Table 1.
Relationship between psoriasis immunological mechanisms and susceptibility loci in different populations.
| Classification | Immunological | Psoriasis | Associated | Relationship | References |
|---|---|---|---|---|---|
| Mechanism/ | Susceptibility | population | |||
| Target | loci | ||||
| Autoantigens | LL-37 | HLA-C∗06:02 | European, Chinese | LL-37 binds to HLA-C∗06:02. Complexes with self-DNA to enhance plasmacytoid dendritic cell production of IFN-γ. | Lande et al., 2007, 2014; Mabuchi and Hirayama, 2016 |
| ADAMTSL5 | HLA-C∗06:02 | European, Chinese | Complexes with HLA-C∗06:02 and is presented to Va3S1/Vb13S1 TCR in CD8+ cytotoxic T cell. Induces production of IL-17A and IFN-γ. | Arakawa et al., 2015; Fuentes-Duculan et al., 2017 | |
| Antigen presentation | B27 | HLA-B∗27 | European | Misfolded or aberrant HLA-B27 molecules present self-peptides to CD8+ T cells. Accumulation in endoplasmic reticulum stimulates ER stress response pathways and the release of pro-inflammatory cytokines. | Ruiz et al., 2012; Colbert et al., 2014; Eder et al., 2017 |
| ERAP1 | ERAP1 haplotype (rs27524, rs26653, rs30187, rs151823) | European, Romanian, Han Chinese, Chinese Uygur | Modulates processing of MHC class I molecule and the binding of antigenic peptides to MHC molecule. | Strange et al., 2010; Sun et al., 2010; Lysell et al., 2013; Tang et al., 2014; Kenna et al., 2015; Popa et al., 2016 | |
| ERAP2 | ERAP2 haplotype (rs2248374, rs2910686) | European, Romanian | Modulates processing of MHC class I molecule and the binding of antigenic peptides to MHC molecule. | Popa et al., 2016 | |
| IL-20 Signaling | IL-20 | IL-20 HT GGA haplotype | North Indian | Upregulated IL-20 binds and induces STAT3 activation in keratinocytes, leading to an increase in cell proliferation and development of psoriatic lesions. | Lebre et al., 2012; Wani et al., 2018 |
| IL-17/23 Signaling | p40 subunit of IL-12 and IL-23 | IL-12B haplotype (A allele of rs3212227 and G allele of rs6887695) | European, Danish, Thai, Japanese | Increased expression of p40 subunit causes an increase of IFN-γ production, formation of IL-23 and biological activities of IL-12. Polarizes T cells to Th1 (by IL-12) and Th17 (by IL-23) lymphocytes. | Johnston et al., 2013; Zhu et al., 2013; Tamari et al., 2014; Zhao et al., 2016; Loft et al., 2018 |
| p19 subunit of IL-23 | IL-23A haplotypes | European, Chinese | Promotes survival and expansion of Th17 lymphocytes and the subsequent release of IL-17, IL-22 and TNF-α. Results in dysregulated IL-23 signaling. | Nair et al., 2009; Bowes et al., 2011; Chen G. et al., 2016; Tsoi et al., 2017 | |
| IL-17A | TRAF3IP2 | European, Japanese | IL-17A and IL-17F interacts with IL-17R recruits TRAF3IP2, a positive signaling adaptor protein required for activation of NF-κB signal transduction and T-cell immune response. | Ellinghaus et al., 2010; Tamari et al., 2014; Tsoi et al., 2015, 2017 | |
| PTTG1 | PTTG1 haplotype (rs2431697) | Han Chinese | The transcription factor coded by PTTG1 regulates proliferation and differentiation of keratinocyte. Overexpression of the gene results in hyperproliferation and impaired keratinocyte differentiation, as well as overproduction of TNF-α. | Sun et al., 2010; Ishitsuka et al., 2013 | |
| NF-κB Signaling | IκB-zeta | NFKBIZ | European | Transcriptional regulator of NF-κB which binds to the p50 subunit of NF-κB. Also required for IL-17 dependent signaling. Defective NFKBIZ also affects development of Th17 lymphocytes. | Tsoi et al., 2015 |
| ABIN-1 | TNIP1 haplotype (rs2233278) | European, Japanese, Chinese | ABIN-1 regulates NF-κB cascades through linking of A20 to NEMO/IKKγ, resulting in the A20-mediated deubiquitination of NEMO/IKKγ and the inhibition of NF-κB. Defective protein results in dysregulated NF-κB signaling. | Bowes et al., 2011; Callahan et al., 2013; Tamari et al., 2014; Tsoi et al., 2017 | |
| Skin Barrier | LCE3C and LCE3B proteins | LCE3C_LCE3B-del | Chinese, Mongolian, European | Absence of LCE proteins involved in repair of skin barrier injury leads to abnormal keratinocyte proliferation and differentiation, forming an imperfect epidermal barrier. | de Cid et al., 2009; Hüffmeier et al., 2009; Zhang et al., 2009; Riveira-Munoz et al., 2011; Xu et al., 2011 |
| LCE3D protein | LCE3D haplotype (rs512208, rs4112788, rs4085613) | Han Chinese, Mongolian | Higher expression of LCE3D results in abnormal formation of cornified envelope and dysregulation of terminal epidermal differentiation. | Jackson et al., 2005; Zhang et al., 2009; Bergboer et al., 2011; Tang et al., 2014; Sun et al., 2018 | |
| Miscellaneous | AIM2 | AIM2 haplotype (rs2276405) | Han Chinese | AIM2 binds cytosolic dsDNA, forming an inflammasome and activates caspase-1 and subsequently IL-1β in keratinocytes. | Dombrowski et al., 2011; Zuo et al., 2015 |
| MGAT5 | MGAT5 haplotype | European, Spanish | MGAT5 is required for N-glycosylation of asparagine residues in HLA molecules. Deficiency of MGAT5 enzyme and its activity reduces threshold for T cell activation, increases risk of losing immune tolerance and promotes triggering of autoimmune diseases. | Demetriou et al., 2001; Aterido et al., 2016 |