Diagnostic tests for primary immunodeficiency disorders: Classic and genetic testing

Area of Science:

• Immunology
• Genetics
• Clinical Diagnostics

Background:

• Primary immunodeficiency diseases (PIDs) are genetic disorders compromising the immune system, leading to infections, autoimmunity, and malignancy.
• Over 500 PIDs are recognized, with increasing prevalence of secondary immunodeficiencies due to immunosuppressive therapies and medical advancements.
• Early diagnosis and management are vital to reduce infection risks and associated morbidity in patients with immune defects.

Purpose of the Study:

• To update clinicians on laboratory tests for evaluating immune system function in patients with primary immunodeficiency disorders.
• To provide a comprehensive overview of diagnostic testing options for PIDs, categorized by host defense components.

Main Methods:

• Clinical evaluation including medical history and physical examination to identify potential immune defects.
• Laboratory testing encompassing quantitative and functional assays (e.g., cell counts, immunoglobulin levels, antibody titers, lymphocyte subset enumeration).
• Genetic testing including Sanger sequencing and next-generation sequencing for unbiased genetic evaluation, supplemented by advanced research techniques.

Main Results:

• Laboratory evaluation is essential for diagnosing immunodeficiency disorders by assessing affected immune cells, functions, or products.
• A combination of classic laboratory tests and genetic analyses, including advanced techniques, is often required for definitive diagnosis.
• Testing strategies are organized based on the specific components of the host defense system being evaluated.

Conclusions:

• Accurate diagnosis of primary immunodeficiency diseases relies on a multi-faceted approach combining clinical assessment and diverse laboratory investigations.
• Comprehensive laboratory testing, from basic assays to advanced genetic analysis, is critical for timely and effective management of PIDs.
• This review provides clinicians with an updated guide to laboratory testing options for diagnosing and managing patients with immunodeficiency.