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Primary Immunodeficiencies

mLpenguin

• 2 min read
Primary Immunodeficiencies
Photo by National Institute of Allergy and Infectious Diseases / Unsplash

B-Cell

Selective IgA Deficiency

  • Most common primary immunodeficiency
  • Defect: B-cells fail to produce IgA
  • Presentation:
    • Asymptomatic (often)
    • Recurrent mucosal infections: sinopulmonary, GI (Giardia)
    • Anaphylaxis to blood products (anti-IgA antibodies)
    • ↑ risk of celiac disease, autoimmune disorders
  • Labs: ↓ IgA only, normal IgG/IgM
  • Treatment: Supportive; avoid IVIG (contains IgA, can trigger anaphylaxis)

Common Variable Immunodeficiency (CVID)

  • Defect: Impaired B-cell differentiation → ↓IgG, IgA, ± IgM
  • Presentation:
    • Recurrent sinopulmonary infections (Strep pneumo, H. flu)
    • Autoimmune diseases (RA, ITP)
    • GI: chronic diarrhea, Giardia
    • ↑ risk of lymphoma and bronchiectasis
  • Labs:
    • ↓ IgG + ↓ IgA and/or IgM
    • Normal B-cell count
      • X-linked agammaglobulinemia has decreased
  • Treatment: IVIG
Think CVID in an adult with recurrent respiratory infections, low immunoglobulins, and autoimmunity.

X-linked (Bruton) Agammaglobulinemia

  • Defect: BTK gene mutation → failure of B-cell maturation
  • Presentation:
    • Boys >6 months old
    • Recurrent bacterial infections (esp. encapsulated bugs)
    • Absent tonsils/lymphoid tissue
  • Labs:
    • ↓ B-cells (CD19+) - CVID has normal levels
      • ↓ all Ig levels
  • Diagnosis: Flow cytometry
  • Treatment: IVIG, avoid live vaccines
Male infant with infections and no tonsils - think Bruton.

T-Cell

Severe Combined Immunodeficiency (SCID)

  • Defect: Impaired T-cell development → combined T & B cell failure
    • IL-2Rγ chain defect (X-linked)
    • ADA deficiency (autosomal recessive)
  • Presentation (infancy):
    • Recurrent infections (bacterial, viral, fungal)
    • Chronic diarrhea
    • Failure to thrive
    • Absent thymic shadow
  • Labs:
    • ↓ T-cells, immunoglobulins
    • ↓/absent B-cell function
  • Treatment: Bone marrow transplant (urgent), avoid live vaccines
SCID the Bubble kid

Thymic-Parathyroid Dysplasia - DiGeorge Syndrome (22q11.2 Deletion)

  • Defect: Failure of 3rd/4th pharyngeal pouches → absent thymus/parathyroids
  • CATCH-22:
    • Cardiac defects (conotruncal: Tetralogy, truncus arteriosus)
    • Abnormal facies
    • Thymic hypoplasia (↓ T-cells)
    • Cleft palate
    • Hypocalcemia (tetany/seizures)
  • Labs:
    • ↓ T-cells, PTH, Ca++
    • Normal B-cell count
  • Diagnosis: FISH for 22q11.2
  • Treatment:
    • Calcium + vitamin D
    • Thymic transplant if severe
A neonate with seizures, murmur, and infections - think DiGeorge.

Hyper-IgM Syndrome

  • Defect in CD40 ligand (CD40L) on T cells (most common form; X-linked)
    • B cells can’t receive signals from T-helper cells → no isotype switching
  • Typically in infants or young children:
    • Recurrent sinopulmonary infections (e.g., Strep pneumo, H. flu)
  • Labs:
    • ↑ or normal IgM
    • ↓ ↓ ↓ IgG, IgA, IgE

Hyper-IgE Syndrome (Job Syndrome)

  • Defect: STAT3 mutation → impaired Th17 (T helper) cell development → impaired neutrophil chemotaxis
  • Presentation:
    • “Cold” abscesses (Staph)
    • Eczema
    • Coarse facies, retained teeth, fractures
  • Labs:
    • ↑ IgE, eosinophilia
  • Treatment: Antibiotics, supportive

Innate immune system

Wiskott-Aldrich Syndrome

  • Defect: WASp gene (X-linked) → defective cytoskeleton in WBCs and platelets
  • WATER
    • Wiskott/WAS protein
    • Aldrich
    • Thrombocytopenia (fewer and smaller platelets)
    • Eczema
    • Recurrent (pyogenic) infections
  • Labs:
    • ↓ platelets, ↓ IgM
    • ↑ IgA/IgE
  • Treatment: Bone marrow transplant
Think Wiskott in a boy with bleeding, eczema, and infections.

Chronic Granulomatous Disease (CGD)

  • Defect: NADPH oxidase deficiency → ↓ ROS
  • Presentation:
    • Recurrent catalase+ infections (Staph, Serratia, Aspergillus)
      • Recurrent pneumonia, lung abscesses, aspergillosis infection, skin abscesses, osteomyelitis, and chronic diarrhea.
    • Granuloma formation
  • Labs:
    • Abnormal DHR test (preferred)
    • Nitroblue tetrazolium (NBT) test (old)
  • Treatment: Prophylactic TMP-SMX + itraconazole ± IFN-γ

Leukocyte Adhesion Deficiency (LAD)

  • Defect: Integrin (CD18) defect → impaired neutrophil migration
  • Presentation:
    • Delayed umbilical cord separation
    • Recurrent infections, no pus
    • High neutrophil count in blood
  • Labs: ↑ neutrophils, but no neutrophils at infection site due to inability to migrate
  • Treatment: Bone marrow transplant
No pus, high WBC, delayed cord - classic LAD.