C.M. Sweeney

Hidradenitis suppurativa: the role of immune dysregulation

Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory disease of follicular occlusion characterized by boils, sinus tracts, fistulae, and scarring. It has a significant underestimated morbidity. Antimicrobial, immunosuppressive, anti‐androgenic, and surgical approaches have been used with varying results. Knowledge of the pathogenesis of HS is fragmented, and treatment choices have hitherto been empiric without an exact understanding of the scientific basis for their use. Tumor necrosis factor‐α inhibitors have shown promise in the treatment of HS in recent years, and the concept of HS as an immunological condition has come to the fore. The focus of this review is to discuss the immunological abnormalities underpinning HS as elucidated to date.

Glucagon-like peptide-1 analogue therapy for psoriasis patients with obesity and type 2 diabetes: a prospective cohort study.

Backgroundu2002 Diabetes and obesity are more prevalent amongst psoriasis patients as is disturbance of the innate immune system. GLP‐1 analogue therapy considerably improves weight and glycaemic control in people with type 2 diabetes and its receptor is present on innate immune cells.

Notch-1 mediates endothelial cell activation and invasion in psoriasis

Notch receptor–ligand interactions are critical for cell proliferation, differentiation and survival; however, the role of Notch signalling in psoriasis remains to be elucidated. Serum amyloid A (A‐SAA) is an acute‐phase protein with cytokine‐like properties, regulates cell survival pathways and is implicated in many inflammatory conditions. To examine the role of Notch‐1 signalling in the pathogenesis of psoriasis, Notch‐1, DLL‐4, Jagged‐1, Hrt‐1/Hrt‐2, A‐SAA, Factor VIII and vascular endothelial growth factor (VEGF) mRNA and/or protein expression in psoriasis skin biopsies, serum and dHMVEC were assessed by immunohistology, dual‐immunofluorescence, real‐time PCR, ELISA and Western blotting. A‐SAA‐induced angiogenesis and invasion in the presence of Notch‐1 siRNA was assessed by matrigel tube formation assays and Transwell invasion assay. Increased Notch‐1, its ligand DLL‐4 and Hrt‐1 expression were demonstrated in lesional skin compared with non‐lesional skin, with greatest expression observed in the dermal vasculature (P < 0.05). Dual‐immunofluorescent staining demonstrated co‐localization of Notch‐1 to endothelial cell marker Factor VIII. A significant increase in A‐SAA levels was demonstrated in psoriasis serum compared with healthy control serum (P < 0.05), and A‐SAA expression was higher in lesional skin compared with non‐lesional. In dHMVEC, A‐SAA significantly induced Jagged‐1, Hrt‐1 and VEGF mRNA expression (P < 0.05) and activated Notch‐1 IC indicative of transcriptional regulation. In contrast, A‐SAA significantly inhibited DLL‐4 mRNA expression (P < 0.05). Finally A‐SAA‐induced angiogenesis and invasion were inhibited by Notch‐1 siRNA (P < 0.05). Notch receptor–ligand interactions mediate vascular dysfunction in psoriasis and may represent a potential therapeutic target.

Human β-Defensin 3 and Its Mouse Ortholog Murine β-Defensin 14 Activate Langerhans Cells and Exacerbate Psoriasis-Like Skin Inflammation in Mice

Our data show that one-third of patients with PD have autoantibodies to Col XVII that also bind to THþ neurons. The lack of reactivity of PD autoantibodies with skin suggests the autoantibodies develop from neuronal Col XVII. The subset of patients with neurologic disease that develop BP likely result from epitope spreading to regions of Col XVII that are pathogenic in skin. A key question that remains is whether Col XVII autoantibodies have a detrimental effect on PD or are otherwise predictive of disease onset/outcomes. Finally, these data suggest loss of tolerance to neuronal Col XVII may contribute to the risk for pemphigoid.

