Immunology

Investigation of primary or secondary immunodeficiency

Immunodeficiency can be Primary (genetically determined) or Secondary (acquired)

There are many causes of secondary immunodeficiency, but most immunodeficiencies result from one or more of the following:

  • Acquired immunodeficiency (secondary to HIV infection)
  • Systemic disorders (e.g., diabetes, undernutrition,)
  • Lymphoproliferative disease (e.g., CLL, myeloma)
  • Immunosuppressive treatments (e.g., cytotoxic chemotherapy, bone marrow ablation before transplantation, radiation therapy)
  • Prolonged serious illness (particularly in patients who are critically ill, older, and/or hospitalised)

Primary immunodeficiencies (IEI – inborn errors of immunity) are classified by the main component of the immune system that is deficient, absent or defective:

  • Humoral immunity
  • Cellular immunity
  • Combined humoral and cellular immunity
  • Phagocytic cells (neutrophil defects)
  • Complement pathway defects
  • Other rare IEIs (e.g. autoinflammatory syndromes, DiGeorge’ syndrome, HIES)

Immunodeficiency often manifests as recurrent infections and should be suspected when infections are:

  • Severe
  • Persistent
  • Unusual
  • Recurrent
  • With or without Family history

 

Please note many of these tests have specific sample requirements and would need prior arrangement with the laboratory before requesting.

Suspected antibody (humoral) or cellular immunodeficiency

Tests offered:-

  • Immunoglobulin levelsand serum electrophoresis – assay performed and managed by Biochemistry Department (proteins section)
  • Functional antibodies: Functional antibody testing is done to evaluate vaccine responses in the investigation of suspected antibody deficiency (pre- and post-vaccine samples). These are second line investigations and must not be requested without documented low immunoglobulin levels and history of recurrent bacterial infections.

If there is strong clinical suspicion of antibody deficiency but normal immunoglobulin levels, then please discuss with Clinical Immunology Team prior to requesting functional antibody tests.

Tests offered are as listed below

  • HiB
  • Tetanus
  • Pneumococcal capsular polysaccharide (PCP)
  • Pneumococcal serotypes (in Prevenar vaccinated children and young adults)

(Please refer to Immunology laboratory handbook (insert page number) for further guidance regarding interpretation of results)

  • Lymphocyte subset analysis (EDTA sample – Mon-Thursday)

Tested using flow cytometry for enumerating the percentages and absolute cell counts of lymphocyte subsets in whole blood. Used for the diagnosis of different Inborn Errors of Immunity (IEIs) and for evaluation of cellular immune status (CD4/CD8 count) and monitoring of patients with HIV infection before and during antiviral treatment.

  • T cells (CD3+, CD4+ helper, CD8+ cytotoxic)
  • B cells (CD19+)
  • Natural Killer (NK) cells (CD16+/CD56+)
  • B cell phenotyping (including class-switched memory B cells) only to be requested with discussion and approval from Clinical Immunologists.

 

Suspected neutrophil defects

Chronic Granulomatous Disease (CGD) – Rare immunodeficiency affecting neutrophil functions and presenting typically within the first few years of life. Infections with catalase -positive organisms (Staph. aureus, Aspergillus, nocardia, & Serratia), deep seated abscesses, osteomyelitis and chronic granulomata are the hallmark of this disease

Tests offered:-

  • DHR (oxidative respiratory burst) neutrophil function: A flow cytometric assay can detect whether oxygen radicals are produced during phagocytosis; no production is characteristic of chronic granulomatous disease.

Must have prior arrangement with the laboratory due to stringent sample requirements. A control sample from a healthy individual MUST be supplied together with the patient’s sample. Samples must be urgently transported to the laboratory.

 

Hereditary or acquired angioedema – both conditions can present with unexplained episodes of peripheral, facial or abdominal angioedema (typically presents as ‘acute abdomen’)

Hereditary angioedema (HAE)

  • C3/C4 levels
  • C1 esterase inhibitor quantitative
  • C1 esterase inhibitor functional – Discuss with lab prior to request for sample specification.

Acquired angioedema

  • Anti C1q antibodies (in addition to above investigations)

 

Suspected Complement pathway defects

When to suspect

  • Recurrent meningitis with capsular organisms
  • Recurrent severe infections with capsular organisms
  • Family history of complement pathway defects

Initial investigations

  • C3 and C4 levels

Please discuss with Clinical Immunologists if strong clinical suspicion of complement pathway defects

Specialist tests offered include

  • Functional test for Classical complement pathway
  • Functional tests for alternate complement pathway
  • MBL studies
  • Relevant individual complements (if available) / appropriate genetic tests (R 15)