Table 1.
Monogenic IEI associated with atopic disease.
| Gene | Inheritance | Immune Manifestations | Atopic Manifestations |
|---|---|---|---|
| Disorders of barrier function | |||
| FLG | AR | Skin infections | A.D., FA, A.R., As, eos, high IgE |
| SPINK5 | AR | Skin infections | A.D., FA, A.R., As, eos, high IgE |
| CDSN | AR | Skin infections | A.D., FA, eos, high IgE |
| DSG1 | AR | Skin infections | A.D., FA, eos, high IgE |
| DSP | AR | Skin infections | A.D., FA, eos, high IgE |
| Cytoskeletal abnormalities | |||
| WAS | XL | CID | A.D., FA, eos, high IgE |
| WIP | AR | CID | A.D., FA, eos, high IgE |
| DOCK8 | AR | CID | A.D., FA, eos, high IgE |
| STK4 | AR | CID | A.D., FA, eos, high IgE |
| Aberrant TCR signaling | |||
| CARD11 | AR | CID, SCID | Eos, high IgE |
| BCL10 | AR | CID, SCID | Eos, high IgE |
| MALT1 | AR | CID, SCID | Eos, high IgE |
| CARMIL2 | AR | CID | Eos, high IgE |
| ZAP70 | AR | CID, SCID | Eos, high IgE |
| LAT | AR | CID, SCID | Eos, high IgE |
| Cytokine pathways | |||
| IL6RA | AR | Skin, lung infections | A.D., eos, high IgE |
| IL6ST | AR, AD | Skin, lung infections | A.D., eos, high IgE |
| STAT3 | AD | Skin, lung infections | A.D., eos, high IgE |
| ZNF341 | AR | Skin, lung infections | A.D., eos, high IgE |
| Decreased T-cell repertoire | |||
| Multiple genes presenting as Omenn syndrome | AR | Leaky SCID | Erythroderma, eos, high IgE |
| Regulatory T-cell defect | |||
| FOXP3 | XL | AI | A.D., FA, As, eos, high IgE |
| IL2RA | AR | CID, AI | A.D., FA, As, eos, high IgE |
| Innate cell effector mechanisms | |||
| PLCG2 | AD | CVID, AI, autoinflammatory | Temperature-sensitive mast cell degranulation |
A summary of causative genes, heritability, and major clinical features is presented. Table includes disorders of barrier function where infections and atopy overlap with IEI. Overlapping mechanisms are discussed further in the main text. AD, autosomal dominant; AR, autosomal recessive; XL, x-linked; CID, combined immune deficiency; SCID, severe combined immune deficiency; CVID, common variable immune deficiency; A.D., atopic dermatitis; eos, eosinophilia; AI, autoimmunity; A.R., allergic rhinitis; FA, food allergy; As, asthma.