Psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors.

PD-1 (programmed Death-1) immune checkpoint inhibitors have provided significant benefits to tumor patients. However, a considerable proportion of the patients develop immune-related adverse events (irAEs), of which cutaneous irAEs (cirAEs, e.g., psoriasis) occur relatively early. This review provides an overview of the current progress in psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. It not only describes the relevant influencing factors but also theoretically analyzes the immunological mechanisms that lead to the onset or exacerbation of psoriasis. Finally, the authors present guidelines for the treatment of psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. The review is intended to assist dermatologists in the early recognition and effective individualized management of such cirAE, which is helpful to continue or adjust the tumor-targeted immunotherapy on the basis of ensuring the quality of life of tumor patients.

Psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors

Abstract PD-1 (programmed Death-1) immune checkpoint inhibitors have provided significant benefits to tumor patients. However, a considerable proportion of the patients develop immune-related adverse events (irAEs), of which cutaneous irAEs (cirAEs, e.g., psoriasis) occur relatively early. This review provides an overview of the current progress in psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. It not only describes the relevant influencing factors but also theoretically analyzes the immunological mechanisms that lead to the onset or exacerbation of psoriasis. Finally, the authors present guidelines for the treatment of psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. The review is intended to assist dermatologists in the early recognition and effective individualized management of such cirAE, which is helpful to continue or adjust the tumor-targeted immunotherapy on the basis of ensuring the quality of life of tumor patients.

Skin microbial dysbiosis is a characteristic of systemic drug-related intertriginous and flexural exanthema-like lesions induced by EGFR inhibitor.

Objectives: To investigate the characteristics of the skin microbiome in severe afatinib-induced skin toxicity. Methods: Body site-matched skin surface samples were collected from the lesions on seven flexural sites of one lung cancer (Patient 1) with serious systemic drug-related intertriginous and flexural exanthema (SDRIFE)-like toxicity induced by EGFR-TKI and three healthy age/sex matched controls for whole metagenomics sequencing analysis. Lung cancer Patient 1 and Patient 2 were prescribed minocycline and followed up. Results: In SDRIFE-like toxicities induced by afatinib, lesion microbiota richness (ACE and Chao1 index: p < 0.001) and diversity (Shannon's and Simpson's diversity indices: p < 0.01) were reduced. Similarly, the beta diversity analysis (R = 1, p = 0.002 for ANOSIM) showed that the apparent difference in the microbiota composition was statistically significant. The microbial taxa composition in the patient showed an increased abundance of pathogenic bacteria and a decreased abundance of commensal bacteria. LEfSe analysis identified strong bacterial pathogenicity in the patient, while healthy controls exhibited enrichment in several pathways that are beneficial for skin commensal bacteria and skin physiology, including key amino acid metabolism, energy/lipid/glycan biosynthesis/metabolism, and cofactors/vitamins biosynthesis. Ultimately, the patients experienced significant improvement with minocycline. Conclusion: Microbial dysbiosis is a characteristic of severe SDRIFE-like toxicity induced by afatinib.

Single-cell transcriptomic landscape of immunometabolism reveals intervention candidates of ascorbate and aldarate metabolism, fatty-acid degradation and PUFA metabolism of T-cell subsets in healthy controls, psoriasis and psoriatic arthritis.

Introduction: The modulation of immunometabolic pathways is emerging as a promising therapeutic target for immune-mediated diseases. However, the immunometabolic features of psoriatic disease and the potential targets for immunometabolic intervention in the different T-cell subsets involved in its pathogenesis remain unclear. Methods: In this study, we analyzed circulating blood single-cell data from healthy controls (HC), psoriasis (PSO), and psoriatic arthritis (PSA) patients, and revealed their metabolic features of T-cell subsets: CD4+ central memory T cells (TCMs), CD8+ effective memory T cells (TEMs), regulatory T cells (Tregs), mucosal-associated invariant T cells (MAITs ), and γδ T cells. Pearson test was performed to determine the linkages between differential metabolic and inflammatory pathways. Based on these results, we also analyzed the potential impacts of biological antibodies on differential metabolic pathways by comparing the immunometabolism differences between PSA patients without and with biological treatment. Results: Our results suggest that upregulation of ascorbate and aldarate metabolism, as well as fatty acid degradation, may enhance the immune suppression of Tregs. Enhanced metabolism of alpha-linolenic acid, linoleic acid, and arachidonic acid may inhibit the pro-inflammatory functions of CD4+ TCMs and CD8+ TEMs in PSO and PSA, and protect the immune suppression of Tregs in PSA. We propose that supporting ascorbic acid and fatty acid metabolic pathways may be an adjunctive reprogramming strategy with adalimumab and etanercept therapy. Discussion: These findings not only provide insights into immunometabolism characteristics of psoriatic disease, but also offer preliminary options for the auxiliary treatment of psoriasis.

