregulated T‐cell activation (PMID:30742970, PMID:23416241). Hematopoietic stem cell transplantation (HSCT) in affected patients results in durable immune reconstitution and resolution of clinical manifestations, supporting clinical utility of early genetic diagnosis and targeted intervention.

Key Take-home: IL2RA genetic testing should be considered in infants with early‐onset combined immunodeficiency and absent CD25 expression, as HSCT offers definitive cure.

References

• Clinical immunology (Orlando, Fla.) • 2019 • CD25 deficiency: A new conformational mutation prevents the receptor expression on cell surface. PMID:30742970
• Eye & contact lens • 2018 • Severe Dry Eye in CD25 Deficiency Syndrome. PMID:29252577
• Clinical immunology (Orlando, Fla.) • 2013 • Human IL2RA null mutation mediates immunodeficiency with lymphoproliferation and autoimmunity. PMID:23416241

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