Immunodeficiency

Keywords: Hypogammaglobulinaemia

Causes

Appropriate Tests

 

Investigation for immunodeficiency should be considered in patients with severe or recurrent infection, infection with unusual organisms (eg, Pneumocystis carinii), or unexplained chronic diarrhoea - especially if there is a family history of similar problems or if other symptoms and signs suggesting immunodeficiency are present.

Initial testing includes Full blood count, White cell count differential, Blood film, Immunoglobulins G, A, M, Blood group (including 'reverse group') with isohaemagglutinin titres, Lymphocyte immunophenotyping.

See also Table 2.

Further specialised testing is indicated if clinical suspicion is high and/or abnormalities have been detected on initial testing.

Primary immunodeficiency states are far less common than secondary immunodeficiency.

See also Infection (increased susceptibility) and Opportunistic infections

Primary immunodeficiency

Molecular genetics may be of assistance - consult pathologist.

Antibody deficiency, especially

 

  • Common variable immunodeficiency

Lymphocyte immunophenotyping and surface markers - consult pathologist.

  • Transient hypogammaglobulinaemia of infancy

 

  • X-linked hypogammaglobulinaemia (Bruton)

 

  • Selective IgA deficiency

Immunoglobulin G subclass and specific antibody responses (eg, following pneumococcal vaccination) are indicated if there is a significant history of infection, Anti immunoglobulin A Ab.

  • IgG subclass deficiency

Immunoglobulin G subclass and specific antibody responses are indicated if there is a significant history of infection.

Cell mediated immunodeficiency, including

Measurement of cytokines following lymphocyte activation; Lymphocyte proliferative response - consult pathologist.

  • Di George syndrome (thymic aplasia)

Calcium, Phosphate, Albumin, Protein.

  • Chronic mucocutaneous candidiasis

Candidiasis.

Combined cell mediated and antibody deficiency, including

 

  • Severe combined immunodeficiency (SCID)

Molecular testing.

  • SCID with adenosine deaminase deficiency

Adenosine deaminase red cell.

  • Wiskott-Aldrich syndrome

Associated Eczema, Thrombocytopenia, Platelet disorders. Decreased IgM, increased IgA, IgE (see Immunoglobulins).

  • Ataxia telangiectasia

IgA levels are reduced.

Neutrophil defects, especially

  • Congenital neutropenia
  • Neutrophil dysfunction, especially
    • Chronic granulomatous disease
    • Myeloperoxidase deficiency
  • Lazy leucocyte syndrome
  • Job’s syndrome
  • Chediak-Higashi syndrome
  • Leucocyte adhesion deficiency

 


Neutrophil function studies.

 

 


Immunoglobulin E total.
Blood film, Platelet count, Platelet function test (aggregation/release studies).

Complement defects, especially

  • C1q, C4, C2 (SLE-like syndromes)
  • C3 (recurrent infections)
  • C5, C6, C7 or C8 (recurrent infections with Neisseria sp
  • C1 inhibitor deficiency

Complement CH50 or CH100 : if abnormal, individual complement components should be measured.

Secondary immunodeficiency

Secondary immunodeficiency may be due to a number of mechanisms in any one patient, including breach of the integument, antibody deficiency, cell mediated immune defects, neutrophil dysfunction, neutropenia.

Malignant disorders

 

Plasma cell myeloma

 

Chronic lymphocytic leukaemia

 

Hodgkin lymphoma

 

Hypoproteinaemic states

 

Malnutrition

 

Protein losing enteropathy, especially

 

  • Intestinal lymphangiectasia

May be associated with severe Lymphocytopenia.

Nephrotic syndrome

 

Following plasmapheresis

 

Iatrogenic, especially

 

  • Glucocorticoids

 

  • Cytotoxic drugs

 

  • Irradiation

 

Infection, especially

 

  • HIV infection

See also AIDS.

Metabolic, especially

 

  • Diabetes mellitus

 

  • Chronic renal failure

See Renal failure.

Others, including

 

  • Burns

 

  • Trauma

 

  • Surgery, anaesthesia

 

  • Extremes of age

 

  • Hyper IgM syndrome

Flow cytometry.