Table 1.
The International Union of Immunological Societies classification of primary immunodeficiencies. A few representative immunodeficiencies are listed in each category for illustrative purposes only. A comprehensive list of disorders is available in the 2019 IUIS publication [2]
| Category | Subcategory | Example |
|---|---|---|
| 1. Immunodeficiencies affecting cellular and humoral immunity | 1.a. SCID, defined by CD3 T cell lymphopenia | IL2RG |
| JAK-3 def | ||
| ADA def | ||
| RAG 1&2 def | ||
| 1.b. Combined immunodeficiencies generally less profound than SCID | DOCK8 def | |
| MHC I&II def* | ||
| CARD11 def | ||
|
CD40 ligand def (X-linked hyper IgM) | ||
| 2. Combined immunodeficiencies with associated or syndromic features | Wiskott-Aldrich | |
| Ataxia-telangiectasia | ||
| Chr22q11.2 deletion syndrome | ||
| 3. Predominantly antibody deficiencies | 3.a. Hypogammaglobulinemia | X-linked agammaglobulinemia |
| CVID | ||
| 3.b. Other antibody deficiencies | Selective IgA def | |
| Specific antibody def | ||
| 4. Diseases of immune dysregulation | 4.a. HLH & EBV susceptibility | |
| XLP 1&2 | ||
| Chediak Higashi | ||
| 4.b. Syndromes with autoimmunity and others | ALPS* | |
| APECED | ||
| IPEX | ||
| CTLA-4 deficiency | ||
| STAT3 GOF | ||
| 5. Congenital phagocyte defects | 5.a. Neutropenia (without anti-PMN) | Elastase def |
| Shwachman-Diamond | ||
| 5.b. Functional defects | LAD* | |
| CGD* | ||
| 6. Defects in intrinsic and innate immunity | 6.a. Bacterial and parasitic infections | STAT1 GOF |
| CARD9 | ||
| 6.b. Mycobacterial and viral | IFNGR1&2 | |
| WHIM | ||
| 7. Autoinflammatory disorders | Familial Mediterranean fever | |
| Mevalonate kinase def | ||
| Familial cold autoinflammatory syn | ||
| 8. Complement deficiencies | C5–C9 def (disseminated Neisserial infection) | |
| C1q,r,s (SLE-like syn) | ||
| Factor H&I def (atypical hemolytic uremic syn) | ||
| 9. Bone marrow failure | Fanconi anemia* | |
| Dyskeratosis congenita* | ||
| 10. Phenocopies of PID | Autoantibody to IL-17 or IL-22 (chronic mucocutaneous candidiasis) |
SCID severe combined immunodeficiency, CVID common variable immunodeficiency, HLH hemophagocytic lymphohistiocytosis, EBV Epstein-Barr virus, XLP X-linked lymphoproliferative disease, ALPS autoimmune lymphoproliferative syndrome, APECED autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy, IPEX immune dysregulation polyendocrinopathy enteropathy X-linked, LAD leukocyte adhesion deficiency, CGD chronic granulomatous disease, GOF gain of function, WHIM warts, hypogammaglobulinemia, infections, and myelokathexis, SLE systemic lupus erythematosus
*Multiple molecular causes exist for the condition