Framingham risk assessment in hidradenitis suppurativa

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Vitamin D status in hidradenitis suppurativa.

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Natural killer cells from psoriasis vulgaris patients have reduced levels of cytotoxicity associated degranulation and cytokine production.

Psoriasis vulgaris is a chronic inflammatory disease of the skin with a strong genetic component and immune system involvement. Although some evidence suggests that Natural Killer (NK) cells may play a part in psoriasis, their role is relatively unstudied and results are controversial. In this current study, NK cells from psoriasis patients exhibited reduced degranulation and produced lower levels of the pro-inflammatory cytokines IFN-γ and TNF-α. Further investigation found that NK cells from psoriasis patients and healthy controls expressed similar levels of activation markers, NK cell receptors and apoptosis-inducing molecules. In addition, comparable levels of several cytokines important in NK cell biology were found in the serum of psoriasis patients and healthy controls. Genotyping analysis revealed that HLA-C2, which provides a ligand for killer-cell immunoglobulin-like receptors (KIR) expressed by NK cells, was strongly associated with psoriasis susceptibility. However, no link between the KIR genes themselves and disease was found.

The pathogenic role of dendritic cells in non-infectious anterior uveitis

Background Anterior uveitis (AU) is characterised by infiltration of immune cells into the anterior chamber of the eye. Dendritic cells (DC) are professional antigen presenting cells that initiate and promote inflammation. This study aims to characterise DC in AU and to examine the effects of aqueous humor (AqH) on DC maturation and function. Methods The frequency and phenotype of AU and healthy control (HC) circulating DC was examined. AU and HC AqH was immunostained and assessed by flow cytometry. The effect of AU and HC AqH on DC activation and maturation was examined and subsequent effects on CD4+ T cell proliferation assessed. Results AU peripheral blood demonstrated decreased circulating myeloid and plasmacytoid DC. Within AU AqH, three populations of CD45+ cells were significantly enriched compared to HC; DCs (CD11c+ HLA‐DR+), neutrophils (CD15+ CD11c+) and T cells (CD4+ and CD8+). A significant increase in IFN&ggr;, IL8 and IL6 was observed in the AU AqH, which was also significantly higher than that of paired serum. AU AqH induced expression of CD40 and CD80 on DC, which resulted in increased T cell proliferation and the production of GM‐CSF, IFN&ggr; and TNF&agr;. Conclusion DC are enriched at the site of inflammation in AU. Our data demonstrate an increase in inflammatory mediators in the AU inflamed microenvironment. AU AqH can activate DC, leading to subsequent proliferation and activation of effector T cells. Thus, the AU microenvironment contributes to immune cell responses and intraocular inflammation. HighlightsDC are initiations of inflammation being involved in the unique immune deviation properties of the eye.This study analysed DC in circulation and locally in AU patients and examined the effects of AqH on a DC model.AU patients have decreased circulating DC. APCs, neutrophils and T cells are present in the inflamed anterior chamber during AU.AU AqH can activate a DC model with subsequent activation of T cells through the effect of released soluble mediators.This study supports a role of DC in the pathogenesis of AU. &NA; The anterior chamber in anterior uveitis (AU) patients contains inflammatory type dendritic cells (DC). AU aqueous humor activates DC, which subsequently activate effector T cells suggesting a role for DC in the pathogenesis of AU.

Adipokines are dysregulated in patients with hidradenitis suppurativa

Hidradenitis suppurativa (HS), is characterized by the appearance of painful subcutaneous nodules and dermal abscesses in the axillae, perineum and inframammary folds. The development of HS has been linked to factors such as cigarette smoking and obesity1. Patients with HS are more likely to have metabolic syndrome than control populations and develop early cardiovascular diseases2. Adipokines are signalling molecules secreted by adipose tissue and peripheral blood mononuclear cells. The expression of adipokines is dysregulated in obesity and cardiovascular diseases3. n nThis article is protected by copyright. All rights reserved.