Patients with T(+/low) NK(+) IL-2 receptor Î³ chain deficiency have differentially-impaired cytokine signaling resulting in severe combined immunodeficiency.

[severe combined immunodeficiency]

X-linked severe combined immunodeficiency (X-SCID ) leads to a T (-) NK (-) B (+) immunophenotype and is caused by mutations in the gene encoding the IL -2 receptor Î³-chain (IL 2 RG ). IL 2 RG (R 222 C ) leads to atypical SCID with a severe early onset phenotype despite largely normal NK- and T -cell numbers . To address this discrepancy , we performed a detailed analysis of T , B , and NK cells , including quantitative STAT phosphorylation and functional responses to the cytokines IL -2 , IL -4 , IL -15 , and IL -21 in a patient with the IL 2 RG (R 222 C ) mutation . Moreover , we identified nine additional unpublished patients with the same mutations , all with a full SCID phenotype , and confirmed selected immunological observations . T -cell development was variably affected , but led to borderline T -cell receptor excision circle (TREC ) levels and a normal repertoire . T cells showed moderately reduced proliferation , failing enhancement by IL -2 . While NK-cell development was normal , IL -2 enhancement of NK-cell degranulation and IL -15 -induced cytokine production were absent . IL -2 or IL -21 failed to enhance B-cell proliferation and plasmablast differentiation . These functional alterations were reflected by a differential impact of IL 2 RG (R 222 C ) on cytokine signal transduction , with a gradient IL -4 <IL -2 /IL -15 <IL -21 . Thus , IL 2 RG (R 222 C ) causes a consistently severe clinical phenotype that is not predicted by the variable and moderate impairment of T -cell immunity or TREC analysis .

Diseases
Validation

Diseases presenting "b" symptom

22q11.2 deletion syndrome

cystinuria

legionellosis

severe combined immunodeficiency

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