Immunology · Year 2 · from Immunology
Case 1: Bare Lymphocyte Syndrome Type II (MHC Class II Deficiency)
Patient Demographics
- Age: 14 months old
- Sex: Female
- Ethnicity: North African (Moroccan descent)
Chief Complaint
Recurrent respiratory infections and failure to thrive
History of Present Illness
A 14-month-old girl, whose parents immigrated from Morocco, is referred for immunological evaluation after multiple hospitalizations for respiratory infections. She has had persistent diarrhea since 6 months of age and has been diagnosed with Cryptosporidium infection. She has not gained weight appropriately and has fallen from the 50th percentile at birth to below the 3rd percentile.
Past Medical History
- Recurrent pneumonia (3 episodes since 6 months)
- Chronic diarrhea (Cryptosporidium parvum identified on stool testing)
- Oral candidiasis (persistent)
- Failure to thrive
Birth History
- Full-term, uncomplicated delivery in Morocco
- Newborn SCID screening: Not performed (unavailable)
Family History
- Parents are first cousins
- Older brother died at age 2 from "lung infection"
- One healthy older sister (age 5)
Physical Examination
- General: Thin, wasted infant
- Vital Signs: T 37.8C, HR 140, RR 35
- Growth: Weight <3rd percentile, Length 10th percentile
- HEENT: Oral thrush; tonsils present but small
- Lymphatics: Small palpable lymph nodes
- Lungs: Crackles bilateral bases
- Abdomen: Distended, hyperactive bowel sounds
Laboratory Workup
| Test | Result | Reference Range |
|---|---|---|
| WBC | 8,500/uL | 6,000-17,500/uL |
| Absolute lymphocyte count | 2,800/uL | 3,000-9,500/uL |
| CD4+ T cells | 150/uL | 1,600-4,000/uL |
| CD8+ T cells | 1,800/uL | 560-1,700/uL |
| CD4:CD8 ratio | 0.08 | 1.0-2.5 |
| CD19+ B cells | Normal | -- |
| IgG | 250 mg/dL | 345-1236 mg/dL |
| IgA | 15 mg/dL | 14-159 mg/dL |
| IgM | 85 mg/dL | 43-207 mg/dL |
| MHC class II expression | Absent on monocytes, B cells | Present |
| MHC class I expression | Normal | -- |
| CIITA gene | Homozygous mutation | Wild type |
| HIV | Negative | -- |
Clinical Image
Image showing severe malnutrition/failure to thrive pattern. Image source: Wikimedia Commons (https://commons.wikimedia.org/wiki/File:Starved_child.jpg). Public domain.
Diagnosis
Bare Lymphocyte Syndrome Type II (MHC Class II Deficiency) due to CIITA mutation.
Discussion
Bare Lymphocyte Syndrome Type II results from defects in transcription factors required for MHC class II expression. Four complementation groups have been identified, with mutations in CIITA, RFX5, RFXAP, or RFXANK:
Why is MHC class II deficiency so severe?
- MHC class II is required for CD4+ T cell development in the thymus (positive selection)
- Without MHC class II, CD4+ T cells cannot mature - resulting in profound CD4 deficiency
- CD4+ T cells are required for:
- B cell activation and antibody responses (hypogammaglobulinemia)
- Macrophage activation (susceptibility to intracellular pathogens)
- CTL development (impaired CD8 responses)
Clinical features:
- Combined immunodeficiency (affects both cellular and humoral immunity)
- Opportunistic infections (Cryptosporidium, Candida, PJP)
- Bacterial infections
- Progressive lung disease
- The inverted CD4:CD8 ratio (very low CD4, normal-high CD8) is characteristic
Why do B cells and lymphoid tissue develop?
- B cell development is MHC class II-independent
- Lymphoid organs form normally (unlike in some SCID variants)
- But B cells cannot receive T cell help, so antibody production is impaired
Epidemiology:
- More common in populations with consanguinity (North Africa, Middle East)
- Autosomal recessive inheritance
Treatment
- Hematopoietic stem cell transplantation: Only curative option
- IVIG: For antibody replacement
- PJP prophylaxis: TMP-SMX
- Aggressive infection treatment: Including Cryptosporidium (difficult to eradicate)
- Nutritional support: TPN if severe malabsorption
Prognosis: Without HSCT, most patients die in the first decade from infections.