| Domain | Evidence-backed finding | Quantitative data | Suggested ontology terms | Evidence type / limitations |
|---|---|---:|---|---|
| Identity | Immunodeficiency 11B with atopic dermatitis, commonly called **CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS)** | **OMIM 617638**; **MONDO:0054697** | MONDO:0054697; HP:0002721 Immunodeficiency | Aggregated disease-resource and human genetic evidence; distinct from autosomal-recessive complete CARD11 deficiency (OMIM 615206) and gain-of-function BENTA (pqac-00000000, pqac-00000001) |
| Genetic cause | Heterozygous germline loss-of-function **CARD11** variants dominantly interfere with wild-type CARD11 signaling; inheritance is autosomal dominant, with de novo and familial cases | Literature review summarized **63 patients** across 25 families/case groups | CARD11; HGNC:16393; GO:0030154 cell differentiation | Human pedigrees plus in-vitro functional assays; penetrance is incomplete and expressivity highly variable (pqac-00000006, pqac-00000021) |
| Onset | Usually infantile or early-childhood onset; severe dermatitis is commonly the first manifestation | Mean onset **5.9 months** in a 10-person CADINS cohort; dermatitis was initial in **7/10 (70%)** | HP:0003593 Infantile onset; HP:0007354 Atopic dermatitis | Single-center cohort; ascertainment favored symptomatic pediatric index cases (pqac-00000011) |
| Atopic disease | Multisystem atopy includes dermatitis, asthma, food allergy, allergic rhinitis, and sometimes eosinophilic gastrointestinal disease | Any atopy **89%**; atopic dermatitis **73%** | HP:0001047 Atopic dermatitis; HP:0002099 Asthma; HP:0500093 Food allergy; HP:0004403 Allergic rhinitis | International-cohort summary; denominators and manifestations vary across reports (pqac-00000014, pqac-00000019) |
| Laboratory allergy phenotype | Elevated IgE and eosinophilia are common but not obligatory | Elevated IgE **75%**; persistent eosinophilia **8/10 (80%)** in one cohort | HP:0003212 Elevated serum IgE; HP:0001880 Eosinophilia | Cohort-level observations; values vary with age and treatment (pqac-00000011, pqac-00000019) |
| Infection susceptibility | Recurrent respiratory and viral cutaneous infections reflect variable combined or humoral immunodeficiency; bronchiectasis may develop | Respiratory/viral infections approximately **68%** | HP:0002205 Recurrent respiratory infections; HP:0004429 Recurrent viral infections; HP:0002110 Bronchiectasis | Human cohorts and case reports; pathogen-specific frequencies are unavailable (pqac-00000003, pqac-00000019) |
| Immune dysregulation | Autoimmunity, neutropenia, oral ulcers, and rare lymphoma broaden the phenotype beyond allergy | Autoimmunity approximately **20%**; neutropenia approximately **15%**; oral ulcers approximately **15%**; lymphoma **<10%** | HP:0002960 Autoimmunity; HP:0001875 Neutropenia; HP:0000155 Oral ulcer; HP:0002665 Lymphoma | Small heterogeneous cohorts; malignancy association remains uncertain and may be variant- or infection-dependent (pqac-00000019, pqac-00000023) |
| Immunologic testing | T- and B-cell counts may be normal, but antigen/mitogen proliferation and specific-antibody production can be impaired; IgG may be reduced | PHA proliferation impaired in **5/6** tested in one cohort; about half of another cohort required immunoglobulin replacement | HP:0032130 Abnormal lymphocyte proliferation; HP:0004315 Decreased circulating antibody level; HP:0004432 Abnormality of specific antibody response | Functional abnormalities are variable; normal lymphocyte subsets do not exclude CADINS (pqac-00000011, pqac-00000027, pqac-00000029) |
| Molecular mechanism | Mutant CARD11 poisons mixed oligomers, impairing scaffold opening and CARD11–BCL10–MALT1 signalosome assembly; this reduces antigen-receptor-induced canonical NF-κB and usually JNK/mTORC1 signaling, glutamine uptake, proliferation, and IFN-γ, while favoring IL-4/GATA3-associated T-helper-2 skewing | All validated dominant-negative variants in the cited cohort impaired TCR-induced NF-κB; mTORC1 effects were variable | GO:0038063 collagen-activated signaling pathway; GO:0043123 positive regulation of IκB kinase/NF-κB signaling; GO:0007254 JNK cascade; GO:0031929 TOR signaling; GO:0042092 type 2 immune response; CL:0000624 CD4-positive alpha-beta T cell | Human cells, transfected cell lines, and mechanistic synthesis; relative contribution of each pathway differs by variant (pqac-00000017, pqac-00000019, pqac-00000021, pqac-00000022) |
| Diagnosis | Suspect CADINS with very-early-onset or treatment-resistant atopy plus recurrent/unusual infections, poor vaccine responses, autoimmunity, or family history. Confirm a heterozygous CARD11 variant by panel/WES/WGS and segregation testing; functional demonstration of dominant interference is important for novel variants | A 2024 case used trio WES, Sanger validation, NF-κB reporter/co-immunoprecipitation, and RNA sequencing | NCIT:C17607 Genetic Testing; NCIT:C101295 Whole Exome Sequencing; HP:0000005 Mode of inheritance | No consensus disease-specific criteria; sequence variants may remain VUS without functional validation (pqac-00000005, pqac-00000006, pqac-00000022) |
| Treatment | Treat dermatitis conventionally; targeted IL-4/IL-13 blockade with dupilumab has produced marked benefit in case reports. Immunoglobulin replacement and antimicrobial prophylaxis are used for clinically significant antibody deficiency/infections. Glutamine partially rescued cellular defects in vitro but is not established clinical therapy | Dupilumab benefit reported at case level; no controlled response rate; immunoglobulin replacement reduced infections in one patient but did not prevent bronchiectasis | NCIT:C1576 Dupilumab; NCIT:C270 Immunoglobulin Therapy; NCIT:C1589 Tacrolimus; CHEBI:28300 glutamine | Observational reports and expert extrapolation; no disease-specific randomized trials, validated algorithm, or established HSCT indication for typical CADINS (pqac-00000009, pqac-00000025, pqac-00000026, pqac-00000030) |
| Prevention | Routine vaccination should be individualized after immune evaluation; HPV vaccination and surveillance have been proposed because HPV-positive carcinoma has occurred in affected families | HPV-positive squamous carcinoma reported in one family across the broader malignancy history | NCIT:C1746 HPV Vaccine; NCIT:C17139 Cancer Screening | Expert recommendation based on isolated familial malignancy observations, not prospective prevention studies (pqac-00000002, pqac-00000028) |
| R30W mouse model | Heterozygous **Card11 R30W/+** mice reproduce impaired T-, B-, and NK-cell signaling, reduced Treg numbers, reduced NK-cell IFN-γ, and age-dependent hyper-IgE, but not spontaneous dermatitis | Elevated IgE showed approximately **50% penetrance** and increased with age | CL:0000815 regulatory T cell; CL:0000623 natural killer cell; HP:0003212 Elevated serum IgE; GO:0032649 regulation of interferon-gamma production | Patient-variant knock-in model; failure to develop spontaneous dermatitis shows that high IgE alone is insufficient and limits direct phenotypic translation (pqac-00000017, pqac-00000021) |


*Table: Concise knowledge-base summary of IMD11B/CADINS identity, clinical frequencies, mechanism, diagnosis, management, and the Card11 R30W mouse model. Quantitative estimates derive from small, heterogeneous cohorts and should not be interpreted as population prevalence.*