Analysis of CD8+ TCRß Chain repertoire in peripheral blood of vitiligo via high-throughput sequencing.

Vitiligo is an autoimmune depigmentation dermatosis induced by melanocyte destruction, and CD8+ T cells play a pivotal role in melanocyte destruction. However, an accurate profile of the CD8+ T cell receptor (TCR) repertoire in vitiligo patients has not been reported, and the clonotype features of the involved CD8+ T cells remain largely unknown. This study aimed to assess the TCRß chain repertoire diversity and composition of blood in nine nonsegmental vitiligo patients via high-throughput sequencing. Vitiligo patients manifested a low TCRß repertoire diversity with highly expanded clones. Differential usage of TRBV, the TRBJ gene, and the TRBV/TRBJ combination were compared between patients with vitiligo and healthy controls. A set of TRBV/TRBJ combinations could differentiate patients with vitiligo from healthy controls (area under the curve = 0.9383, 95% CI: 0.8167-1.00). Our study revealed distinct TCRß repertoires of CD8+ T cells in patients with vitiligo and will help explore novel immune biomarkers and potential therapeutic targets for vitiligo.

Warfarin-induced Stevens-Johnson syndrome with severe liver injury.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a life-threatening mucocutaneous disease that is predominantly drug-induced. Warfarin is the most commonly used drug for long-term anti-coagulant therapy; however, warfarin-induced SJS/TEN is seldom reported. In this study, we presented the case of a 61-year-old man who developed SJS after receiving multiple-drug therapy following aortic valve replacement surgery. The patient was diagnosed with drug-induced liver injury (DILI) based on significantly abnormal liver function test results. Warfarin was identified as the culprit drug using the algorithm of drug causality for epidermal necrolysis (ALDEN) score, enzyme-linked immunospot (ELISPOT) assay, and Roussel Uclaf Causality Assessment Method (RUCAM). After warfarin discontinuation and corticosteroid therapy, the lesions and liver function test findings improved. Human leukocyte antigen typing was conducted to detect the risk allele. To our knowledge, this is the first reported case of warfarin-induced SJS/TEN with DILI. This case suggests that commonly used and safe pharmaceutical agents such as warfarin can potentially cause serious adverse events, including SJS/TEN and DILI. The application of ALDEN, the ELISPOT assay, and RUCAM could be useful in identifying culprit drugs.

MicroRNA-150 inhibitors enhance cell apoptosis of melanoma by targeting PDCD4.

Malignant melanoma is a tumor with a high mortality rate. Previous studies have demonstrated that the oncogenesis of melanoma is associated with microRNA (miR)-150. However, the role of miR-150 in melanoma and its regulatory mechanisms are still unclear. In the present study, melanoma cancer tissues and adjacent normal tissues were obtained from 20 melanoma patients. The expression level of miR-150 in melanoma tissue and cell lines was detected by reverse transcription-quantitative polymerase chain reaction. miR-150 inhibitors/negative control were transfected into melanoma A375 cells in order to investigate the effects of miR-150 on cell proliferation, apoptosis, cell cycle migration and invasion using a Cell Counting Kit-8, colony formation, Hoechst 33528, flow cytometry, and Transwell assays. The association between miR-150 and programmed cell death protein-4 (PDCD4) was detected by a dual luciferase reporter assay. The functional role of PDCD4 in miR-150-affected melanoma cells was confirmed by small interfering (si)RNA knockdown. Results demonstrated that miR-150 was significantly upregulated and mRNA and protein expressions of PDCD4 were decreased in melanoma cancer tissues as compared with adjacent normal tissues. The level of PDCD4 was inversely associated with the level of miR-150. Transfection of miR-150 inhibitors suppressed cell proliferation, migration, and invasion, while the apoptosis of cells was promoted and G2/M cell arrest was induced. MiR-150 inhibitors enhanced the expression of caspase-8 and p21. The PDCD4 was identified as a direct target gene of miR-150. The effects of miR-150 inhibitors on apoptosis and apoptosis-associated proteins, including caspase-8 and p21, of A375 cells, were reversed following transfection of siRNA-PDCD4. Therefore, miR-150 inhibitors enhance cell apoptosis via upregulation of PDCD4-mediated activation of caspase-8 and p21. These findings demonstrate the potential for a promising therapeutic strategy in the management of melanoma.