Clinical Immunology and Serology
Clinical Immunology and Serology tests antigen–antibody principles, immunoassay formats, autoantibody interpretation, allergy testing, and immunodeficiency evaluation. The exam focuses on test performance and interference, not only disease associations.
Core rules
- Sensitivity detects disease when present; specificity detects health when absent. Positive predictive value depends on prevalence, so a good test can have low PPV in a low-prevalence population.
- ELISA uses enzyme-labeled antibody and substrate; wash steps remove unbound conjugate. Indirect ELISA detects patient antibody; sandwich ELISA detects antigen.
- ANA is a screening test; anti-dsDNA and anti-Smith are more specific for systemic lupus erythematosus. Titers and patterns support, but do not replace, clinical diagnosis.
- Complement consumption lowers C3/C4 in active immune-complex disease. Total IgE is less useful than specific IgE for allergy.
- Prozone occurs with excess antibody; postzone occurs with excess antigen. Both can cause falsely low or negative results.
Worked example
A test has sensitivity 95%, specificity 90%, and prevalence 10%. In 1,000 people: 95 true positives and 90 false positives. PPV = 95 / (95 + 90) = 51.4%. Reasoning: even with high sensitivity, half of positives are false in a low-prevalence setting. NPV is high because most people are disease-free.
Traps
Rheumatoid factor can cause false-positive IgM assays. Heterophile antibodies interfere with sandwich immunoassays. Lipemia and hemolysis affect some platforms. Do not interpret a positive ANA as diagnostic of lupus. Repeat borderline results and use confirmatory testing.