Bone marrow mastocytosis associated with primary cutaneous follicle center lymphoma: an unusual case report.

In a subset of patients with systemic mastocytosis (SM), an associated hematologic neoplasm (AHN) is identified. Most AHN are myeloid neoplasms, whereas lymphoid neoplasms are uncommon. We report on a 70-year-old female patient with bone marrow mastocytosis (BMM) associated with primary cutaneous follicle center lymphoma (PCFCL).

Epiplakin expression is lost in psoriatic skin lesions and is downregulated by IFN-γ in skin cultures.

Proteins of the plakin family are predominantly expressed in the epidermis and play a crucial role in cytoskeletal assembly by crosslinking intracellular structural components with cell-cell junctions and the plasma membrane. While most plakins are critical for maintaining epidermal integrity, the role of epiplakin (EPPK1) in inflammatory skin disorders has not been thoroughly investigated. We therefore used single-cell RNA sequencing (scRNAseq) analysis, immunofluorescence, and cytokine treatment of human skin explants to investigate EPPK1 regulation in psoriasis.

A Sex-Specific Anti-Inflammatory Role for p62 in Psoriasis-Like Disease.

Psoriasis is a chronic inflammatory skin disease involving a complex cross-talk between immune and epidermal cells. Psoriasis is difficult to treat and often complicated by systemic manifestations such as psoriatic arthritis. SQSTM1/p62 is a multifunctional adaptor protein controlling autophagy, cell differentiation, and inflammation that was found elevated in human psoriatic skin.

Single-cell RNA sequencing of chronic idiopathic erythroderma defines disease-specific markers.

Background: Chronic erythroderma is a potentially life-threatening condition that can be caused by various diseases, but approximately 30% of cases remain idiopathic, often with insufficient treatment options.

Objective: We sought to establish a molecular disease map of chronic idiopathic erythroderma (CIE).

Methods: We performed single-cell RNA sequencing combined with T-cell receptor sequencing of blood and skin from 5 patients with CIE and compared results with 8 cases of erythrodermic cutaneous T-cell lymphoma (eCTCL), 15 cases of moderate to severe atopic dermatitis, 10 cases of psoriasis, and 20 healthy control individuals.

JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia.

The hair follicle stem cell niche is an immune-privileged microenvironment, characterized by reduced antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrated the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) against scarring hair follicle destruction. Mechanistically, disruption of EGFR signaling generated a cell-intrinsic hypersensitivity within the JAK-STAT1 pathway, which, synergistically with interferon gamma expressing CD8 T-cell and NK-cell-mediated inflammation, compromised the stem cell niche.

Single-cell RNA sequencing comparison of CD4+, CD8+ and T-cell receptor γδ+ cutaneous T-cell lymphomas reveals subset-specific molecular phenotypes.

Background: Malignant clones of primary cutaneous T-cell lymphomas (CTCL) can show a CD4+, CD8+ or T-cell receptor (TCR)-γδ+ phenotype, but their individual impact on tumour biology and skin lesion formation remains ill defined.

Objectives: To perform a comprehensive molecular characterization of CD4+ vs. CD8+ and TCR-γδ+ CTCL lesions.

ReactomeGSA: new features to simplify public data reuse.

Motivation: ReactomeGSA is part of the Reactome knowledgebase and one of the leading multi-omics pathway analysis platforms. ReactomeGSA provides access to quantitative pathway analysis methods supporting different 'omics data types. Additionally, ReactomeGSA can process different datasets simultaneously, leading to a comparative pathway analysis that can also be performed across different species.

Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells.

Dupilumab, an IL4R-blocking antibody, has shown clinical efficacy for atopic dermatitis (AD) treatment. In addition to conjunctivitis/blepharitis, the de novo appearance of head/neck dermatitis is now recognized as a distinct side effect, occurring in up to 10% of patients. Histopathological features distinct from AD suggest a drug effect, but exact underlying mechanisms remain unknown.

Evaluation of mortality, prognostic parameters, and treatment efficacy in mycosis fungoides.

Background And Objectives: Mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, is characterized by a variable clinical course, presenting either as indolent disease or showing fatal progression due to extracutaneous involvement. Importantly, the lack of prognostic models and predominantly palliative therapy settings hamper patient care. Here, we aimed to define survival rates, disease prediction accuracy, and treatment impact in MF.

Cornification of keratinocytes is associated with differential changes in the catalytic activity and the immunoreactivity of transglutaminase-1.

Transglutaminase 1 (TGM1) plays an essential role in skin barrier formation by cross-linking proteins in differentiated keratinocytes. Here, we established a protocol for the antibody-dependent detection of TGM1 protein and the parallel detection of TGM activity. TGM1 immunoreactivity initially increased and co-localized with membrane-associated TGM activity during keratinocyte differentiation.

The Reactome Pathway Knowledgebase 2024.

The Reactome Knowledgebase (https://reactome.org), an Elixir and GCBR core biological data resource, provides manually curated molecular details of a broad range of normal and disease-related biological processes. Processes are annotated as an ordered network of molecular transformations in a single consistent data model.

No impact of disease duration on response to tildrakizumab treatment among patients with moderate-to-severe plaque psoriasis: Post hoc analyses from two phase 3 (reSURFACE 1 and reSURFACE 2) and one phase 4 (TRIBUTE) studies.

