Immunologic
for primary immunodeficiencies and inborn errors of immunity with gene panels and exome sequencing
System Profile
Yield Comparison
Clinical Dimensions
- Frequent or severe infections
- Autoimmunity
- Poor response to vaccines
- Unusual infection organisms
- Primary immunodeficiencies (B-, T-, NK-cell defects)
- Complement deficiencies
- Antibody deficiency disorders
- Immune dysregulation syndromes (IPEX)
- Absent tonsils/adenoids
- Chronic candidiasis
- Eczema with infections
- Recurrent skin abscesses
- Failure to thrive with infections
- Poor wound healing
- Recurrent or severe infections needing IV antibiotics
- Chronic thrush
- Chronic diarrhea with infections
- Autoimmune symptoms (thyroid, vitiligo, cytopenias)
- Low IgG/IgA/IgM
- Poor vaccine titers
- Abnormal lymphocyte subsets
- Low complement activity
- Eosinophilia or lymphopenia
- Chronic elevation of CRP/ESR
- CT chest showing absent thymus
- Bronchiectasis
- Chronic sinus opacification
- Lymphoid hypoplasia
- Absence of lymph nodes
- Vaccine response testing poor
- Lymphocyte proliferation impaired
- Complement assays low activity
- Mitogen testing abnormal
- Detailed immunophenotyping showing primary immunodeficiency
- IVIG/SCIG therapy
- Long-term prophylactic antibiotics
- Interferon-gamma in CGD
- Chronic immunosuppressants for immune dysregulation
- Severe vaccine reactions
- Recurrent allergic-like reactions to immunologic agents
- Hypersensitivity to IVIG
- Ports for IVIG or long-term IV antibiotics
- Biopsies for suspected immunodeficiency
- Thymus-related procedures
- Immunoglobulin infusion teaching
- Infection prevention counseling
- Emergency plans for severe immunodeficiencies
- Ports for IVIG or long-term IV antibiotics
- Infusion pumps for immune therapies
- Immunology and allergy/immunology clinics managing recurrent infections, IVIG
- Immunologist recommending genetic PIDD panel or exome
- Frequent infections
- Diagnosed immunodeficiencies
- Autoimmunity clusters (thyroiditis, vitiligo, celiac)
- Early sepsis or unusual infections in relatives
- No obvious malnutrition, homelessness, or unsafe living environment to explain frequent serious infections
- Appropriate vaccine access
- Absent thymic shadow on chest X-ray
- Recurrent neonatal infections
- Persistent thrush
- Abnormal newborn SCID screen (low TREC)
Red Flag Combinations
Clinical patterns that should prompt consideration of genetic testing
Low immunoglobulins + recurrent infections + poor vaccine response
Lymphopenia + opportunistic infections
Autoimmunity + cytopenias
Screening Decision Pathway
When to consider genetic testing for immunologic presentations
graph TD
START["Patient Presents with\nImmunologic Concerns"] --> SCREEN{"Screen for\nRed Flags"}
SCREEN --> RF1["Abnormal SCID screening low TRECs"]
SCREEN --> RF2["Vaccine response screens showing poor antibody for..."]
SCREEN --> RF3["Infection-risk screening tools positive"]
RF1 --> EVAL{"Multiple\nFlags Present?"}
RF2 --> EVAL{"Multiple\nFlags Present?"}
RF3 --> EVAL{"Multiple\nFlags Present?"}
EVAL -->|Yes| TEST["Order Genetic Testing\n(ES/GS)"]
EVAL -->|No| MONITOR["Continue Monitoring\nRe-evaluate if New Findings"]
TEST --> DX["Molecular Diagnosis\n15-79% yield"]
style TEST fill:#dcfce7,stroke:#16a34a,color:#14532d
style DX fill:#bbf7d0,stroke:#16a34a,color:#14532d
style MONITOR fill:#fef3c7,stroke:#d97706,color:#92400e
Screening Red Flags
Findings on routine screening that may indicate genetic etiology
- Abnormal SCID screening (low TRECs)
- Vaccine response screens showing poor antibody formation
- Infection-risk screening tools positive
Exome / Genome Sequencing Indications
Clinical scenarios supporting ES/GS as a diagnostic approach
- Primary immunodeficiency suspected clinically with nondiagnostic panel tests
- Multiple autoimmune conditions
- Complex immune dysregulation
- Severe vaccine failure
Key Evidence
Published studies supporting genetic testing for immunologic conditions
| Study | Year | Type | Sample | Yield | Key Finding |
|---|---|---|---|---|---|
| Very Early Onset Inflammatory Bowel Disease: An Integrated A... | 2018 | Review | None | None | VEO-IBD has high rate of monogenic etiology requiring integrated genomic and imm... |
| CARMIL2 Deficiency as a Cause of Very Early Onset Inflammato... | 2019 | Cohort | None | None | WES identified CARMIL2 deficiency as monogenic cause of VEO-IBD with combined im... |
| Diagnostic Yield of Next Generation Sequencing in Geneticall... | 2019 | Systematic Review | None | 15-79% | Systematic review: 15-79% diagnostic yield across 36 NGS studies in PID; higher ... |
| Whole Exome Sequencing Approach for the Diagnosis of Primary... | 2020 | Cohort | 106 | 70% | WES achieved 70% diagnostic yield in consanguineous PID population, highest amon... |
| Rapid Low-Cost Microarray-Based Genotyping for Genetic Scree... | 2020 | Cohort | None | 39% | 39% diagnostic yield for CNVs in 97 PID patients by CMA; 22q11.2 deletion most c... |
| NLRP3 Gain-of-Function Variant in Very Early Onset Inflammat... | 2020 | Cohort | None | None | WES discovered novel NLRP3 gain-of-function variant as cause of VEO-IBD with aut... |
| Next-Generation Sequencing Diagnostics of Primary Immunodefi... | 2021 | Review | None | 10-79% | Systematic review of NGS for PIDs shows average 29% diagnostic yield across stud... |
| Diagnostic Yield and Therapeutic Consequences of Targeted Ne... | 2022 | Cohort | None | 15.3% | 15.3% diagnostic rate in 294 sporadic PID patients by WES; novel variants in CTL... |
Updated: 2026-02-25
Curated by: human
Status: human reviewed