PID Overview - Immune System Gaps
- Primary Immunodeficiencies (PIDs): Genetic defects causing absent/impaired immune system components (e.g., B/T cells, phagocytes, complement).
- Hallmarks: ↑ susceptibility to infections (severe, recurrent), autoimmunity, and malignancy.
- Suspect with warning signs (📌 SPURT):
- Severe infections (e.g., requiring IV antibiotics)
- Persistent infections (slow to clear)
- Unusual pathogens or sites
- Recurrent infections (too frequent)
- Family History of PID or early deaths
⭐ Most PIDs present with recurrent infections; type of infection often points to specific immune defect.
B-Cell Deficiencies - Antibody Alarms
- Defective antibody production; recurrent sinopulmonary, GI infections.
- 📌 Mnemonic: Boys Totally Knockout Antibodies (BTK in XLA).
| Feature | XLA (Bruton's) | CVID | Selective IgA Deficiency |
|---|---|---|---|
| Onset | 6-18 mo | Bimodal | Any age |
| Ig Levels | All ↓ (IgG < 200 mg/dL) | IgG ↓, IgA/M var. ↓ | IgA ↓ (< 7 mg/dL), others normal |
| B-cells (CD19+) | Absent/↓ | Normal/↓ (poor func) | Normal |
| Gene | BTK | ICOS, TACI etc. | Multifactorial |
| Key Infections | Encapsulated bact, enteroviruses | Encapsulated bact, Giardia | Sinopulmonary, GI, Atopy |
T-Cell & Combined Defects - Cellular Chaos Crew
| Disorder | Gene/Locus | Immune Defect | Key Clinical Features | Mnemonic (📌) |
|---|---|---|---|---|
| DiGeorge Syndrome | 22q11.2 del | ↓ T-cells (thymic hypoplasia) | Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia | CATCH-22 |
| SCID | Various | ↓ T, B, NK cells (severe forms) | FTT, severe/opportunistic infections (PJP, Candida, viral), absent thymic shadow; CD3+ T-cells < 300/μL | - |
| Wiskott-Aldrich Syn. | WAS gene | ↓ T-cells, ↓ platelets; ↓ IgM, ↑ IgA, ↑ IgE | Eczema, thrombocytopenia (small platelets), recurrent infections (pyogenic, opportunistic) | WASP (Wiskott-Aldrich: Infections, Thrombocytopenia/small platelets, Eczema) |
| Ataxia-Telangiectasia | ATM gene | ↓ T & B cells; ↓ IgA, IgE, IgG2; ↑ radiosensitivity | Cerebellar ataxia, oculocutaneous telangiectasias, ↑ AFP, ↑ malignancy (lymphoma) | AT (Ataxia, Telangiectasias) |
Phagocyte & Complement Issues - Defense Line Breaches
- Phagocyte Defects:
Feature CGD LAD-1 Defect NADPH oxidase (↓$O_2^-$) CD18 (integrin $\beta_2$) Inheritance X-linked > AR AR Infections Catalase (+) (📌 S. aureus, Aspergillus, Serratia, Nocardia, Burkholderia) Recurrent non-purulent; delayed cord separation (>30 days) Diagnosis DHR test Flow cytometry (↓CD18) 
- Complement Deficiencies: (Screen: CH50)
- Early (C1-C4): ↑ SLE risk, pyogenic infections.
- C3: Severe pyogenic infections, glomerulonephritis.
- Terminal (C5-C9 MAC): Recurrent Neisseria.
⭐ CGD is caused by defective NADPH oxidase, leading to impaired superoxide production and susceptibility to catalase-positive organisms.
PID Diagnostics & Therapy - Code Blue & Cures
-
Diagnostic Pathway:
-
Core Management:
- IVIG/SCIG: For antibody deficiencies.
- Prophylaxis: Antimicrobials, antifungals.
- HSCT: Curative for severe forms (e.g., SCID, WAS).
- Gene Therapy: Emerging for specific PIDs.
- Enzyme replacement: e.g., ADA-SCID.
⭐ Hematopoietic Stem Cell Transplantation (HSCT) is curative for many severe PIDs, especially SCID.
High‑Yield Points - ⚡ Biggest Takeaways
- XLA: BTK defect, no B-cells, infections after 6 months.
- CVID: Commonest symptomatic PID, low IgG, IgA, recurrent infections, autoimmunity.
- DiGeorge (22q11.2): Thymic hypoplasia, T-cell defect, hypocalcemia, cardiac issues.
- SCID: Severe infections, absent thymic shadow, T & B cell defects (e.g., ADA, IL2RG).
- WAS: X-linked, Thrombocytopenia, Eczema, Recurrent infections (WATER mnemonic).
- CGD: NADPH oxidase defect, catalase-positive organism infections, abnormal DHR test.
- Ataxia-Telangiectasia: ATM gene, ataxia, telangiectasias, IgA deficiency, ↑AFP.
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