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[Immunology](https://durgical.com/en/immunology/) · [Immunodeficiencies](https://durgical.com/en/immunology/#a-immunodeficiency)

# 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

## Key points

- Job syndrome = STAT3: no Th17, cold staphylococcal abscesses, eczema, very high IgE, retained primary teeth, pneumatoceles.
- Chronic mucocutaneous candidiasis = defect of the IL-17 pathway (or AIRE autoantibodies to IL-17/IL-22).
- IL-12/IFN-γ axis defect = disseminated BCG, non-tuberculous mycobacteria and Salmonella.
- DOCK8 = hyper-IgE with severe viral skin infections and allergies.
- CARD9 = invasive fungal infections.

## 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.

## Memory aid

Picture a «cold STAT» patient: Cold abscesses, Staphylococcus, Teeth that never fall out, Atopic-looking eczema, Towering IgE. For IL-12/IFN-γ, BCG spreads everywhere when the macrophage never gets its orders.

## 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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## Related

- [Interleukin-17](https://durgical.com/en/immunology/interleukin-17/)
- [IL-12 and IL-23](https://durgical.com/en/immunology/il-12-and-il-23/)
- [Interferon-γ](https://durgical.com/en/immunology/interferon/)
- [Th1, Th2, Th17, Tfh and Treg](https://durgical.com/en/immunology/th1-th2-th17-tfh-and-treg/)
- [T-cell and combined deficiencies: DiGeorge, SCID, Wiskott–Aldrich, ataxia-telangiectasia](https://durgical.com/en/immunology/t-cell-and-combined-deficiencies-digeorge-scid-wiskott-aldrich-ataxia-telangiect/)
- [Immunodeficiency: warning signs and the infection pattern by defect](https://durgical.com/en/immunology/immunodeficiency-warning-signs-and-the-infection-pattern-by-defect/)
- [Phagocyte defects: CGD, LAD, Chédiak–Higashi](https://durgical.com/en/immunology/phagocyte-defects-cgd-lad-chediak-higashi/)
- [Immune tolerance and how autoimmunity begins](https://durgical.com/en/immunology/immune-tolerance-and-how-autoimmunity-begins/)

## Related conditions

- [Tuberculosis](https://durgical.com/en/conditions/tuberculosis/)
- [Vulvovaginal candidiasis](https://durgical.com/en/conditions/vulvovaginal-candidiasis/)

## Microorganisms

- [Candida albicans](https://durgical.com/en/microbiology/candida-albicans/)
- [Staphylococcus aureus](https://durgical.com/en/microbiology/staphylococcus-aureus/)
- [Mycobacterium tuberculosis](https://durgical.com/en/microbiology/mycobacterium-tuberculosis/)
- [Non-typhoidal Salmonella](https://durgical.com/en/microbiology/non-typhoidal-salmonella/)
- [Aspergillus fumigatus](https://durgical.com/en/microbiology/aspergillus-fumigatus/)

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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](https://medlineplus.gov/genetics/condition/autosomal-dominant-hyper-ige-syndrome/) (U.S. National Library of Medicine (MedlinePlus), 2026); [19.4 Immunodeficiency](https://openstax.org/books/microbiology/pages/19-4-immunodeficiency) (OpenStax (Microbiology), 2016); [21.5 The Immune Response against Pathogens](https://openstax.org/books/anatomy-and-physiology-2e/pages/21-5-the-immune-response-against-pathogens) (OpenStax (Anatomy and Physiology 2e), 2022).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/immunology/hyper-ige-syndrome-chronic-mucocutaneous-candidiasis-and-the-il-12-ifn-axis/