Hyper-IgE (Job) syndrome, chronic mucocutaneous candidiasis and the IL-12/IFN-γ axis !

Topic

Some inborn defects knock out a single branch of T-cell help, giving a very specific infection pattern: Staphylococcus, Candida or mycobacteria.

Updated 2026-11-01

What it is

These inborn errors of immunity break narrow pathways rather than the whole immune system. Loss of the IL-17 (Th17) pathway leaves the skin and mucosa open to Staphylococcus aureus and Candida, as in autosomal dominant hyper-IgE syndrome (STAT3) and chronic mucocutaneous candidiasis. Loss of the IL-12/IFN-γ loop leaves macrophages unable to kill mycobacteria and Salmonella. Recognising the pattern points to the right genetic test.

Key facts

Th17 cells (IL-17, IL-22) recruit neutrophils and make epithelial antimicrobial peptides: they guard skin and mucosa against S. aureus and Candida.
In STAT3 hyper-IgE, abscesses are «cold» because the local inflammatory signals are weak.
IL-12 from macrophages drives IFN-γ from T and NK cells, and IFN-γ activates macrophages to kill intracellular bacteria: a loop that mycobacteria require to be controlled.
Anti-TNF and anti-IL-17 biologics reproduce part of these patterns (tuberculosis reactivation; mucocutaneous candidiasis).

Narrow T-cell pathway defects and their infections

Disorder	Gene or pathway	Typical infections	Clues
Autosomal dominant hyper-IgE syndrome (Job syndrome)	STAT3 loss of function: Th17 cells fail to develop	Skin abscesses with little inflammation (cold abscesses) and pneumonia by S. aureus; mucocutaneous Candida	Eczema from infancy, very high IgE, eosinophilia, pneumatoceles, retained primary teeth, coarse face, fractures and scoliosis
DOCK8 deficiency (autosomal recessive hyper-IgE)	DOCK8: combined T- and B-cell defect	Severe viral skin infections (herpes simplex, papillomavirus, molluscum), sinopulmonary infections	Eczema, high IgE, food allergies, early cancers; no skeletal or dental signs
Chronic mucocutaneous candidiasis	IL-17 pathway: IL17RA, IL17F, STAT1 gain of function; AIRE in APS-1	Persistent Candida of the mouth, nails, skin and genitals; rarely invasive	In APS-1: candidiasis + hypoparathyroidism + adrenal insufficiency, with autoantibodies against IL-17 and IL-22
CARD9 deficiency	CARD9: signalling of fungal lectin receptors (Dectin-1)	Invasive Candida (including the central nervous system) and deep dermatophyte infection	Severe fungal disease in a person with otherwise normal immunity
Mendelian susceptibility to mycobacterial disease	IL-12/IFN-γ axis: IL12RB1, IL12B, IFNGR1, IFNGR2, STAT1 loss of function	Disseminated BCG after vaccination, non-tuberculous mycobacteria, Salmonella; severe tuberculosis	BCG adenitis or disseminated BCG in an infant; recurrent non-typhoid Salmonella

Clinical notes

Colombia vaccinates newborns with BCG, so disseminated BCG or BCG adenitis in an infant should raise suspicion of an IL-12/IFN-γ defect or SCID.
STAT3 hyper-IgE: pneumonias heal with pneumatoceles that may later become infected by Aspergillus or Pseudomonas.
Very high IgE alone is not diagnostic: it is also seen in atopic dermatitis and helminth infection.
APS-1 (AIRE) links immunodeficiency and autoimmunity: autoantibodies against cytokines cause the candidiasis.

Test yourself

Think of the answer, then tap the question to see it.

Which gene is mutated in autosomal dominant hyper-IgE (Job) syndrome and which T-cell subset fails?

STAT3; Th17 cells do not develop.

Why are abscesses in Job syndrome described as cold?

Weak local inflammatory signalling means little redness, heat and pain despite pus.

An infant develops disseminated infection after BCG vaccination. Which pathway should be tested?

The IL-12/IFN-γ axis (IL12RB1, IFNGR1/2, STAT1), and SCID must also be excluded.

Which defect gives chronic mucocutaneous candidiasis with hypoparathyroidism and adrenal insufficiency?

AIRE mutation (APS-1), with autoantibodies against IL-17 and IL-22.

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Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.

Sources: Autosomal dominant hyper-IgE syndrome: MedlinePlus Genetics (U.S. National Library of Medicine (MedlinePlus), 2026); 19.4 Immunodeficiency (OpenStax (Microbiology), 2016); 21.5 The Immune Response against Pathogens (OpenStax (Anatomy and Physiology 2e), 2022).

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