Definition

• Hypogammaglobulinemia: congenital or acquired decrease or absence in IgG classes

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Etiology

• Ataxia-Telangiectasia
• Autosomal Recessive Agammaglobulinemia (ARA)
• B-Cell Lineage Malignancies: increased catabolism of immunoglobulins
• Biallelic Deficiency of Mismatch Repair Protein PMS2
• Bruton Agammaglobulinemia (X-Linked Aggamglobulinemia) (see Bruton Agammaglobulinemia, [[Bruton Agammaglobulinemia]]): most cases do not present prior to 6 mo of age
• Common Variable Immunodeficiency (CVID) (see Common Variable Immunodeficiency, [[Common Variable Immunodeficiency]]): most cases do not present until the third or fourth decade of life
• Drug-Related Hypogammaglobulinemia: these cases probably occur in specific predisposed individuals
  • Captopril (see Captopril, [[Captopril]]): may cause IgA deficiency
  • Carbamazepine (Tegretol) (see Carbamazepine, [[Carbamazepine]]): may cause IgA deficiency or reversible hypogammaglobulinemia
  • Chlorpromazine (Thorazine) (see Chlorpromazine, [[Chlorpromazine]]): may cause IgA deficiency
  • Hydroxychloroquine (Plaquenil) (see Hydroxychloroquine, [[Hydroxychloroquine]]): may cause IgA deficiency
  • Lamotrigine (Lamictal) (see Lamotrigine, [[Lamotrigine]]): may cause reversible hypogammaglobulinemia
  • Penicillamine (see Penicillamine, [[Penicillamine]]): may cause IgA deficiency
  • Phenytoin (Dilantin) (see Phenytoin, [[Phenytoin]]): may cause IgA deficiency or reversible hypogammaglobulinemia
  • Sulfasalazine (see Sulfasalazine, [[Sulfasalazine]]): may cause IgA deficiency
  • Valproic Acid (Depakote, Depakene) (see Valproic Acid, [[Valproic Acid]]): may cause IgA deficiency
• Good Syndrome (Immunodeficiency with Thymoma) (see Thymoma, [[Thymoma]])
• Hyper-IgM Syndrome
  • CD40 Ligand (CD40L or CD154) Deficiency: this X-linked disorder is the etiology of most cases of Hyper-IgM syndrome
  • CD40 Deficiency
  • Activation-Induced Cytidine Deaminase (AID) Deficiency
  • Uracil-Nucleoside-Glycosylase (UNG) Deficiency
• Immunodeficiency–Centromeric Instability–Facial Anomalies (ICF) Syndrome: normal B-cell counts with agammaglobulinemia
• Jacobsen Syndrome (Hemizygous Deletion of Part of the Long Arm of Chromosome 11)
• Immunosuppression
  • Autologous Stem Cell Transplant (SCT) (see Bone Marrow Transplant, [[Bone Marrow Transplant]])
  • Chemotherapy
  • Corticosteroids (see Corticosteroids, [[Corticosteroids]])
    • Patients taking ≥12.5 mg prednisone for at least 1 year are at increased risk of hypogammaglobulinemia
    • Patients with hypogammaglobulinemia due to corticosteroid usually retain specific antibody responses: therefore, they are not usually candidates for immunoglobulin replacement therapy
  • Rituximab (see Anti-CD20 Therapy, [[Anti-CD20 Therapy]])
• Isolated IgA Deficiency (see Isolated IgA Deficiency, [[Isolated IgA Deficiency]]): few reported cases of bronchiectasis (although these were probably due to undetected IgG deficiencies): most common primary immunodeficiency syndrome (occurs in 1:600 persons)
• Lymphoproliferative Malignancy
  • Chronic Lymphocytic Leukemia (CLL) (see Chronic Lymphocytic Leukemia, [[Chronic Lymphocytic Leukemia]]): commonly associated with hypogammaglobulinemia and infection
  • Multiple Myeloma (see Multiple Myeloma, [[Multiple Myeloma]]): antibody deficiency with normal total IgG levels (due to contribution of the paraprotein to the total IgG level and due to tumor cells altering normal regulatory T cells, impairing B-cell maturation)
• Myelodysplastic Syndrome (see Myelodysplastic Syndrome, [[Myelodysplastic Syndrome]])
• Myotonic Dystrophy: increased catabolism of immunoglobulins
• Nephrotic Syndrome (see Nephrotic Syndrome, [[Nephrotic Syndrome]])
  • Hypoalbuminemia (see Hypoalbuminemia, [[Hypoalbuminemia]])
  • Edema: usually
• Prematurity in Infants: premature infants delivered before the third trimester usually lack adequate maternal immunoglobulin and may also more rapid metabolize the IgG that they have received
• Protein-Losing Enteropathy: intestinal lymphangiectasia, etc
  • IgG levels are typically affected more than IgM or IgA levels (however, the levels of IgG, IgM, and IgA may all be decreased in severe protein-losing enteropathy)
  • Hypoalbuminemia (see Hypoalbuminemia, [[Hypoalbuminemia]])
  • Edema: usually
• Selective IgG Subclass Deficiency (see Selective IgG Subclass Deficiency, [[Selective IgG Subclass Deficiency]]): decrease in one or more of the four classes of IgG with normal total IgG is most common type associated with bronchiectasis
• Severe Burns: increased catabolism of immunoglobulins
• Severe Combined Immunodeficiency (SCID)
• Specific Antibody Deficiency (SAD)/Specific Polysaccharide Antibody Deficiency (SPAD) (see Specific Antibody Deficiency, [[Specific Antibody Deficiency]]): poor serological response to polysaccharide antigens (with normal levels of immunoglobulins and IgG subclasses) and normal responses to protein antigens
• Steinert’s Disease
• Transcobalamine Deficiency
• Trisomy 18
• Wiskott-Aldrich Syndrome

(radiation, malnutrition, and thyrotoxicosis are not beleived to be associated with hypogammaglobulinemia)

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References

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