What are Primary Immunodeficiencies (PID)?
What are Primary Immunodeficiencies (PID)?
Primary Immunodeficiencies (PID), also known as Inborn Errors of Immunity (IBD), are a heterogeneous group of more than 450 genetic diseases that affect the development and/or function of the immune system.
This predisposes individuals to increased susceptibility to infections, but can also manifest as autoimmunity, chronic inflammation, severe allergies, and an increased risk of certain types of cancer.
Key point: Not all PIDs present with severe, recurrent infections. Immune dysregulation (autoimmunity, inflammation) is an increasingly recognized manifestation.
Sequential Diagnostic Approach
Sequential Diagnostic Approach
Step 1: Clinical Suspicion (The 10 Warning Signs)
≥4 otitis media in 1 year.
≥2 severe sinusitis in 1 year.
≥2 months on antibiotics with little improvement.
≥2 pneumonias in 1 year.
Failure to thrive or poor growth.
Recurrent skin or deep organ abscesses.
Persistent oral or cutaneous candidiasis (>1 year of age).
Need for IV antibiotics to treat infections.
≥2 invasive infections (sepsis, meningitis).
Family history of PID.
Step 2: Initial Laboratory Studies
| Proof | What to look for | Oriented Suspicion |
|---|---|---|
| Complete blood count with formula and platelet count | Lymphopenia, neutropenia, thrombocytopenia. | T Cell Defects, Phagocytic, Complex Syndromes. |
| Quantification of Immunoglobulins (IgG, IgA, IgM) | Low levels for age. | Humoral defects (Antibodies). |
| Serologies (Response to vaccines) | Low post-vaccination titers (e.g. tetanus, pneumococcus). | Antibody functional defects. |
| Complement Tests (CH50, AP50) | Low or absent levels. | Complement deficiencies. |
Step 3: Advanced Studies (In a specialized center)
If the initial studies are abnormal or the clinical suspicion is very high, the patient should be referred to the clinical immunologist for more in-depth studies:
- Lymphocyte subpopulations by flow cytometry: Count of T (CD3, CD4, CD8), B (CD19/CD20) and NK (CD16/56) lymphocytes.
- Lymphocyte proliferation tests: Evaluates the function of T lymphocytes.
- Phagocytic function studies (DHR Test): For Chronic Granulomatous Disease.
- Genetic studies: Next generation sequencing (NGS) to identify the causal mutation.
Therapeutic Options
Therapeutic Options
1. Immunoglobulin Replacement Therapy (IVIG / SCIG)
Cornerstone for antibody defects. Provides protective antibodies from healthy donors. It can be administered intravenously (IVIG) or subcutaneously (SCIG).
2. Antimicrobial Prophylaxis
Continuous use of antibiotics, antifungals, or antivirals to prevent infections in high-risk patients.
3. Immunomodulators
Drugs such as cytokines (Interferon-gamma) or inhibitors (e.g. JAK inhibitors) to control immune dysregulation and improve the function of specific cells.
4. Hematopoietic Stem Cell Transplantation (HSCT)
The only curative option for the most severe PIDs (e.g. Severe Combined Immunodeficiency - SCID). It replaces the patient's defective immune system with that of a healthy donor.
5. Gene Therapy
A rapidly evolving field that seeks to correct the underlying genetic defect in the patient's own cells. Approved for some forms of SCID.
When to Refer to Other Specialties
When to Refer to Other Specialties
The management of PID is multidisciplinary. It should be sent to Clinical Immunologist in case of any well-founded suspicion or abnormal laboratory finding. Other important referrals include:
- Gastroenterology: Due to chronic diarrhea, early-onset inflammatory bowel disease.
- Pulmonology: Due to bronchiectasis, interstitial lung disease.
- Rheumatology: Due to arthritis, autoimmune cytopenias, vasculitis.
- Hematology/Oncology: Due to severe cytopenias, lymphomas or other neoplasms.
- Clinical Genetics: For family genetic counseling.
Recommendations for Parents and Caregivers
Recommendations for Parents and Caregivers
TO DO
- Maintain strict hand hygiene (child and caregivers).
- Ensure good nutritional status.
- Consult immediately in case of fever or signs of infection.
- Inform the school about the child's condition and necessary precautions.
- Rigorously comply with prophylactic and replacement treatments.
- Seek psychological support for the child and family if necessary.
WHAT NOT TO DO
- Administer live virus vaccines (Oral Polio, MMR, Varicella, Rotavirus) without the express authorization of the immunologist.
- Expose the child to crowds or people with active infections.
- Consume non-potable water or raw/undercooked foods.
- Minimize fever or "wait and see how it progresses."
- Allow contact with soil or stagnant water (risk of fungi/bacteria).
- Stop medication without medical indication.
Final Evaluation: Test your knowledge!
Final Evaluation: Test your knowledge!
Bibliography and Resources
Bibliography and Resources
- Bousfiha, A., et al. (2022). The 2022 IUIS-classification of Inborn Errors of Immunity. Journal of Clinical Immunology.
- Jeffrey Modell Foundation. (2024). 10 Warning Signs of Primary Immunodeficiency. Available in: info4pi.org
- European Society for Immunodeficiencies (ESID). (2024). Diagnostic Criteria and Guidelines. Available in: esid.org
- Picard, C., et al. (2018). International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity. Journal of Clinical Immunology.