immunoglobulins

introduction

a group of “antibody” proteins which form the “humoral” immune system and are produced by B lymphocytes - see adaptive immunity

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
it appears a protein, neuritin, prevents the over-production of IgE and thus allergies, anaphylaxis, asthma and many auto-immune conditions could be the result of a deficiency of neuritin according to researchers at the Australian National University (ANU) in 2021

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.