What is the initial lab workup for immunology?

Initial Laboratory Workup for Immunology

The initial laboratory workup for immunology should include complete blood count with differential, quantitative immunoglobulins (IgG, IgA, IgM), vaccine response testing, lymphocyte subset analysis, and targeted testing based on clinical presentation. 1

Core Laboratory Tests

Humoral Immunity Assessment

• Complete Blood Count (CBC) with differential and peripheral blood smear 1, 2

  • Evaluates for cytopenias affecting multiple cell lines
  • Provides baseline hematologic parameters
  • Identifies abnormal cells

• Quantitative Immunoglobulins 1, 2

  • Measure serum IgG, IgA, and IgM levels
  • Consider IgG subclasses if indicated by clinical presentation
  • Particularly relevant in suspected antibody deficiencies

• Antibody Response Testing 1

  • Protein antigen response (tetanus, diphtheria)
  • Polysaccharide antigen response (pneumococcal)
  • Assess both pre- and post-vaccination titers
  • Response criteria vary by age (see below)

Cellular Immunity Assessment

• Lymphocyte subset analysis by flow cytometry 2

  • T cells (CD3+, CD4+, CD8+)
  • B cells (CD19+)
  • NK cells (CD16+/CD56+)
  • Age-specific reference ranges must be used

• Inflammatory markers 2

  • Erythrocyte sedimentation rate (ESR)
  • C-reactive protein (CRP)

Metabolic and Functional Assessment

• Comprehensive metabolic panel 2

  • Liver function (AST, ALT)
  • Kidney function (BUN, creatinine)
  • Electrolytes

• Additional markers 2

  • Lactate dehydrogenase (LDH)
  • Beta-2 microglobulin

Specialized Testing Based on Clinical Suspicion

Complement System Evaluation

• CH50 and AH50 assays 1
  • Screen for classical and alternative pathway defects
  • Interpretation guide:
    • Normal CH50/AH50: Normal complement function
    • Low AH50, normal CH50: Properdin defect
    • Zero AH50, normal CH50: Factor B or D defect
    • Low CH50, normal/low AH50: Regulatory component defect
    • Zero CH50, normal AH50: C1, C2, or C4 deficiency
    • Zero CH50, zero AH50: C3 or C5-C9 deficiency

Autoimmune Evaluation

• Autoantibody testing 1
  • ANA, SMA, anti-LKM-1, AMA, anti-LC1
  • Starting dilution 1:40 for adults, 1:20 for children
  • Use indirect immunofluorescence as primary screening method

Phagocyte Function

• Neutrophil oxidative burst assay 3
  • Evaluates NADPH oxidase function
  • Critical for diagnosing chronic granulomatous disease

Interpretation Guidelines

Antibody Response Interpretation

For pneumococcal polysaccharide responses 1:

• Age <6 years:

  • Mild: >1.3 mg/mL for >50% of serotypes with 2-fold increase for <50%
  • Moderate: >1.3 mg/mL for <50% of serotypes

• Age >6 years:

  • Mild: >1.3 mg/mL for >70% of serotypes with 2-fold increase for <70%
  • Moderate: >1.3 mg/mL for >70% of serotypes
  • Severe: >1.3 mg/mL for ≤2 serotypes

Immunoglobulin Level Interpretation

Patterns of abnormalities suggest specific diagnoses 1:

• Normal IgG, absent IgA, normal IgM: Selective IgA deficiency
• Low IgG, low IgA, normal/high IgM: Hyper-IgM syndrome
• Low IgG, low IgA, low IgM with normal B cells: Common Variable Immunodeficiency
• Absent all immunoglobulins with absent B cells: Agammaglobulinemia

Important Considerations

• Timing is crucial - Obtain tests before initiating immunosuppressive treatment 2
• Age-specific reference ranges must be used for all immunologic parameters 1
• Repeat testing may be necessary as autoantibody titers and specificity can vary during disease course 1
• Consider genetic testing for suspected monogenic disorders after initial screening tests 4
• Specialized reference laboratories should be utilized for complex immunologic testing 1

Common Pitfalls to Avoid

• Interpreting laboratory results in isolation without clinical context
• Failing to use age-appropriate reference ranges
• Not considering the effects of recent infections or medications on test results
• Relying on a single test rather than a pattern of abnormalities
• Overlooking the need for functional testing in addition to quantitative measurements
• Not repeating testing when clinical suspicion remains high despite normal initial results

This systematic approach to immunologic testing provides a framework for evaluating patients with suspected immunodeficiency while ensuring comprehensive assessment of all major immune components.