IEI screening by clinical phenotype
Which initial immunology screen to send for each inborn-error-of-immunity presentation.
Evidence tier: Guideline-derived.
| Phenotype | First-line screen | Examples / next step |
|---|---|---|
| Recurrent sinopulmonary (encapsulated) infections | CBC + differential, IgG/IgA/IgM/IgE, vaccine titers (tetanus, diphtheria, pneumococcal) | Antibody deficiency (CVID, SAD, XLA, XLA: absent B cells/very low all Ig) |
| Recurrent / severe viral, fungal, opportunistic infection | Lymphocyte subsets (T/B/NK), HIV test, consider TREC/SCID newborn screen history | Combined / T-cell defect; SCID is an emergency in infants |
| Recurrent Neisseria / bacterial meningitis | CH50 (and AH50) | Terminal complement (C5–C9) or properdin deficiency |
| Recurrent abscesses, poor wound healing, delayed cord separation | CBC, neutrophil oxidative burst (DHR/NBT), CD11/CD18 | CGD (DHR), leukocyte adhesion deficiency |
| Immune dysregulation, autoimmunity, lymphoproliferation, granulomas, early IBD | Above + directed genetic panel / referral | CVID with complications, ALPS, IPEX, monogenic IBD |
| Eczema + recurrent infection + elevated IgE | IgE, lymphocyte subsets, directed genetics | Hyper-IgE (STAT3/DOCK8), Wiskott-Aldrich (low platelets, small platelet volume) |
Notes
- CH50 is normal complement screen; a near-zero CH50 with normal individual components suggests a terminal-pathway defect.
- Always interpret immunoglobulins against age-matched reference ranges; physiologic hypogammaglobulinemia of infancy is transient.
- Protective post-vaccination pneumococcal response (≥1.3 µg/mL or fold-rise) is the functional test for specific antibody deficiency.
Evidence & citations
- Orange JS, Chinen J, Horner CC, et al. 2025 Inborn errors of immunity practice parameter: guidance from the Joint Task Force on Practice Parameters, AAAAI, ACAAI and the Clinical Immunology Society. Ann Allergy Asthma Immunol. 2026;136(4):426-493.e1. PMID 41936423
- Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136(5):1186-1205.e78. PMID 26371839
Clinician decision support. Verify against the cited source. Not a substitute for clinical judgment. 100% on-device; no patient data is stored or transmitted.