Table 1.
Diseases classified as AiKDs, with their predisposing factors and mechanisms of pathogenesis (adopted and modified from References No. 17, 20, 22 and 26)
| Disease |
Genetic causative or predisposing factor |
Pathogenetic mechanism |
|---|---|---|
| Pustular psoriasis and related conditions | ||
| Generalized pustular psoriasis (GPP) (including impetigo herpetiformis) | 1) IL36RN loss-of-function variants |
a) hyperactivation of the IL-36 pathway |
| 2) CARD14 gain-of-function variants |
b) upregulation of CARD14-NFκB signaling | |
| 3) AP1S3 loss-of-function variants |
c) deficient AP1 endosomal translocation, defective autophagy | |
| 4) MPO loss-of-function variants |
d) hyperactivation of the IL-36 pathway, defective efferocytosis of neutrophils | |
| 5) SERPINA3 loss-of-function variants |
e) hyperactivation of the IL-36 pathway | |
| 6) BTN3A3 loss-of-function variant(s) |
f) disturbed IL-1/IL-36 axis (?), upregulation of the TNF-α pathway (?) | |
| acrodermatitis continua | 1) – 4) above | a) – d) above |
| palmoplantar pustular psoriasis (palmoplantar pustulosis) | 1) – 3) above | a) – c) above |
| Pityriasis rubra pilaris (PRP) (mainly type V) |
CARD14 gain-of-function variants |
upregulation of CARD14-NFκB signaling |
| Porokeratosis | loss-of-function variants in the mevalonate pathway-related genes MVK, MVD, PMVK and FDPS |
disturbed mevalonate-isoprenylated protein pathway |
| Hidradenitis suppurativa | 1) loss-of-function variants in the γ-secretase genes NCSTN, PSENEN and PSEN1 |
a) deficient γ-secretase, downregulated Notch signaling |
| 2) variants in NOD2, LPIN2, NLRP3, NLRP12, PSMB8, MVK, IL1RN |
b) other autoinflammatory pathways | |
| Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome | a single-nucleotide deletion in the 5′UTR of POMP (dysfunction of POMP) |
proteasome maturation deficiency, ER stress and UPR |
| Familial keratosis lichenoides chronica |
NLRP1 gain-of-function variants (unknown) |
hyperactivation of the NLRP1 inflammasome pathway |
| AiKD with EGFR deficiency |
EGFR loss-of-function variants |
hyperactivation of PLA2, NFκB, and JNK1 signaling |
| AiKD with hepatitis and autism |
JAK1 gain-of-function variants |
hyperactivation of JAK1-STAT signaling |