Abstract
Over the last 4 years, three genetic etiologies of hyper IgE syndromes have been identified: STAT3, DOCK8, and Tyk2. All of these hyper IgE syndromes are characterized by eczema, sinopulmonary infections, and greatly elevated serum IgE. However, each has distinct clinical manifestations. Mutations in STAT3 cause autosomal dominant HIES (Job’s syndrome), which is unique in its diversity of connective tissue, skeletal, and vascular abnormalities. DOCK8 deficiency is characterized by severe cutaneous viral infections such as warts, and a predisposition to malignancies at a young age. Only one individual has been identified with a hyper IgE phenotype associated with Tyk2 deficiency, which is characterized by nontuberculous mycobacterial infection. The identification of these genetic etiologies is leading to advances in understanding the pathogenesis of these syndromes with the goal of improving treatment.
Highlights
Until 2006, the Hyper IgE syndromes remained the last of the major primary immunodeficiencies for which no genetic etiologies were known
In 2009, homozygous and compound heterozygous mutations in DOCK8 were identified in a subset of individuals diagnosed with autosomal recessive Hyper IgE syndrome [4,5]
Autosomal dominant (AD)-HIES can be differentiated from other etiologies of Hyper IgE by its distinctive connective tissue, skeletal, and dental abnormalities (Table 1)
Summary
Until 2006, the Hyper IgE syndromes remained the last of the major primary immunodeficiencies for which no genetic etiologies were known. In 2009, homozygous and compound heterozygous mutations in DOCK8 were identified in a subset of individuals diagnosed with autosomal recessive Hyper IgE syndrome [4,5] Each of these genetic etiologies leads to distinct clinical features, and greater familiarity with these clinical presentations can direct immunologic and genetic studies, and assist with treatment and family counseling. Purulence is found in the airways, but similar to the boils, systemic signs of infection may be minimal, which may lead to late diagnosis of significant infections These infections can usually be treated adequately with antimicrobials directed against the infection organism, the healing of the lung is abnormal, and resultant pneumatocoeles and bronchiectasis may occur (Fig. 1). Some patients do have obstructive lung disease that responds to beta agonist therapy; this is much less common than in other diseases with high IgE such as atopy and DOCK8 deficiency
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