Feedback regulation of VISTA and Treg by TNF-α controls T cell responses in drug allergy.

Background: Severe cutaneous adverse reactions (SCARs) mediated by cytotoxic T lymphocytes are a series of life-threatening conditions with a mortality of 4%-20%. The clinical application of tumor necrosis factor-alpha (TNF-α) antagonist improves the outcome of some SCARs patients; however, this is complicated by the elusive and varied immunopathogenesis.

Aim: To investigate whether IgE antibody responses to HEMAs are associated with AD, its severity, and response to dupilumab.

Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients of Bullous Pemphigoid with or without Parkinson's Disease.

Background: High positivity rate of skin phosphorylated α-synuclein (P-SYN) was observed in Parkinson's disease (PD). Bullous pemphigoid (BP) is one of the most common autoimmune skin diseases associated with PD.

Objectives: Our aim was to investigate whether BP patients might be a targeted risk population for the screening of skin P-SYN.

Case report: Intralesional secukinumab injection for pediatric nail psoriasis: does it have to be a positive outcome?

Recent studies have shown that local injection of secukinumab can achieve positive therapeutic effects when applied in the treatment of nail psoriasis. At present, there have been no other studies on the use of biological agents in the treatment of pediatric nail psoriasis. Three children were included in the study to evaluate the efficacy and safety of periungual injection and long-term injection of secukinumab in the treatment of nail psoriasis in children.

Pathomechanism of Adverse Reactions to Biological Treatment of Inflammatory Skin Conditions.

Biological agents are widely used across medicine, including for immune-mediated skin conditions such as psoriasis and atopic dermatitis. When used to treat a relevant pathological process, they demonstrate impressive efficacy and credible safety, helping to achieve remission and improved function and quality of life. However, with their expanded use, awareness and understanding of adverse reactions to biologicals have also increased.

Single-cell transcriptomics analysis of bullous pemphigoid unveils immune-stromal crosstalk in type 2 inflammatory disease.

Bullous pemphigoid (BP) is a type 2 inflammation- and immunity-driven skin disease, yet a comprehensive understanding of the immune landscape, particularly immune-stromal crosstalk in BP, remains elusive. Herein, using single-cell RNA sequencing (scRNA-seq) and in vitro functional analyzes, we pinpoint Th2 cells, dendritic cells (DCs), and fibroblasts as crucial cell populations. The IL13-IL13RA1 ligand-receptor pair is identified as the most significant mediator of immune-stromal crosstalk in BP.

HLA-C*15:02 and epidermal growth factor receptor inhibitor-induced erosive pustular dermatosis of the scalp.

Epidermal growth factor receptor inhibitors (EGFRIs) are widely used to treat various types of malignancies. One of the common adverse reactions is cutaneous toxicity, mostly presenting as acneiform eruptions, paronychia and xerosis. Erosive pustular dermatosis of the scalp (EPDS) is a rare cutaneous adverse reaction that develops during treatment with EGFRIs.

Single-cell sequencing analysis reveals development and differentiation trajectory of Schwann cells manipulated by M. leprae.

Background: M. leprae preferentially infects Schwann cells (SCs) in the peripheral nerves leading to nerve damage and irreversible disability. Knowledge of how M.

TAP2 Drives HLA-B∗13:01‒Linked Dapsone Hypersensitivity Syndrome Tolerance and Reactivity.

Dapsone hypersensitivity syndrome (DHS) is restricted to HLA-B∗13:01. However, the positive predictive value for HLA-B∗13:01 is only 7.8%.

IL-23/IL-23R Promote Macrophage Pyroptosis and T Helper 1/T Helper 17 Cell Differentiation in Mycobacterial Infection.

Pathogen-induced epigenetic modifications can reshape anti-infection immune processes and control the magnitude of host responses. DNA methylation profiling has identified crucial aberrant methylation changes associated with diseases, thus providing biological insights into the roles of epigenetic factors in mycobacterial infection. In this study, we performed a genome-wide methylation analysis of skin biopsies from patients with leprosy and healthy controls.

Activation of Human CD8+ T Cells with Nitroso Dapsone-Modified HLA-B*13:01-Binding Peptides.

Previous studies have shown that cysteine-reactive drug metabolites bind covalently with protein to activate patient T cells. However, the nature of the antigenic determinants that interact with HLA and whether T cell stimulatory peptides contain the bound drug metabolite has not been defined. Because susceptibility to dapsone hypersensitivity is associated with the expression of HLA-B*13:01, we have designed and synthesized nitroso dapsone-modified, HLA-B*13:01 binding peptides and explored their immunogenicity using T cells from hypersensitive human patients.

Detection of Hepatic Drug Metabolite-Specific T-Cell Responses Using a Human Hepatocyte, Immune Cell Coculture System.

Drug-responsive T-cells are activated with the parent compound or metabolites, often via different pathways (pharmacological interaction and hapten). An obstacle to the investigation of drug hypersensitivity is the scarcity of reactive metabolites for functional studies and the absence of coculture systems to generate metabolites in situ. Thus, the aim of this study was to utilize dapsone metabolite-responsive T-cells from hypersensitive patients, alongside primary human hepatocytes to drive metabolite formation, and subsequent drug-specific T-cell responses.

Identification of the BTN3A3 Gene as a Molecule Implicated in Generalized Pustular Psoriasis in a Chinese Population.

The discovery of pathogenic variants provided biological insight into the role of host genetic factors in generalized pustular psoriasis (GPP). However, not all those affected by GPP carry variants in the reported genes. To comprehensively explore the molecular pathogenesis of GPP, whole-exome sequencing was performed, and two loci were identified with exome-wide significance through single variant association analysis: rs148755083 in the IL36RN gene (P = 1.