Background: Select patients are diagnosed with both psoriasis (PSO) and hidradenitis suppurativa (HS), leading to a unique disease pattern. Genetic risk factors remain unidentified.
Methods: The study harnessed an international collection of patients with PSO and HS (PSO-SH).
Psoriasis is an immune-mediated inflammatory skin disease typically characterized by erythematous and scaly plaques. It affects 3% of the Newfoundland population while only affecting 1.7% of the general Canadian population.
View Article and Find Full Text PDFExpert Opin Biol Ther
December 2022
The IL-17A inhibitor secukinumab is efficacious for the treatment of psoriasis. To better understand its mechanism of action, we investigated its impact on psoriatic lesions from 15 patients with moderate-to-severe plaque psoriasis undergoing secukinumab treatment. We characterized the longitudinal transcriptomic changes of whole lesional skin tissue as well as cutaneous CD4 and CD8 T effector cells and CD4 T regulatory cells across 12 weeks of treatment.
View Article and Find Full Text PDFJ Psoriasis Psoriatic Arthritis
October 2021
Background: Despite numerous genome-wide association studies conducted in psoriasis and psoriatic arthritis, only a small fraction of the identified genes has been therapeutically targeted.
Objective: We sought to identify and analyze potential therapeutic targets for psoriasis and psoriatic arthritis (PsA) using the priority index (Pi), a genetics-dependent drug target prioritization approach.
Methods: Significant genetic variants from GWAS for psoriasis, PsA, and combined psoriatic disease were annotated and run through the Pi pipeline.
Ankylosing spondylitis (AS) is an immune-mediated inflammatory disorder that primarily affects the axial skeleton, especially the sacroiliac joints and spine. This results in chronic back pain and, in extreme cases, ankylosis of the spine. Despite its debilitating effects, the pathogenesis of AS remains to be further elucidated.
View Article and Find Full Text PDFEarly diagnosis of psoriatic arthritis (PSA) is important for successful therapeutic intervention but currently remains challenging due, in part, to the scarcity of non-invasive biomarkers. In this study, we performed single cell profiling of transcriptome and cell surface protein expression to compare the peripheral blood immunocyte populations of individuals with PSA, individuals with cutaneous psoriasis (PSO) alone, and healthy individuals. We identified genes and proteins differentially expressed between PSA, PSO, and healthy subjects across 30 immune cell types and observed that some cell types, as well as specific phenotypic subsets of cells, differed in abundance between these cohorts.
View Article and Find Full Text PDFRegulatory T cells (Tregs) reside in nonlymphoid tissues where they carry out unique functions. The molecular mechanisms responsible for Treg accumulation and maintenance in these tissues are relatively unknown. Using an unbiased discovery approach, we identified (layilin), a C-type lectin-like receptor, to be preferentially and highly expressed on a subset of activated Tregs in healthy and diseased human skin.
View Article and Find Full Text PDFBackground: Psoriasis is an inflammatory, IL-17-driven skin disease in which autoantigen-induced CD8 T cells have been identified as pathogenic drivers.
Objective: Our study focused on comprehensively characterizing the phenotypic variation of CD8 T cells in psoriatic lesions.
Methods: We used single-cell RNA sequencing to compare CD8 T-cell transcriptomic heterogeneity between psoriatic and healthy skin.
Intestinal microbiota are considered a sensor for molecular pathways, which orchestrate energy balance, immune responses, and cell regeneration. We previously reported that microbiota restriction promoted higher levels of systemic radiation-induced genotoxicity, proliferative lymphocyte activation, and apoptotic polarization of metabolic pathways. Restricted intestinal microbiota (RM) that harbors increased abundance of Lactobacillus johnsonii (LBJ) has been investigated for bacterial communities that correlated radiation-induced genotoxicity.
View Article and Find Full Text PDFProbiotics are considered to have multiple beneficial effects on the human gastrointestinal tract, including immunomodulation, pathogen inhibition, and improved host nutrient metabolism. However, extensive characterization of these properties is needed to define suitable clinical applications for probiotic candidates. 456 (LBJ 456) was previously demonstrated to have anti-inflammatory and anti-genotoxic effects in a mouse model.
View Article and Find Full Text PDFBackground: Psoriasis impacts 1-3% of the world's population and is characterized by hyper-proliferation of keratinocytes and increased inflammation. At the molecular level, psoriasis is commonly driven by a Th17 response, which serves as a major therapeutic target. Microbiome perturbations have been associated with several immune-mediated diseases such as atopic dermatitis, asthma, and multiple sclerosis.
View Article and Find Full Text PDFBackground: Propionibacteria are important members of the human skin microbiota, but are also opportunistic pathogens associated with periprosthetic joint infection (PJI). While the role of Propionibacterium acnes in PJI has been widely described, insight into the capacity of Propionibacterium avidum to cause PJI is limited.
Methods: An unusual cluster of 4 hip PJIs caused by P.
Recently, it has been proposed that strains of Propionibacterium acnes from the type III genetic division should be classified as P. acnessubsp. elongatum subsp.
View Article and Find Full Text PDFProgressive macular hypomelanosis (PMH) is a common skin disorder that causes hypopigmentation in a variety of skin types. Although the underlying aetiology of this condition is unclear, there is circumstantial evidence that links the skin bacterium Propionibacterium acnes to the condition. We now describe the first detailed population genetic analysis of P.
View Article and Find Full Text PDFThe viral population, including bacteriophages, is an important component of the human microbiota, yet is poorly understood. We aim to determine whether bacteriophages modulate the composition of the bacterial populations, thus potentially playing a role in health or disease. We investigated the diversity and host interactions of the bacteriophages of Propionibacterium acnes, a major human skin commensal implicated in acne pathogenesis.
View Article and Find Full Text PDFPropionibacterium acnes is a major skin commensal and is associated with acne vulgaris, the most common skin disease. Here we report the draft genome sequences of two P. acnes strains, the type strain ATCC6919 and an antibiotic-resistant strain, HL411PA1.
View Article and Find Full Text PDFAtaxia-telangiectasia is a genetic disorder associated with high incidence of B-cell lymphoma. Using an ataxia-telangiectasia mouse model, we compared lymphoma incidence in several isogenic mouse colonies harboring different bacterial communities, finding that intestinal microbiota are a major contributor to disease penetrance and latency, lifespan, molecular oxidative stress, and systemic leukocyte genotoxicity. High-throughput sequence analysis of rRNA genes identified mucosa-associated bacterial phylotypes that were colony-specific.
View Article and Find Full Text PDFUnlabelled: Propionibacterium acnes constitutes a major part of the skin microbiome and contributes to human health. However, it has also been implicated as a pathogenic factor in several diseases, including acne, one of the most common skin diseases. Its pathogenic role, however, remains elusive.
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