JAK2 and PTPRC mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus.

In this study, we aimed to explore the expression levels of JAK2 and PTPRC in peripheral blood mononuclear cells (PBMCs) from SLE patients and controls, detect the effects of SLE activity on genes mRNA expression, and find the association between genes mRNA expression and clinical manifestations of patients. We performed quantitative real-time PCR (qRT-PCR) to test differences in the expression levels of JAK2 and PTPRC in PBMCs extracted from 135 patients with SLE and 130 healthy controls. Furthermore, we detected the regulatory effect of SNPs on gene expression by expression quantitative trait loci (eQTL). We also tested whether the genes mRNA expression was affected with the SLE activity and analyzed the relationship between genes mRNA expression and clinical manifestations of patients. The mRNA expression levels of JAK2 in SLE patients were significantly higher than those in healthy controls (P = 0.005), and PTPRC mRNA expression levels were significantly decreased (P < 0.001). However, no other statistical significance was detected. We found that the elevated JAK2 mRNA expression and the decreased PTPRC mRNA expression may play suggestive roles in the pathogenesis of SLE.Key Points• The JAK2 mRNA expression levels in SLE patients were significantly higher than those in healthy controls.• The PTPRC mRNA expression levels in SLE were decreased.• JAK2 and PTPRC mRNA expression may play suggestive roles in the pathogenesis of SLE.

A KRT16 mutation in the first Chinese pedigree with Pachyonychia congenita and review of the literatures.

BACKGROUND: Pachyonychia congenita (PC), a rare autosomal dominant disorder, is featured by significant hypertrophic nail, palmoplantar keratoderma, and plantar pain. It is caused by the mutation of KRT6A, KRT6B, KRT6C, KRT16, or KRT17. AIMS: To identify the gene mutation caused the PC in a Chinese family. PATIENTS/METHODS: Genomic DNA was extracted from peripheral blood samples of five patients and six healthy individuals. Genomic DNA of three patients was sequenced by whole-exome sequencing (WES). Then, exons 6 of KRT16 of all samples were amplified by polymerase chain reaction (PCR), and PCR products were sequenced to identify potential mutations. RESULTS: We identified the proline substitution mutation p.Leu421Pro (c.1262T>C) in the 2B domain of K16 that is associated with PC in a Chinese family. The same mutation was not found in the six healthy individuals of the family. CONCLUSIONS: The mutation found in this study is the first report in China. So far, 25 mutations in KRT16 have been reportedly associated with PC. Twenty-one mutations are located on exon 1, and four mutations on exon 6.

Safety and Efficacy of Methotrexate for Chinese Adults With Psoriasis With and Without Psoriatic Arthritis.

Importance: It is necessary to determine whether psoriasis responds to methotrexate in the same manner in patients with and without psoriatic arthritis. Objective: To evaluate the effectiveness and safety of methotrexate in treating patients with psoriasis with and without psoriatic arthritis. Design, Setting, and Participants: In this prospective, single-arm, interventional study, a total of 235 patients with psoriasis, 107 without psoriatic arthritis and 128 with psoriatic arthritis who were receiving methotrexate therapy from April 1, 2015, to December 31, 2017, were recruited from the outpatient department of a hospital at a large Chinese university. There were no significant demographic or clinical differences between the subgroups with the exception of diabetes. Interventions: A 12-week course of low-dosage oral methotrexate (7.5-15 mg weekly). Main Outcomes and Measures: Changes in disease severity, adverse events, blood cell counts, and liver and renal function. Results: A total of 235 patients with psoriasis (166 male [66.0%]; mean [SD] age, 49.6 [15.1] years) received methotrexate treatment for 12 weeks. The 90% reduction from baseline Psoriasis Area Severity Index response was significantly lower in patients with psoriatic arthritis than in patients without psoriatic arthritis at week 8 (4 0f 128 [3.1%] vs 12 of 107 [11.2%]; P = .02) and week 12 (19 of 128 [14.8%] vs 27 of 107 [25.2%]; P = .049). Furthermore, the incidence of adverse events, including dizziness (12 of 128 [9.4%] vs 1 of 107 [0.9%]; P = .007), gastrointestinal symptoms (32 of 128 [25.0%] vs 13 of 107 [12.1%]; P = .01), and hepatoxicity (34 of 128 [26.6%] vs 16 of 107 [15.0%]; P = .04), was significantly higher in patients with psoriatic arthritis than in patients without psoriatic arthritis. Methotrexate-induced elevation of alanine aminotransferase levels was associated with body mass index (mean [SD] body mass index, 26 [4] in patients with [P = .04] vs 26 [4] in those without [P = .005] psoriatic arthritis) and smoking (17 of 34 [50.0%] in patients with [P = .02] vs 9 of 16 [56.3%] in those without [P = .04] psoriatic arthritis). Conclusions and Relevance: In this study, methotrexate was well tolerated and effective in treating psoriasis. It was more effective, with fewer adverse effects, in patients with psoriasis who did not have psoriatic arthritis than in patients who presented with both psoriasis and psoriatic arthritis. Therefore, methotrexate can be recommended as first-line treatment for psoriasis without arthritis.