There is now growing evidence that psoriasis, like other inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus, is a systemic disorder that is associated with enhanced atherosclerosis and risk of coronary artery disease. Here we summarize the available epidemiological evidence for this association and analyse pathogenic features that are common to psoriasis and atherosclerosis. Further prospective studies are urgently needed to extend knowledge of the risk of cardiovascular morbidity and mortality in patients with psoriasis and to confirm the degree to which treatment of psoriasis reduces this risk. Nevertheless, existing data are sufficient to indicate that severe psoriasis should be more widely recognized as a potential risk factor for cardiovascular disease and should be considered with the established factors when formulating strategies for the management of cardiovascular risk.
Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07: 02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1 , encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07: 02.
The concept of using Mycobacterium for cancer treatment goes back to the 19th Century. Today, bacillus Calmette-Guerin (BCG) vaccine is a well-established treatment for human bladder cancer that is arguably superior to intravesical chemotherapy for superficial disease and is commonly used as the first-line adjuvant treatment. Much has been learnt about the effects of BCG on bladder cancer and the immune system, but deeper understanding is required in order to improve its efficacy further, to be able to reliably predict responders and ultimately to adapt this most successful form of cancer immunotherapy for the treatment of other malignancies. This article summarizes the current understanding of BCG cancer immunotherapy mechanisms and discusses possible future developments.
SUMMARY Intravesical immunotherapy for carcinoma in situ of the bladder is arguably the most effective form of tumour immunotherapy described to date. Following repeated instillations of BCG organisms into the bladder, large quantities of cytokines are detected in patients’ urine. This study concerns the production of IL‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, tumour necrosis factor‐alpha (TNF‐α), interferon‐gamma (IFN‐γ) and soluble ICAM‐1 (sICAM‐1) throughout the six weekly instillations which comprise a therapeutic course. Sequential instillations of BCG induced secretion of IL‐1β, IL‐2, IL‐6, IL‐8, IL‐10, TNF‐α, IFN‐γ and sICAM‐1 into urine. The responses were heterogeneous between patients and cytokines, but some general trends were evident. Although cytokine levels were initially low, their concentration increased with repeated instillation of BCG. Certain cytokines (e.g. IL‐6, IL‐8 and IL‐10) could be detected after the first instillation, whilst others (e.g. IL‐2 and IFN‐γ) were not detected until after the third or fourth instillation. Interestingly, IL‐4 was not detected, perhaps suggesting a differential effect on Th2‐like responses. Some patients produced particularly elevated or non‐detectable levels of cytokines, and a positive correlation was found between the production of various cytokines. The production of a particular cytokine did not correspond with lack of production of another species. Whether monitoring the production of cytokines following therapy may be of prognostic value will be determined in a larger series of patients. However, as these potent immunomodulators are thought t o be important for the 75% complete clinical response observed with BCG therapy, there remains the possibility that detection of the products of an activated immune system may correlate with eventual clinical outcome. This study is a necessary forerunner to full prognostic evaluation of such immunological data.
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