Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.
The recent observations described and discussed in this review raise the clinically significant possibility of redefining the immunological role of IL-17 in PsA and provide a basis for defining future studies to elucidate the molecular and cellular functions of Act1.
In the last years TRAF3IP2 gene variants had been described as associated with susceptibility to several diseases such as psoriasis and psoriatic arthritis.
TRAF3IP2 gene, associated with susceptibility to psoriatic arthritis and psoriasis, encodes for Act1, a negative regulator of adaptive immunity and a positive signaling adaptor in IL-17-mediated immune responses.
A stratified analysis of our datasets including only PsA cases (1,922 cases compared to 8,037 controls, P = 4.57 × 10⁻¹² for rs33980500) suggested that TRAF3IP2 represents a shared susceptibility for PsV and PsA.
Only three modestly sized genome-wide association studies of PsA have been undertaken to date, but they have identified the HLA-C region, IL12B, TRAF3IP2, and FBXL19 genes as being associated with PsA susceptibility.
Etanercept is a soluble tumor necrosis factor (TNF) receptor originally approved for treatment of moderate-to-severe rheumatoid arthritis, juvenile rheumatoid arthritis, and psoriatic arthritis.
Our results confirm the association between Cw*06 allele and psoriatic arthritis in the northern Poland population and suggest that the HLA-Cw*06 may determine not only the disease susceptibility, but also the age of onset of psoriatic arthritis.
Moreover, the genotype of patients in the PsA cohort was shown to be heterogeneous with significant elevations in the frequency of haplotypes containing HLA-B*08, HLA-C*06:02, HLA-B*27, HLA-B*38 and HLA-B*39.
To examine whether initiation of interleukin (IL)-17, IL-12/23 or tumour necrosis factor (TNF) inhibitor is associated with an increased risk of serious infection among real-world psoriasis (PsO) or psoriatic arthritis (PsA) patients.
In the last decade anti-tumor necrosis factor agents have shown to be effective for the treatment of both RA and PsA and some studies suggest that the interaction between TNFα and complement system may contribute to the pathogenesis of these diseases.
We aimed to characterize the PsA genotype by gene expression profile and to research the effect in gene modulation of methotrexate (MTX) and TNF-inhibitors (TNF-I) in PsA-treated patients.
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.
Anti-tumor necrosis factor-alpha (TNF-α) immunotherapy has revolutionized the treatment of inflammatory diseases, such as psoriasis and psoriatic arthritis.
HLA-C*06:02-negative patients were significantly more likely to respond to adalimumab than ustekinumab at all time points (most strongly at 6 months: odds ratio [OR], 2.95; P = 5.85 × 10<sup>-7</sup>), and the difference was greater in HLA-C*06:02-negative patients with psoriatic arthritis (OR, 5.98; P = 6.89 × 10<sup>-5</sup>).
Currently, along with traditional disease modifying anti-rheumatic drugs (DMARDs), TNF-α, IL-12/23 and IL-17 are available for treatment of such diseases as ankylosing spondylitis (AS) and psoriatic arthritis (PsA).
To analyse the association between the three common NOD2 variants (R702W, G908R and L1007fs) and clinical phenotypes of PsA, particularly with surrogate markers of severe joint destruction.