Which laboratory tests are most useful for the initial evaluation of suspected primary immunodeficiency?

For the initial evaluation of a suspected primary immunodeficiency (PID), the most useful laboratory tests include a full blood count with differential to assess lymphocyte and neutrophil numbers, quantitative serum immunoglobulin levels (IgG, IgA, IgM), and assessment of specific antibody responses to previous vaccinations or infections. Measurement of serum immunoglobulins helps identify hypogammaglobulinemia or dysgammaglobulinemia, which are common in many PIDs. Additionally, lymphocyte subset analysis by flow cytometry (including CD3, CD4, CD8, CD19, and NK cells) is important to evaluate T, B, and natural killer cell populations. Complement system screening tests, such as CH50 or AH50, may be indicated if complement deficiency is suspected. These initial tests provide a broad overview of immune function and guide further targeted investigations or genetic testing if needed ¹ (Tavakol et al., 2020; Raymond et al., 2022; Klangkalya et al., 2024).

Key initial tests:

• Full blood count with differential
• Serum immunoglobulin quantification (IgG, IgA, IgM)
• Specific antibody response assessment (e.g., pneumococcal, tetanus)
• Lymphocyte subset analysis by flow cytometry
• Complement function screening (CH50/AH50) if indicated

This approach aligns with UK clinical practice guidelines emphasizing immunoglobulin levels and lymphocyte phenotyping as first-line investigations, while recent literature supports the addition of functional antibody testing and complement assays to refine diagnosis and guide management ¹ (Tavakol et al., 2020; Raymond et al., 2022; Klangkalya et al., 2024).