Table 2.
Summary of polygenic autoinflammatory diseases with a role for IL-1
| Disease | Genetic associations linked with phenotype | Presentation | Therapeutic targets |
|---|---|---|---|
| sJIA/AOSD | Class II HLA locus, HDAC9 (ref.172), LACC1/FAMIN173 | Fever, arthritis, arthralgia, evanescent rash | IL-1, IL-6, TNF, IL-18, IFN-γ |
| Schnitzler syndrome | NLRP3 (ref.48) | Chronic urticaria, fever, arthralgia, lymphadenopathy, bone pain, skeletal hyperostosis | IL-1, TNF |
| Gout | ADRB3, MTHFR, SLC22A11, SLC22A12, SLC2A9, SLC2A12, ABCG2, SLC17A1, SLC17A3, ALC16A9, GCKR, LRRC16A, PDZK1, R3HDMZ, RREB1, ALDH16A1 (ref.174), MAF175, URAT1 (ref.176) | Recurrent flares of inflammatory arthritis, chronic arthropathy, tophaceous deposits, uric acid nephrolithiasis | IL-1 |
| Recurrent pericarditis | MEFV177, HLA B14, DRB1*01, DQB1*0202 (ref.178) | Pleuritic chest pain, pericardial rub, ECG changes, pericardial effusion | IL-1 |
| CRMO | IL1RN95 | Recurrent fever, arthritis, multifocal bone inflammation | IL-1, TNF |
| Hidradenitis suppurativa | PSENEN, NCSTN, PSEN1 (ref.179) | Inflammatory nodules, sinus tracts and open comedones in intertriginous areas | TNF, IL-1 |
| PASH | MEFV, NOD2, NLRP3, IL1RN, PSTPIP1, PSMB8 (ref.180), NCSTN181 | HS lesions, pyoderma gangrenosum, acne | IL-1, IL-18 |
| PAPASH | PSTPIP1 (ref.182) | HS lesions, pyogenic sterile arthritis, pyoderma gangrenosum, acne | IL-1, TNF, IL-17A, IL-18 |
| PASS | Unknown | HS lesions, pyoderma gangrenosum, acne vulgaris, ankylosing spondylitis | IL-1, IL-18 |
| AHLE | CFI183 | Fever, neurological dysfunction, seizures, CSF pleocytosis | IL-1 |
| PFAPA | IL12A, STAT4, IL10, CCR1–CCR3 (ref.109), CARD8 (ref.184), ALPK1 (ref.185) | Recurrent fever with regular periodicity, aphthous stomatitis, exudative pharyngitis, cervical adenitis | IL-1 |
| Kawasaki disease | FCGR2A, BLK, CD40 (refs186,187), ITPKC, CASP3 (ref.188) | Fever, conjunctivitis, mucositis, rash, cervical lymphadenopathy, coronary artery dilatation | TNF, IL-1 |
| Behçet disease | IL12A, IL10, STAT4, CCR1–CCR3, IL23R–IL12RB2, FUT2 (refs109,189), HLAB51/B5 (ref.190) | Recurrent genital aphthae, uveitis or retinal vasculitis, nodular or papulopustular skin lesions, positive pathergy | IL-1, TNF |
AHLE, acute haemorrhagic leukoencephalitis; AOSD, adult onset Still disease; CNS, central nervous system; CRMO, chronic recurrent multifocal osteomyelitis; CSF, cerebrospinal fluid; ECG, electrocardiogram; HS, hidradenitis suppurativa; PAPASH, pyogenic arthritis, acne, pyoderma gangrenosum, and suppurative hidradenitis; PASH, pyoderma gangrenosum, acne, suppurative hidradenitis; PASS, pyoderma gangrenosum, acne and suppurative hidradenitis; PFAPA, periodic fever, aphthous stomatitis, pharyngitis, adenitis; sJIA, systemic juvenile idiopathic arthritis; TNF, tumour necrosis factor.