Primary Immunodeficiency Diseases – Combined T- and B-Cell Immune Deficiency
Primary immunodeficiency diseases (PIDs) are inherited disorders affecting
components of the immune system, leading to increased susceptibility to infections, autoimmunity, and malignancy.
Combined T- and B-cell deficiencies involve defects in both cellular (T cell–mediated) and humoral (B cell–mediated) immunity.
Key Features
- Severe, recurrent, or unusual infections (bacterial, viral, fungal, protozoal).
- Often present early in life (infancy).
- Failure to thrive, chronic diarrhea, persistent thrush.
Examples of Combined Immunodeficiencies
1 Severe Combined Immunodeficiency (SCID)
Etiology
- X-linked SCID (most common):
- Mutation in IL-2 receptor gamma chain (IL2RG gene) → defective cytokine signaling → impaired T cell and NK cell development.
- Autosomal recessive SCID:
- Adenosine deaminase (ADA) deficiency → toxic metabolite accumulation → lymphocyte death.
- RAG1/RAG2 mutations → failure of V(D)J recombination → no functional T or B cells.
Pathogenesis
- Severe deficiency of T cells → impaired cellular immunity.
- B cells may be present but non-functional due to lack of T cell help → defective humoral immunity.
- NK cell defects in some subtypes.
Clinical Features
- Recurrent severe infections: viral (CMV, RSV), fungal (Candida, Pneumocystis), bacterial (sepsis, otitis, pneumonia).
- Chronic diarrhea.
- Failure to thrive.
Diagnosis
- Lymphopenia (↓ T cells, often ↓ B and NK cells).
- Low immunoglobulin levels (hypogammaglobulinemia).
- Absent thymic shadow on chest X-ray (in T cell defects).
Treatment
- Isolation (protective environment).
- Prophylactic antimicrobials.
- Intravenous immunoglobulin (IVIG).
- Hematopoietic stem cell transplantation (HSCT) → curative.
- Gene therapy (for specific mutations, e.g., IL2RG).
3 Wiskott-Aldrich Syndrome (WAS)
Etiology
- X-linked mutation in WAS gene → defective cytoskeleton remodeling in immune cells.
Pathogenesis
- Impaired T and B cell function.
- Platelet dysfunction.
Clinical Triad
- Eczema.
- Recurrent infections.
- Thrombocytopenia (small platelets).
Treatment
- IVIG, antibiotics.
- Platelet transfusions if needed.
- HSCT (curative).