Hyperimmunoglobulinemia E Syndrome

Basics

DESCRIPTION

Hyperimmunoglobulinemia E syndrome (HIES) is a primary immunodeficiency with markedly elevated serum IgE associated with recurrent skin abscesses, pulmonary infections, and eczematoid dermatitis.

EPIDEMIOLOGY

Rare
True incidence and prevalence is unknown; affects equal numbers of males and females

RISK-FACTORS

GENETICS

Autosomal dominant cases (AD-HIES) are caused by mutations in signal transducer and activator of transcription 3 (STAT3).
Autosomal recessive cases (AR-HIES) have mutations in the dedicator of cytokinesis-8 gene (DOCK8).
AR-HIES can also be secondary to tyrosine kinase 2 (TYK2) signaling alterations and phosphoglucomutase 3 (PGM3) mutations.
AR-HIES patients differ in phenotype from AD-HIES patients.
Sporadic cases occur.

PATHOPHYSIOLOGY

STAT3 is integral in secretion and signaling of multiple cytokines involved in proinflammatory and anti-inflammatory responses.
A failure of Th17 cell differentiation and failure of IL-17 secretion makes patients susceptible to Candida infections.
Deficiency in IL-11 signaling results in tooth abnormalities and craniosynostosis.
DOCK8 deficiency results in failure of dendritic cells to migrate to lymph nodes and affects long-term memory B cells and viral-specific CD8+ T cells.

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