And it is interesting that a missense mutation in SPRED1 and a splice region mutation in C3 are found in the psoriasis individuals in the other two MZ twin pairs without carrying HLA-C*0602 allele.
The frequency of HLA-C*0602 allele (4.1%) was lower than in patients with plaque-type psoriasis (4.1 vs. 16.3%, corrected p value [P<sub>c</sub>] = 0.02) and similar to that in the healthy population in Taiwan.
We sought to test whether HLA-C*06:02, the primary genetic susceptibility allele for psoriasis, predisposes patients to respond differently to the 2 most commonly prescribed biologics for psoriasis: adalimumab (anti-TNF-α) and ustekinumab (anti-IL-12/23).
Studies were included if they reported the association between HLA-C*06:02 status and 75% improvement in Psoriasis Area and Severity Index (PASI75) response to ustekinumab therapy in patients with plaque psoriasis after 6 and/or 3 months of treatment.
This includes the association of psoriasis with certain MHC (HLA) alleles, oligoclonal expansion of T cells in some cases, therapeutic response to T cell-directed immunomodulation, the onset of psoriasis following bone marrow transplantation, or induction of psoriasis-like inflammation by T cells in experimental animals.
Regression analysis showed that the LoPsA group at presentation was characterized by: less males (OR 0.4, p = 0.001), less HLA-C*06 (OR 0.3, p = 0.005), longer psoriasis duration (OR 1.04, p = 0.0005), higher BMI (OR 1.1, p = 0.005) and higher modified Steinbrocker score (mSS) (OR 1.1, p = 0.005).
An ERAP1 haplotype known to possess high enzymatic activity was associated with psoriasis if HLA-C*06:02 was present and a functional ERAP2 allele was absent.
The unbiased analysis of a paradigmatic Vα3S1/Vβ13S1-T-cell receptor from a pathogenic epidermal CD8<sup>+</sup> T-cell clone of an <i>HLA-C*06:02</i><sup>+</sup> psoriasis patient had revealed that HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation, and it identified a peptide form ADAMTS-like protein 5 as an HLA-C*06:02-presented melanocyte autoantigen.
Additionally, we showed a HLA-C*06:02-independent gender-related effect of the rs887466A allele which was protective against psoriasis in males (OR = 0.61, p = 9.2e-005), but not in females (p = 0.66).
Further analysis with imputed classical HLA alleles suggested the known psoriasis risk allele <i>HLA-C*06:02</i> as a risk factor for tonsillitis (<i>P</i> = 4.8 × 10<sup>-4</sup>; OR, 2.3).
Four inflammatory diseases are strongly associated with Major Histocompatibility Complex class I (MHC-I) molecules: birdshot chorioretinopathy (HLA-A<sup>*</sup>29:02), ankylosing spondylitis (HLA-B<sup>*</sup>27), Behçet's disease (HLA-B<sup>*</sup>51), and psoriasis (HLA-C<sup>*</sup>06:02).
Expanding on the previously reported experience with this patient, we conclude that HLA-C*18:01 probably indicates a severe, recalcitrant, multidrug-resistant psoriasis phenotype for which proper therapy remains to be identified.
Case-control analysis revealed an association of IL12B rs3212227 and IL23R rs11209026 minor allele carrier status with reduced odds for psoriasis (OR = 0.66, 95%CI: 0.50-0.87, and OR = 0.41, 95%CI: 0.26-0.67, respectively), while HLA-C*06 allele carriers were more frequent in patients group (OR = 4.56, 95%CI: 3.41-6.10).
Furthermore, when combining the results of both the stepwise regression analysis and the HLA-C*06:02 conditioning analysis, different variants were found to be independently associated with each psoriasis subgroup.
PSORS1C2 is a gene located between coiled-coil alpha-helical rod protein 1 (CCHCR1) and corneodesmosin (CDSN) within the psoriasis susceptibility locus 1 (PSORS1).
Deletion of two members, LCE3B and LCE3C (LCE3B/C-del), is a widely-replicated psoriasis risk factor that interacts with the major psoriasis-psoriasis risk gene HLA-C*06.
Deletion of late cornified envelope (LCE) genes LCE3B and LCE3C (LCE3B/C-del) is a psoriasis risk factor linked to the major psoriasis risk gene HLA-C*06.Niehues et al. demonstrate that LCE3B/C-del leads to increased keratinocyte LCE3A expression.
The association between geographic tongue and psoriasis has been demonstrated in various studies, based on observation of its fundamental lesions, microscopic similarity between the two conditions and the presence of a common genetic marker, human leukocyte antigen (HLA) HLA-C*06.
After controlling for the age of psoriasis onset no association of PsA to HLA-C*06:02 (p=0.07) was observed; instead, the most significant association was to amino acid at position 97 of HLA-B (p=1.54×10<sup>-9</sup>) where the presence of asparagine or serine residue increased PsA risk.
We have investigated the association and possible functional role of non-synonymous SNPs at different exons of ERAP1 (rs26653: Arg127Pro, rs30187: rs30187" genes_norm="51752">Lys528Arg and rs27044: rs27044" genes_norm="51752">Gln730Glu) and their interactions with HLA-C∗06 in psoriasis.
To determine the structural basis of this selectivity, we determined crystal structures of HLA-C*06:02 in complex with two self-peptides (ARTELYRSL and ARFNDLRFV) and an analogue of a melanocyte autoantigen (ADAMTSL5, VRSRR-abu-LRL) implicated in psoriasis.