Initial Laboratory Workup for Immunocompromise
Begin with a complete blood count with differential, quantitative immunoglobulin levels (IgG, IgA, IgM, and IgG subclasses), and HIV testing as your foundational screening panel for any patient with suspected immunocompromise. 1
Core Initial Laboratory Tests
The essential first-tier workup includes:
Complete blood count with differential to assess for lymphopenia, neutropenia, or other cytopenias that suggest immune dysfunction 1
Quantitative serum immunoglobulins including IgG, IgA, IgM, and IgG subclasses to detect antibody deficiencies 1, 2
HIV testing as part of the foundational screening, given its prevalence and critical impact on management 1
Lymphocyte subset enumeration by flow cytometry to quantify CD4+ T cells, CD8+ T cells, B cells, and NK cells, which provides critical information about cellular immunity 1, 3
Vaccine-specific antibody titers to assess functional antibody responses, including tetanus, diphtheria, and pneumococcal serotypes 1, 2
Clinical Context-Driven Testing Strategy
Tailor your workup based on the infection pattern:
For recurrent sinopulmonary infections, prioritize immunoglobulin levels and vaccine responses first, as these patterns suggest antibody deficiency syndromes like common variable immunodeficiency or specific antibody deficiency 1
For opportunistic or severe viral infections, CD4+ T cell count becomes critical; counts <200 cells/mm³ indicate severe cellular immunodeficiency requiring immediate prophylaxis against opportunistic infections 1
Complement levels should be included in the initial workup when evaluating for primary immunodeficiency 2
Critical Interpretation Pitfalls to Avoid
Normal immunoglobulin levels do not exclude immunodeficiency—you must measure functional antibody responses to vaccines, as patients can have normal or even elevated total immunoglobulins but fail to produce specific protective antibodies 1
A normal total IgG does not exclude immunodeficiency; always measure IgG subclasses and functional antibody responses 1
For pneumococcal responses, protective levels are defined as concentration >1.3 mg/mL for >70% of serotypes tested in patients over 6 years old 1
If CNS infection is suspected in an immunocompromised patient, CSF findings are often misleadingly normal—CSF may be acellular despite active infection, so proceed with microbiological testing regardless of cell count 1