Porokeratosis (PK) is a heterogeneous group of keratinization disorders. No causal genes exceptMVKhave been identified, even though the disease was linked to several genomic loci. Here, we performed massively parallel sequencing and exonic CNV screening of 12 isoprenoid genes in 134 index PK patients (61 familial and 73 sporadic) and identified causal mutations in three novel genes (PMVK,MVD, andFDPS) in addition toMVKin the mevalonate pathway. Allelic expression imbalance (AEI) assays were performed in 13 lesional tissues. At least one mutation in one of the four genes in the mevalonate pathway was found in 60 (98%) familial and 53 (73%) sporadic patients, which suggests that isoprenoid biosynthesis via the mevalonate pathway may play a role in the pathogenesis of PK. Significantly reduced expression of the wild allele was common in lesional tissues due to gene conversion or some other unknown mechanism. A G-to-A RNA editing was observed in one lesional tissue without AEI. In addition, we observed correlations between the mutations in the four mevalonate pathway genes and clinical manifestations in the PK patients, which might support a new and simplified classification of PK under the guidance of genetic testing.

Previous studies have reported a higher incidence of depression and anxiety in psoriasis patients compared to the general population, which has important implications for assessment and treatment. In this study, we determined the frequency of depression and anxiety in Chinese patients with psoriasis and its relationship with disease severity and other demographic variables. The study included 208 Chinese patients with psoriasis vulgaris. The Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7) were used to screen for depression and anxiety. The Psoriasis Area and Severity Index (PASI) was used to assess the severity of psoriasis. Of the 208 patients included in the study, 29 patients (13.9%) were positive for moderate-to-severe depression (PHQ-9 ≥ 10) and 22 patients (10.6%) were positive for anxiety (GAD-7 ≥ 10) symptoms. Both positive stress reactors who perceived stress as an exacerbating factor of psoriasis and moderate-to-severe psoriasis were found to be positive predictors for the presence of moderate-to-severe depression or anxiety symptoms while longer duration and late onset age played a protective role. In the sample of Chinese patients with psoriasis there was a clinically significant prevalence of depression and anxiety. Our study suggests that Chinese psoriasis patients should be screened for psychiatric comorbidities.

Vγ9Vδ2 T cells play an important role in the development and progression of psoriasis vulgaris (PV), but how they promote skin inflammation and the molecular mechanisms underlying Vγ9Vδ2 T cell dysfunction are poorly understood. Here, we show that circulating Vγ9Vδ2 T cells are decreased and exhibit enhanced proliferation and increased production of IFN-γ and TNF-α in PV patients. Monocytes from PV patients express higher levels of the phosphoantigen sensor butyrophilin 3A1 (BTN3A1) than monocytes from healthy controls. Blockade of BTN3A1 suppresses Vγ9Vδ2 T cell activation and abolishes the difference in Vγ9Vδ2 T cell activation between PV patients and healthy controls. The CD14 ⁺ cells in PV skin lesions highly express BTN3A1 and juxtapose to Vδ2 T cells. In addition, IFN-γ induces the up-regulation of BTN3A1 on monocytes. Collectively, our results demonstrate a crucial role of BTN3A1 on monocytes in regulating Vγ9Vδ2 T cell activation and highlight BTN3A1 as a potential therapeutic target for psoriasis.

Background: Methotrexate (MTX) has a protective effect against cardiovascular diseases (CVD), but the mechanism is unclear.Objective: To investigate the effect of MTX on lipid profiles and the difference between psoriasis without arthritis (PsO) and psoriatic arthritis (PsA).Methods: In this prospective study, we recruited 288 psoriatic patients (136 PsA and 152 PsO) who completed 12 weeks of MTX treatment. Total cholesterol (TC), triglycerides (TG), lipoprotein A [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and ApoB were measured.Results: Compared with sex- and age-matched healthy controls, psoriatic patients had significantly (p< 0.0001) higher levels of proatherogenic lipids and lower levels of anti-atherogenic lipids. PsA patients had a higher ApoB/ApoA1 ratio than PsO patients (p< 0.05). Stepwise regression analysis found a positive correlation between the inflammatory marker hCRP and the Psoriasis Area Severity Index (PASI), ApoB/ApoA1 ratio, BMI, and smoking. ApoB was positively associated with concomitant arthritis, diabetes, and hypertension. MTX decreased the levels of pro-atherogenic and anti-atherogenic lipids. However, a significant reduction of the ApoB/ApoA1 ratio by MTX was only observed in male patients.Conclusion: PsA patients had a significantly higher percentage of concomitant disease than PsO. The decrease of MTX on CVD might be related with sex.Trial registration: ChiCTR2000036192