see also:

• immunology
• intravenous immunoglobulin (IVIg)
• allergy and hypersensitivity reactions

• a group of “antibody” proteins which form the “humoral” immune system and are produced by B lymphocytes

• a type of immunoglobulin that protects against infections of the mucous membranes lining the mouth, airways, and digestive tract
• serum IgA levels may be raised due to:
  • pulmonary and gastrointestinal inflammatory diseases
  • some autoimmune conditions
  • liver disease
  • plasma cell disorders

• immunoglobulin generally associated with allergic reactions, and parasitic infections

• composed of two identical heavy (CH) chains and two identical light (L) chains
• usually have 2 identical antigen binding sites (on the Fab arms)
• the amino acid sequences of the various IgG subclasses are 90 to 95 percent homologous
• CH regions are encoded by C gene segments clustered on chromosome 14
• four subclasses: IgG1, IgG2, IgG3, and IgG4
• functional differences among the subclasses result from structural variation in both the Fc regions and the hinge regions
• IgG1 and IgG3 fix C1q most effectively, IgG2 weakly, and IgG4 not at all
• the Fc region is important in binding to phagocyte membrane Fc receptors and in initiating phagocytosis following “opsonization” of the target antigen by it being bound to IgG
• 60-70% of serum IgG is IgG1, 20-30% is IgG2, 5-8% is IgG3 and 1-4% is IgG4
• half-lives are ~ 21 days although IgG3 half-life is only ~9 days
• serum IgG levels may be raised due to:
  • chronic active infection or inflammation
  • in association with plasma cell disorders

• acute phase antibody response to an antigen
• raised serum IgM levels may be due to:
  • nonspecific marker of inflammation
  • can be associated with liver disease

• multiple myeloma
• benign monoclonal IgG paraproteinaemia
• hyper IgM syndrome
  • family of 5 genetic disorders characterised by relatively high IgM levels
  • causes increased risk of infections and usually have thrombocytopenia and neutropenia
• Wiskott-Aldrich syndrome
  • rare X-linked recessive disease characterized by eczema, thrombocytopenia, immune deficiency, and bloody diarrhoea
  • IgM levels are reduced, IgA and IgE are elevated, and IgG levels can be normal, reduced, or elevated
• hyper-IgE syndrome
  • causes eosinophilia, high levels of IgE, retained primary teeth, recurrent “cold” staphylococcal infections, recurrent candidial infections, unusual eczema-like skin rashes, severe lung infections that result in pneumatoceles
  • AD and AR forms; thought to be caused by abnormal neutrophil chemotaxis due to decreased production of interferon gamma by T lymphocytes
• raised IgG4 levels:
  • IgG4-related systemic disease (IgG4-RSD)
    • rare
    • autoimmune pancreatitis
    • sialadenitis and salivary gland enlargement
    • tumor-like swelling of involved organs
  • may also occur in:
    • atopic dermatitis
    • allergen immunotherapy
    • idiopathic membranous nephropathy
    • Loeffler’s syndrome, leiomyosarcoma, periarteritis nodosa, and mycosis fungoides
    • rheumatoid arthritis

• X-linked agammaglobulinemia
  • complete lack of circulating B cells; 1 in 100,000 male newborns; Dx usually after a history of recurrent infections, mostly in the respiratory tract, through childhood
• transient hypogammaglobulinemia of infancy
• IgA deficiency
  • mild illness, mostly asymptomatic but increased risk of infections such as sinusitis, chest infections and UTI
  • risk of anaphylaxis to blood transfusions or intravenous immunoglobulin due to the presence of IgA in these blood products
  • higher risk of developing autoimmune diseases in middle age
  • 1 in 300 people;
• IgG sub-class deficiencies
• isolated primary IgM deficiency
  • may be asymptomatic, but is also associated with recurrent infections, asthma, atopy, allergic rhinitis, Bloom's syndrome, coeliac disease, systemic lupus erythematosus (SLE) and malignancy
  • prevalence 0.03% of general population and 0.1% of hospitalised patients
• common variable immunodeficiency
  • group of over 150 primary immunodeficiencies
  • low levels of IgG, IgA and/or IgM
  • recurrent infections, may develop bronchiectasis, splenomegaly, lymphadenopathy
  • malabsorption, atrophic gastritis, inflammatory bowel disease (IBD), aphthous stomatitis, polyarthritis, candida infection in lungs,
• immunodeficiency–centromeric instability–facial anomalies syndrome (ICF) syndrome
  • very rare AR disorder; childhood infections; hypertelorism, low-set ears, epicanthal folds and macroglossia.