Table 1.
Monogenic defects associated with autoimmunity and CVID.
| Genetic defect | Protein | Immune dysregulation | Targeted treatment | Non-targeted treatment |
|---|---|---|---|---|
| TNFRSF13B mutation | TACI defect | Variable phenotype. Single mutation considered risk factor for CVID; also found in asymptomatic individuals | Steroids, high dose immunoglobulin, rituximab, thrombopoeitin receptor agonist | |
| TNFRSF13C mutation | BAFF-R defect | |||
| 1-3 ICOS LOF | ICOS deficiency | Autoimmune enteropathy, cytopenias, rheumatic disease | ||
| NFKB1 LOF | NF-κB1 deficiency | Autoimmune cytopenias and enteropathy, lymphoproliferation, lymphoma | ||
| NFKB2 LOF | NF-κB2 deficiency | Pituitary hormone deficiencies, autoimmune disease affecting skin, hair and nails | ||
| 1-4 LRBA LOF | LRBA deficiency | Severe early-onset autoimmune disease (including autoimmune cytopenias, IBD, type 1 diabetes), lymphoproliferation, atopy (food allergy, dermatitis, urticaria) | Abatacept | |
| CTLA4 LOF | CTLA-4 deficiency | |||
| 1-4 PIK3CD GOF | PI3Kδ hyperactivity | Autoimmune cytopenias, primary sclerosing cholangitis, IBD, lymphoproliferation, lymphoma | Rapamycin; Leniolisib* | |
| 1-4 STAT3 GOF | STAT3 hyperactivity | Early onset endocrine autoimmunity (type 1 diabetes, hypothyroidism), autoimmune cytopenias, lymphoproliferation, interstitial lung disease | Tocilizumab; Jakinibs |
*
Currently in phase 3 clinical trial.