DIAGNOSIS AND MANAGEMENT OF INHERITABLE DISORDERS OF INTERFERON-γ-MEDIATED IMMUNITY

Two patients with T”B+NK+SCID were shown to have mutations in their IL7Rgenes. This discovery indicates that the defect in IL-7 signaling in XSCID and Jak3-deficient patients is probably responsible for their T-cell defect. Both patients had normal or increased numbers of functional NK cells, confirming that IL-7 is not essential for NK-cell development or function. Both patients had normal numbers of B cells, demonstrating that in humans, IL-7 signaling is not essential for B-cell development; instead other cytokines either are essential or serve a redundant function. The normal B-cell development in JL7R-deficient humans is in contrast to the defective B-cell development in Il7-/-and Il7r-/-mice, and suggests a major difference between humans and mice in B-cell development. As discussed previously, it is speculated that mutations in the IL7gene also may cause T-B+NK+SCID. This article has discussed the range of forms of SCID and has summarized that most patients with SCID have defects related to cytokine signaling (γcdeficiency, Jak3 deficiency, and TL-ZRα deficiency). In the future, it will be interesting to clarify the genetic basis for the remaining undiagnosed forms of SCID and to see how many of these further increase the understanding of cytokine signaling pathways in humans.