Immunology · Year 2 · from Immunology
Case 3: TAP Deficiency (Bare Lymphocyte Syndrome Type I)
Patient Demographics
- Age: 16 years old
- Sex: Female
- Ethnicity: Turkish descent
Chief Complaint
Recurrent sinopulmonary infections and chronic skin ulcers
History of Present Illness
A 16-year-old girl of Turkish descent with a history of recurrent sinusitis and bronchiectasis presents for evaluation. She has had pneumonia yearly since age 5 and developed bronchiectasis by age 10. She also has chronic, non-healing skin ulcers on her lower legs that have been present for years and biopsied multiple times without a clear diagnosis. She has never had opportunistic infections.
Past Medical History
- Recurrent sinusitis (5-6 episodes/year)
- Recurrent pneumonia (at least once yearly)
- Bronchiectasis (diagnosed at age 10)
- Chronic skin ulcers on lower extremities (since age 8)
- No history of viral infections, opportunistic infections
Family History
- Parents are second cousins
- Older brother with similar respiratory infections and skin lesions
Physical Examination
- General: Thin but overall well-appearing teenager
- Vital Signs: Normal
- HEENT: Nasal mucosal edema; bilateral TM scarring from prior infections
- Lungs: Scattered crackles; clubbing of fingers
- Skin: Multiple chronic granulomatous ulcers on both lower legs with raised borders
- Lymphatics: Normal
Laboratory Workup
| Test | Result | Reference Range |
|---|---|---|
| WBC | 9,500/uL | 4,500-13,500/uL |
| CD8+ T cells | Markedly reduced | -- |
| CD4+ T cells | Normal | -- |
| NK cells | Normal | -- |
| IgG | 850 mg/dL | 700-1600 mg/dL |
| IgA | 180 mg/dL | 70-400 mg/dL |
| MHC class I expression | <10% of normal | Normal |
| MHC class II expression | Normal | -- |
| TAP1 gene | Homozygous mutation | Wild type |
| Skin biopsy | Granulomatous inflammation with giant cells | -- |
| Chest CT | Bronchiectasis with tree-in-bud opacities | Normal |
Clinical Image
Image showing granulomatous inflammation pattern similar to that seen in TAP deficiency skin lesions. Image source: Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Granuloma_annulare_-_very_high_mag.jpg). Public domain.
Diagnosis
TAP Deficiency (Bare Lymphocyte Syndrome Type I/MHC Class I Deficiency) due to TAP1 mutation.
Discussion
TAP (Transporter Associated with Antigen Processing) deficiency is a rare form of MHC class I deficiency:
Normal TAP function:
- TAP1 and TAP2 form a heterodimeric transporter
- TAP transports cytosolic peptides into the ER for loading onto MHC class I molecules
- Without TAP, MHC class I molecules cannot be loaded with peptides and are unstable
- Result: Markedly reduced MHC class I surface expression
Why is the phenotype milder than MHC class II deficiency?
- MHC class I is not required for CD8+ T cell development in the thymus (surprising!)
- CD8+ T cells can develop but are functionally impaired in the periphery
- NK cells are present and functional
- The syndrome is primarily characterized by respiratory tract infections, not opportunistic infections
Characteristic clinical features:
- Recurrent bacterial sinopulmonary infections (not opportunistic)
- Bronchiectasis (progressive lung damage)
- Necrotizing granulomatous skin lesions on legs - very characteristic
- Generally survive to adulthood (unlike BLS Type II)
- NO severe viral infections (NK cells provide some antiviral defense)
Why granulomatous skin lesions?
- Mechanism unclear; may represent abnormal inflammatory response
- Pathognomonic for TAP deficiency when combined with respiratory infections
Treatment
- Prophylactic antibiotics: To reduce sinopulmonary infections
- Aggressive treatment of infections: Prevent progression of bronchiectasis
- Pulmonary rehabilitation: Airway clearance techniques
- Skin lesion management: Often refractory; may respond to topical steroids, calcineurin inhibitors
- HSCT: Has been performed in severe cases, but outcomes are variable
- Immunoglobulin replacement: Generally not indicated (antibody production intact)
- Surveillance: Monitor for lung function decline