Table 1.
Overview of monogenic forms of IBD associated with inflammasome dysregulation.
| Gene | Disease | Effect on IL-1β production | Effect of IL-1 blockade | References |
|---|---|---|---|---|
| ADAM17 | Neonatal inflammatory skin and bowel disease | not clear | n.a. | |
| BTK | X-linked agammaglobulinemia 1 | context-dependent | + (mouse) | (90, 91) |
| CASP8 | Caspase-8 deficiency | ↑ | n.a. | (92) |
| CYBA | Chronic granulomatous disease | ↑ | + | (78, 93) |
| CYBB | Chronic granulomatous disease | ↑ | + | (78, 93) |
| IKBKG | Anhidrotic X-linked ectodermal dysplasia and immunodeficiency | not clear | n.a. | |
| IL10/IL10RA/IL10RB | IL-10 (receptor) deficiency | ↑ | + | (94–96) |
| MEFV | Familial Mediterranean Fever | ↑ | + | (97–100) |
| MVK | Mevalonate kinase deficiency | ↑ | + | (38, 97, 101, 102) |
| NCF1 | Chronic granulomatous disease | ↑ | + | (78, 93) |
| NCF2 | Chronic granulomatous disease | ↑ | + | (78, 93) |
| NLRC4 | Autoinflammation with infantile enterocolitis | ↑ | IL-18 | (103–105) |
| PTEN | PTEN hamartoma tumor syndrome | ↓ | n.a. | (106) |
| RIPK1 | RIPK1 deficiency | ↑ | n.a. | (107, 108) |
| STAT1 | IPEX-like disease | not clear | n.a. | |
| TRIM22 | TRIM22 defect | ↓ | n.a. | (109) |
| WAS | Wiskott-Aldrich syndrome | ↑ | + | (110–112) |
| XIAP | X-linked lymphoproliferative syndrome 2 | ↑ | n.a. | (113–115) |
Alphabetical list of IBD candidate genes showing effects on IL-1β production as well as the therapeutic efficacy of IL-1 blockade in the corresponding disorder. If a robust phenotype on IL-1β production has been documented the effect is indicated by arrows (up: higher IL-1β production; down: lower IL-1β production). Beneficial effects of IL-1 blockade are indicated by a plus sign. For BTK deficiency, only mouse data are available. For NLRC4 mutations, IL-18 blockade was shown to be effective. N.a., not assessed.