• Epidemiology
  1. Antibody or humoral or B-Cell Disorders account for Immunodeficiency in 78% of U.S. cases and 55% in Europe
  • Physiology
  • Pathophysiology
  1. Humoral Immunodeficiency presents after 3 months of age (when maternal antibodies are no longer present)
  2. B Cell deficiency or maturation defect results in Antibody deficiency
  3. Results in recurrent respiratory (ears, sinus, lungs) infections with encapsulated organisms
    1. Streptococcus Pneumoniae
    2. HaemophilusInfluenzae
  • Causes
  • No B-Cells: Agammaglobulinemia
  1. X-Linked Agammaglobulinemia or XLA (84% of Agammaglobulinemia cases in Europe)
    1. Bruton Tyrosine Kinase defect (Btk gene) results in defective B-Cell maturation
    2. Absent peripheral B-Cells results in very low serum IgG, IgA and IgM
    3. Infants may have no Tonsils or Lymph Nodes on exam
    4. Severe respiratory infections with Encapsulated Bacteria (e.g. Pneumococcus, H. Influenzae)
    5. Chronic Diarrhea (echoviruses and coxsackie virus), recurrent varicella
  1. IgG Subclass Deficiency of IgG2, IgG3, IgG4 (26% of U.S. cases)
  2. IgA Deficiency (30% of U.S. cases and most common B-Cell Disorder overall in U.S.)
    1. Low levels or absent IgA
    2. Prone to respiratory or gastrointestinal infections
    3. May be associated with IgG2 or IgG4 deficiency
  3. Common Variable Immunodeficiency or CVID (15% in U.S. and 46% in Europe of cases)
    1. Bimodal onset in preschool and in young adults
    2. Two Immunoglobulin subtypes are low (typically including Low total IgG, as well as IgM and IgA)
    3. B-Cells may be decreased in number and have defective function (T Cells may also be defective)
    4. Similar to X-Linked Agammaglobulinemia, but more mild
    5. Ear, sinus and lung infections occur as with other Antibody Disorders (e.g. Pneumococcus, H. Influenzae)
    6. CVID also present with malabsorption from Infectious Diarrhea
      1. Examples: C. difficile, Giardia, Salmonella, Campylobacter, Yersinia
  4. Transient Hypogammaglobulinemia of Infancy (3% of U.S. cases)
    1. Increased mild Bacterial respiratory infections
    2. Normal nadir that corrects by age 2-4 years
  1. Hyper-Immunoglobulin E (IgE) Syndrome (Job Syndrome)
    1. Significantly increased IgE levels
    2. Recurrent lung infections (staphylococcal empyema)
    3. Skin disorders (e.g. Eczema), infections and abscesses
      1. Cold lesions without the typical inflammatory changes of Skin Infections
      2. Eczematous Newborn Rash may be the first presenting finding
    4. Diagnosed with elevated serum IgE and gene analysis for STAT3 (Autosomal Dominant) and DOCK8
    5. Supportive care with infection treatment (e.g. Septra, Clindamycin, Cephalexin, Erythromycin, Doxycycline)
    6. Higher risk in HIV, Alcohol Use Disorder, Cystic Fibrosis, Diabetes Mellitus, prolonged Corticosteroids
    7. Freeman (2008) Immunol Allergy Clin North Am 28(2):277-91 +PMID: 18424333 [PubMed]
  2. Hyper-Immunoglobulin M or Hyper-IgM Syndrome (HIGM)
    1. CD40 Ligand deficiency (most common cause, X-Linked)
    2. T-Lymphocytes are unable to trigger B-Cells to switch Immunoglobulin production of IgM to IgG, IgA and IgE
    3. IgM levels increase, but other Antibody levels are deficient
    4. Results in recurrent and severe infections (including opportunistic infections)
    5. Results in increased malignancy risk
  • Resources
  1. National Primary Immunodeficiency Resource Center
    1. http://npi.jmfworld.org
  2. Immune Deficiency Foundation
    1. http://www.primaryimmune.org