In the literature there is no consensus on the correlation between early systemic intervention and better treatment response in psoriasis. Here we present data on the impact of disease duration (<5 years, 5-<10 years, and ≥10 years) on response to tildrakizumab treatment among patients with moderate-to-severe plaque psoriasis from the reSURFACE 1 and reSURFACE 2 phase 3 trials and the TRIBUTE phase 4 study. Overall, there was no significant effect of disease duration on the Psoriasis Area and Severity Index ≤1, ≤3, and ≤5, or the Dermatology Life Quality Index 0-1 response rates.

Single-cell RNA sequencing defines disease-specific differences between chronic nodular prurigo and atopic dermatitis.

Background: Chronic nodular prurigo (CNPG) is an inflammatory skin disease that is maintained by a chronic itch-scratch cycle likely rooted in neuroimmunological dysregulation. This condition may be associated with atopy in some patients, and there are now promising therapeutic results from blocking type 2 cytokines such as IL-4, IL-13, and IL-31.

Objectives: This study aimed to improve the understanding of pathomechanisms underlying CNPG as well as molecular relationships between CNPG and atopic dermatitis (AD).

Using the Reactome Database.

Pathway databases provide descriptions of the roles of proteins, nucleic acids, lipids, carbohydrates, and other molecular entities within their biological cellular contexts. Pathway-centric views of these roles may allow for the discovery of unexpected functional relationships in data such as gene expression profiles and somatic mutation catalogues from tumor cells. For this reason, there is a high demand for high-quality pathway databases and their associated tools.

A Comprehensive Evaluation of Consensus Spectrum Generation Methods in Proteomics.

Spectrum clustering is a powerful strategy to minimize redundant mass spectra by grouping them based on similarity, with the aim of forming groups of mass spectra from the same repeatedly measured analytes. Each such group of near-identical spectra can be represented by its so-called consensus spectrum for downstream processing. Although several algorithms for spectrum clustering have been adequately benchmarked and tested, the influence of the consensus spectrum generation step is rarely evaluated.

scAnnotatR: framework to accurately classify cell types in single-cell RNA-sequencing data.

Background: Automatic cell type identification is essential to alleviate a key bottleneck in scRNA-seq data analysis. While most existing classification tools show good sensitivity and specificity, they often fail to adequately not-classify cells that are missing in the used reference. Additionally, many tools do not scale to the continuously increasing size of current scRNA-seq datasets.

The reactome pathway knowledgebase 2022.

The Reactome Knowledgebase (https://reactome.org), an Elixir core resource, provides manually curated molecular details across a broad range of physiological and pathological biological processes in humans, including both hereditary and acquired disease processes. The processes are annotated as an ordered network of molecular transformations in a single consistent data model.

Omalizumab-Induced Aspirin Tolerance in Nonsteroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease Patients Is Independent of Atopic Sensitization.

Background: Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) comprises the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to inhibitors of the cyclooxygenase-1 enzyme. The impact of omalizumab on prevention of aspirin-induced hypersensitivity in N-ERD patients with and without atopic sensitization has not been thoroughly addressed.

Objective: To investigate the effect of omalizumab treatment on aspirin tolerance in atopic and nonatopic N-ERD patients.

A proteomics sample metadata representation for multiomics integration and big data analysis.

The amount of public proteomics data is rapidly increasing but there is no standardized format to describe the sample metadata and their relationship with the dataset files in a way that fully supports their understanding or reanalysis. Here we propose to develop the transcriptomics data format MAGE-TAB into a standard representation for proteomics sample metadata. We implement MAGE-TAB-Proteomics in a crowdsourcing project to manually curate over 200 public datasets.

Single-cell analysis reveals innate lymphoid cell lineage infidelity in atopic dermatitis.

Background: Although ample knowledge exists about phenotype and function of cutaneous T lymphocytes, much less is known about the lymphocytic components of the skin's innate immune system.

Objective: To better understand the biologic role of cutaneous innate lymphoid cells (ILCs), we investigated their phenotypic and molecular features under physiologic (normal human skin [NHS]) and pathologic (lesional skin of patients with atopic dermatitis [AD]) conditions.

Methods: Skin punch biopsies and reduction sheets as well as blood specimens were obtained from either patients with AD or healthy individuals.

Loss of Lymphotoxin Alpha-Expressing Memory B Cells Correlates with Metastasis of Human Primary Melanoma.

Activated antigen-experienced B cells play an unexpected complex role in anti-tumor immunity in human melanoma patients. However, correlative studies between B cell infiltration and tumor progression are limited by the lack of distinction between functional B cell subtypes. In this study, we examined a series of 59 primary and metastatic human cutaneous melanoma specimens with B cell infiltration.

A Standardized Analysis of Tertiary Lymphoid Structures in Human Melanoma: Disease Progression- and Tumor Site-Associated Changes With Germinal Center Alteration.

There is increasing evidence that tertiary lymphoid structures (TLS) control not only local adaptive B cell responses at melanoma tumor sites but also the cellular composition and function of other immune cells. In human melanoma, however, a comprehensive analysis of TLS phenotypes, density and spatial distribution at different disease stages is lacking. Here we used 7-color multiplex immunostaining of whole tissue sections from 103 human melanoma samples to characterize TLS phenotypes along the expression of established TLS-defining molecular and cellular components.

Analysis of Label-Based Quantitative Proteomics Data Using IsoProt.

Isobaric labeling has become an essential method for quantitative mass spectrometry based experiments. This technique allows high-throughput proteomics while providing reasonable coverage of protein measurements across multiple samples. Here, the analysis of isobarically labeled mass spectrometry data with a special focus on quality control and potential pitfalls is discussed.