U01.02.032 Immunodeficiencies T-cell disorders

T-cell disorders are immunodeficiencies that impair cellular immunity, leading to a range of infections and syndromic presentations. Understanding these conditions is crucial for recognizing clinical patterns and diagnostic findings in Step 1.

Key T-Cell Disorders

1. Thymic Aplasia (22q11 Microdeletion)

Pathophysiology: Failure of the 3rd and 4th pharyngeal pouch development → absent thymus and parathyroids.
Syndromes:
- DiGeorge Syndrome: Thymic, parathyroid, and cardiac defects.
- Velocardiofacial Syndrome: Palate, facial, and cardiac defects.
Clinical Features (Mnemonic: CATCH-22):
- C: Cardiac defects (e.g., tetralogy of Fallot, truncus arteriosus).
- A: Abnormal facies.
- T: Thymic hypoplasia → T-cell deficiency → recurrent viral/fungal infections.
- C: Cleft palate.
- H: Hypocalcemia due to parathyroid aplasia → tetany.
Investigations:
- ↓ T cells, ↓ PTH, ↓ Ca²⁺.
- Absent thymic shadow on CXR.

2. IL-12 Receptor Deficiency

Pathophysiology: Impaired Th1 response; autosomal recessive inheritance.
Clinical Features:
- Disseminated mycobacterial and fungal infections.
- May present after BCG vaccine administration.
Investigations: ↓ IFN-γ levels.
Note: Most common cause of Mendelian susceptibility to mycobacterial diseases (MSMD).

3. Autosomal Dominant Hyper-IgE Syndrome (Job Syndrome)

Pathophysiology: STAT3 mutation → Th17 cell deficiency → impaired neutrophil recruitment.
Clinical Features (Mnemonic: ABCDEF’s to get a Job!):
- A: Cold (non-inflamed) staphylococcal Abscesses.
- B: Retained Baby teeth.
- C: Coarse Cacies.
- D: Dermatologic problems (eczema).
- E: Elevated Eosinophils and IgE.
- F: Bone Fractures from minor trauma.
Investigations: ↑ IgE, ↑ eosinophils.

4. Chronic Mucocutaneous Candidiasis

Pathophysiology: T-cell dysfunction leading to impaired immunity against Candida species.
Etiology:
- Classic form caused by AIRE gene defects.
Clinical Features:
- Persistent, noninvasive Candida albicans infections of skin and mucous membranes.
Investigations:
- Absent in vitro T-cell proliferation in response to Candida antigens.
- Absent cutaneous reaction to Candida antigens.

Summary Table

Disorder	Pathophysiology	Key Features	Investigations
Thymic Aplasia (DiGeorge)	22q11 microdeletion	CATCH-22, ↓ T cells, hypocalcemia, tetany	↓ T cells, ↓ PTH, ↓ Ca²⁺, CXR
IL-12 Receptor Deficiency	↓ Th1 response (AR)	Disseminated mycobacterial/fungal infections, ↓ IFN-γ	↓ IFN-γ
Hyper-IgE Syndrome (Job)	STAT3 mutation → ↓ Th17 cells	ABCDEF: abscesses, coarse facies, eczema, ↑ IgE/eosinophils	↑ IgE, ↑ eosinophils
Chronic Mucocutaneous Candidiasis	T-cell dysfunction	Persistent mucocutaneous Candida infections	Absent T-cell proliferation

Points to Remember

Mnemonic Alerts:
- Thymic Aplasia: CATCH-22.
- Job Syndrome: ABCDEF.
High-Yield Associations:
- BCG vaccine reaction → Think IL-12 receptor deficiency.
- Persistent Candida → Chronic mucocutaneous candidiasis.
Imaging Clue: Absent thymic shadow in DiGeorge syndrome.
Key Lab Findings:
- ↓ T cells in thymic aplasia.
- ↑ IgE in Job syndrome.

Prepare thoroughly to identify these patterns quickly during clinical vignettes in Step 1!

USMLE Step 1 Review Series

Curriculum