Inflammasome activation in the innate immune response plays a role in the pathogenesis of psoriasis largely due to the increased levels of pro-inflammatory cytokines. However, the precise role of inflammasomes in psoriasis (Ps) and psoriatic arthritis (PsA) is largely undefined. To establish the reliability of inflammasome signaling proteins as diagnostics and predictive biomarkers of clinical severity in this disease population, serum from healthy donors and patients with Ps/PsA were analyzed for the protein expression of caspase-1, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), interleukin (IL)-1b and IL-18 levels to determine cutoff points, positive and negative predictive values, and receiver operator characteristic (ROC) curves. Our data revealed that ASC and IL-18 proteins were significantly higher in the Ps group when compared to healthy controls. The area under the curve (AUC) for ASC was 0.9224 with a cutoff point of 321.8 pg/ml, while IL-18 had an AUC of 0.7818 and a cutoff point of 232.1 pg/ml. In addition, levels of IL-18 had a statistically significant linear correlation with that of ASC with an adjusted R squared of 0.2566, indicating that approximately 25% of IL-18 levels could be explained by ASC levels in serum. Our findings indicate that ASC and IL-18 play a significant role in the inflammatory response associated with the pathology of Ps. These inflammasome proteins appear to be key biomarkers in determining diagnoses in this patient population.

BackgroundInterleukin (IL)-1β is involved in the pathology of intervertebral disc degeneration. Under normal conditions, IL-1β is present in cells in an inactive form (pro-IL-1β). However, under pathological conditions, pro-IL-1β is turned into its active form (IL-1β) by the inflammasome, a multi-protein complex of the innate immune response that activates caspase-1. Under conditions of degeneration, the disc experiences an environment of increased acidification. However, the implications of acidification on the innate immune response remain poorly explored.MethodsHere we have studied how pH changes in human nucleus pulposus cells affect inflammasome activation by immunoblot analysis of protein lysates obtained from nucleus pulposus cells that were exposed to different pH levels in culture.ResultsIn this study, we have found that in nucleus pulposus cells, with increased acidification, there was a decrease in inflammasome activation consistent with lower levels of active IL-1β. However, this effect at a pH of 6.5, the lowest pH level tested, was abrogated when cells were treated with IL-1β.ConclusionsTaken together, these findings suggest that the inflammatory response through IL-1β experienced by the human disc is not initiated in nucleus pulposus cells when the stimulus is acidification.Electronic supplementary materialThe online version of this article (doi:10.1186/s12950-016-0137-0) contains supplementary material, which is available to authorized users.

Kyrle's disease (KD) is a cutaneous disease that develops in individuals with underlying systemic disease, particularly chronic renal failure and diabetes mellitus (DM), and is associated with a high burden of disease linked to itch. The intensely pruritic, hyperkeratotic papulonodular rash seen in KD dramatically impairs patients’ quality of life and increases their risk of mortality. Unfortunately, no guidelines or evidence‐based regimens have been specifically developed for KD, making the treatment of this disease particularly challenging for physicians. This article aims to provide the first comprehensive, up‐to‐date overview and analysis of treatment options employed for KD. A search of the PubMed/MEDLINE and Scopus databases was performed for articles regarding the treatment of KD, published in English between 1990 and 2019. Seventy‐three articles were identified, of which eighteen met the inclusion criteria. We discovered that a wide variety of treatment regimens for KD have been reported in the literature, including oral antibiotics, immunosuppressants, phototherapy, topical/systemic retinoids, topical keratolytics and various combination therapies, which include some of the aforementioned treatments, in conjunction with oral/topical/injectable steroids, emollients and/or antihistamines. The use of a combination regimen is the most commonly practiced therapeutic approach to KD. Topical corticosteroids and depot corticosteroid injections repeatedly appeared in many of the regimens encountered during our search. While no definitive recommendations can be made based on existing literature, this article provides physicians with a summative outline that can help guide management and be referenced when other treatment efforts fail. The increasing prevalence of renal disease, DM and other chronic diseases will inevitably lead to rising rates of KD in the upcoming years. While randomized controlled trials are greatly needed, novel antipruritic immunomodulatory drugs targeting specific interleukin receptors (IL‐4/13/31) and intracellular signalling (e.g. Janus kinase) pathways may have a potential role in the treatment of this disease.

Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products.