The causal effect of interleukin-17 on the risk of psoriatic arthritis: a Mendelian randomization study.

OBJECTIVE: To determine causal associations between genetically predicted TNF-α, IL-12p70 and IL-17 levels and risk of PsA. METHODS: The publicly available summary-level findings from genome-wide association studies (GWAS) was used to identify loci influencing normal physiological concentrations of TNF-α, IL-12p70 and IL-17 (n = 8293) among healthy individuals as exposure and a GWAS for PsA from the UK Biobank (PsA = 900, control = 462 033) as the outcome. A two-sample Mendelian randomization (MR) analysis was performed using the inverse-variance weighted (IVW), weighted median and MR-Egger regression methods. Sensitivity analysis and MR-Egger regression analysis were performed to evaluate the heterogeneity and pleiotropic effects of each variant. RESULTS: Single-nucleotide polymorphisms (SNPs) at genome-wide significance from GWASs on TNF-α, IL-12p70 and IL-17 were identified as the instrumental variables. The IVW method indicated a causal association between increased IL-17 level and risk of PsA (ß = -0.00186 per allele, s.e. = 0.00043, P = 0.002). Results were consistent in the weighted median method (ß = -0.00145 per allele, s.e. = 0.00059, P = 0.014) although the MR-Egger method suggested a non-significant association (ß = -0.00133 per allele, s.e. = 0.00087; P = 0.087). Single SNP MR results revealed that the C allele of rs117556572 was robustly associated with risk of PsA (ß = 0.00210, s.e. = 0.00069, P = 0.002). However, no evidence for a causal effect was observed between TNF-α, IL-12p70, decreased IL-17 levels and risk of PsA. CONCLUSION: Our findings provide preliminary evidence that genetic variants predisposing to higher physiological IL-17 level are associated with decreased risk of PsA.

Progressive structural bone changes and their relationship with treatment in patients with psoriatic arthritis: a longitudinal HR-pQCT study.

BACKGROUND: Although the short-term effects of tumor necrosis factor alpha (TNF-α) and interleukin-17A (IL-17A) inhibition on the structural changes in psoriatic arthritis (PsA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) have been reported, no studies have investigated the long-term structural changes in PsA patients receiving routine care. We reported longitudinal changes of erosions and enthesiophytes using HR-pQCT and their relationship with treatments in PsA patients over a 5-year period. METHODS: HR-pQCT examination at the second and third metacarpal heads (MCH2 and MCH3) was performed in 60 PsA patients at baseline and after 5 years. The size of each individual lesion was quantified. Erosion and enthesiophyte progression were defined as change exceeding the smallest detectable change (SDC). RESULTS: A total of 108 bone erosions and 99 enthesiophytes were detected at baseline. Three new bone erosions but no new enthesiophytes were evident at 5 years. A significant increase in mean (±SD) erosion (0.58 ± 1.50 mm3, P < 0.001) and enthesiophyte (0.47 ± 0.76 mm3, P < 0.001) volume was observed. Erosion and enthesiophyte progression were found in 37/111 (33.3%) and 50/99 (50.5%) lesions, respectively. During this 5-year period, 26 (43%) out of the 60 patients achieved sustained Disease Activity index for PSoriatic Arthritis (DAPSA) low disease activity (LDA) (SDL group, defined as achieving DAPSA-LDA at both baseline and 5 years). Fourteen (23%) out of 60 patients received a TNF inhibitor throughout the 5-year period (TNFi group). Fewer erosions progressed (12/51 [23.5%] vs 25/60 [41.7%], P = 0.047) and the increased in enthesiophyte volume was significantly less (0.28 ± 0.67 vs 0.61 ± 0.80 mm3, P = 0.048) in the SDL group than in the non-SDL group. However, no significant difference between the TNFi and non-TNFi groups was detected in terms of the change in volume or progression of bone erosion and enthesiophyte. CONCLUSION: Damage accrual in terms of bone erosion and enthesiophyte was observed in PsA patients over a period of 5 years despite receiving routine clinical care. Nonetheless, sustained control of disease activity may be able to prevent these bony damages.