Table 1.

Key features of genetic immune dysregulation syndromes

Disorder	APECED	IPEX	CD25 deficiency	STAT5b deficiency	Itch deficiency	IL-10R or IL-10 deficiency
Gene product	AIRE-1	FOXP3	CD25	STAT5b	ITCH/AIP4	IL10R1, IL10R2, IL-10
Number of patients reported	>150	>70	3 patients (2 families)	10 patients (8 families)	10 patients (1 family)	IL10R: 4 patients (3 families)
						IL-10: 2 patients (2 families)
Common clinical features (present in >50% of patients)	Hypoparathyroidism	Enteropathy	Enteropathy	Marked growth failure	Chronic lung disease/interstitial pneumonitis	Severe, early-onset, fistulating colitis
	Adrenal insufficiency	Dermatitis (eczema)	Recurrent/persistent viral infections (CMV, EBV, etc.)	Chronic lung disease/interstitial pneumonitis	Hepatosplenomegaly	Follicular dermatitis
	Mucocutaneous candidiasis	Endocrinopathy	Hepatomegaly	Eczematous rash	Macrocephaly
			Lymphadenopathy		Dysmorphic facies
Additional clinical features	Gonadal insufficiency	Autoimmune hemolytic anemia, thrombocytopenia, or neutropenia	Eczema	Diarrhea/enteropathy	Hypothyroidism	Infections (pneumonia, otitis media, bronchitis, renal abscess, etc.), may be related to immune suppression
	Diabetes mellitus	Autoimmune hepatitis	Persistent thrush, Candida esophagitis	Autoimmune thyroid disease	Hepatitis
	Pernicious anemia	Renal insufficiency		Recurrent or severe viral infections	Enteropathy
	Alopecia areata			Facies: prominent forehead and saddle nose	Insulin-dependent diabetes
	Vitiligo
	Autoimmune hepatitis
	Interstitial lung disease
	Keratitis
Useful laboratory or diagnostic features	Hypocalcemia	Eosinophilia	CD25 expression on T cells absent or low (flow cytometry)	Normal plasma growth hormone	Itch mutation present	Tyrosine phosphorylation of STAT3 absent or decreased in cells stimulated with IL-10 (flow cytometry)
	Hyperphosphatemia	Very elevated IgE	IgE typically normal	Very low plasma IGF-1 and IGFBP-3
	Low plasma cortisol	FOXP3 expression in CD4+ T cells typically low (flow cytometry)	Poor T cell proliferation	Elevated Prolactin		Immune workup typically normal
	High plasma ACTH	FOXP3 mutation present	CD25 mutation present	Mild/moderate T cell lymphopenia		IL10 or IL10R mutation present
	Antibodies to type I interferons (IFN-α or ω) typically present			Decreased NK cells
				STAT5B mutation present
	AIRE-1 mutation present
Treatments	Symptomatic care	Symptomatic care	Symptomatic care	Growth hormone ineffective	Close pulmonary follow-up/PFT’s	Immune suppression largely ineffective
	Antifungal therapy	T cell directed immune suppression (calcineurin inhibitors or rapamycin)	Immune suppression	IGF-1 therapy theoretically effective but untried	Immune suppression	Surgical management of fistulae and abscesses
	Possibly Rituximab for autoantibody mediated disease			IVIG
		Rituximab for autoantibody mediated disorders		Antimicrobials
				Immune suppression
				Close pulmonary follow-up/PFT’s
Bone marrow transplant	Not routinely used	Effective (preferably early)	Effective	Probably effective for immunologic features but untried	Theoretically effective based on murine studies but untried	Effective