Immunodeficiency and Immune Status Testing

Immunodeficiency and immune status testing is the laboratory evaluation of immune competence, used to investigate suspected primary (inborn) or secondary immune deficiency and to characterise immune status. It combines quantitative measures of antibodies and immune cells with functional assays of antibody responses, cellular function, and complement.

Definition

Immunodeficiency and immune status testing comprises laboratory assays that quantify and functionally assess components of the immune system to evaluate suspected immune deficiency and characterise immune competence.

Scope

The topic covers immunoglobulin and specific-antibody measurement, lymphocyte enumeration and subset analysis by flow cytometry, assessment of vaccine responses, and functional tests of phagocyte and complement activity. It is presented as a methodological and reference topic, not as a diagnostic or treatment protocol.

Core questions

• Which arm of the immune system (antibody, cellular, phagocytic, complement) does a given test interrogate?
• How do screening tests relate to confirmatory functional and genetic assays in evaluating inborn errors of immunity?
• How are age-specific reference intervals used when interpreting immune-cell and immunoglobulin measurements?

Key concepts

• Primary (inborn) versus secondary immunodeficiency
• Immunoglobulin and specific-antibody measurement
• Lymphocyte subsets and flow cytometry
• Vaccine (functional antibody) response testing
• Phagocyte function assays
• Age-specific reference intervals

Mechanisms

Evaluation typically layers screening and functional tests. Immunoglobulin classes and specific antibodies (for example, to vaccine antigens) assess humoral function; flow cytometry enumerates and phenotypes lymphocyte subsets to evaluate cellular immunity; functional assays such as the respiratory-burst test assess phagocyte function; and complement assays cover that pathway. Abnormal screening results are followed by confirmatory functional or genetic testing, and findings are interpreted against age-specific reference intervals because normal immune values change markedly with age.

Clinical relevance

This testing supports recognition and classification of immune deficiencies, which the International Union of Immunological Societies organises into categories of inborn errors of immunity, and informs the laboratory components of primary-immunodeficiency practice parameters. The entry describes how the assays work and how results are interpreted at a population level; it is not a basis for individual diagnostic or treatment decisions.

Epidemiology

Individual inborn errors of immunity are rare, but collectively they form a large and growing catalogue, with antibody deficiencies among the more frequently encountered categories. Secondary immune deficiency, arising from other illnesses or treatments, is more common and also prompts immune-status testing.

Evidence & guidelines

The field is guided by the IUIS classification of inborn errors of immunity and by practice parameters for the diagnosis of primary immunodeficiency, which set out a tiered laboratory approach from screening immunoglobulin and cell measurements to functional and genetic confirmation.

History

Laboratory immunodeficiency evaluation developed alongside the description of the first primary immunodeficiencies in the mid-twentieth century. Quantitative immunoglobulin assays, flow-cytometric lymphocyte phenotyping, and, more recently, genetic testing successively expanded the diagnostic toolkit, while international expert committees built and periodically updated a unifying classification.

Seminal works

• tangye-2022
• bonilla-2015

Frequently asked questions

What tests are used to evaluate suspected immune deficiency?

Evaluation commonly combines immunoglobulin and specific-antibody measurement, lymphocyte subset analysis by flow cytometry, and functional tests of phagocyte and complement activity, often followed by genetic testing.

Why are age-specific reference intervals important in immune testing?

Normal immunoglobulin levels and immune-cell counts change substantially with age, so results must be compared with age-matched reference ranges to be interpreted correctly.