The pathogenic hallmark of systemic lupus erythematosus (SLE or lupus) is the autoimmune response against self nuclear antigens, including dsDNA. The increased expression of the pro-inflammatory cytokine IL-1β has been found in the cutaneous lesion and peripheral blood mononuclear cells from lupus patients, suggesting a potential involvement of this cytokine in the pathogenesis of lupus. IL-1β is produced primarily by innate immune cells like monocytes and can promote Th17 cell response, which is increased in lupus. IL-1β production requires cleaving pro-IL-β into IL-1β by the caspase-1-associated multiprotein complex called inflammasomes. Here we show that self dsDNA induces IL-1β production from human monocytes dependently of serum or purified IgG containing anti-dsDNA antibodies by activating the NLRP3 inflammasome. Reactive oxygen species (ROS) and K+ efflux were involved in this activation. Knocking down the NLRP3 or inhibiting caspase-1, ROS and K+ efflux decreased IL-1β production. Supernatants from monocytes treated with a combination of self dsDNA and anti-dsDNA antibody-positive serum promoted IL-17 production from CD4+ T cells in an IL-1β dependent manner. These findings provide new insights in lupus pathogenesis by demonstrating that self dsDNA together with its autoantibodies induces IL-1β production from human monocytes by activating the NLRP3 inflammasome through inducing ROS synthesis and K+ efflux, leading to the increased Th17 cell response.
The U1 snRNP immune complex is a specific stimulus of MIF production in human monocytes, with MIF having an upstream role in defining the inflammatory characteristics of activated monocytes by regulating NLRP3 inflammasome activation and downstream IL-1β production. These findings provide mechanistic insight and a therapeutic rationale for targeting MIF in subgroups of lupus patients, such as those classified as high genotypic MIF expressers or those with anti-snRNP antibodies.
PF-10a was feasible to implement in a diverse RA population. It strongly correlates with the HAQ but has fewer ceiling effects and is responsive to changes in RA disease activity, suggesting its validity for use in routine clinical practice.
The QUANTA Flash dsDNA assay showed good clinical performance in a large international multi-center study. Additionally, the strong correlation between anti-dsDNA antibody results and SLEDAI-2K scores supported the potential utility of QUANTA Flash dsDNA for monitoring disease activity.
Summary
Use of Patient-reported outcome measures (PROs) in rheumatology research is widespread, but use of PRO data to evaluate the quality of rheumatologic care delivered is less well established. This article reviews the use of PROs in assessing healthcare quality, and highlights challenges and opportunities specific to their use in rheumatology quality measurement. We first explore other countries’ experiences collecting and evaluating national PRO data to assess quality of care. We describe the current use of PROs as quality measures in rheumatology, and frame an agenda for future work supporting development of meaningful quality measures based on PROs.
Objective. Patient-reported outcomes (PROs) are an integral part of treat-to-target approaches in managing rheumatoid arthritis (RA). In clinical practice, however, routine collection, documentation, and discussion of PROs with patients are highly variable. The RISE LC (Rheumatology Informatics System for Effectiveness Learning Collaborative) was established to develop and share best practices in PRO collection and use across adult rheumatology practices in the United StatesMethods. The goals of the RISE LC were developed through site surveys and in-person meetings. Participants completed a baseline survey on PRO collection and use in their practices. RISE LC learning sessions focused on improving communication around PROs with patients and enhancing shared decision-making in treatment plans. During the coronavirus disease 2019 (COVID-19) pandemic, the RISE LC pivoted to adapt PRO tools for telehealth.Results. At baseline, all responding sites (n = 15) had established workflows for collecting PROs. Most sites used paper forms alone. PRO documentation in electronic health records was variable, with only half of the sites using structured data fields. To standardize and improve the use of PROs, participants iteratively developed a Clinical Disease Activity Index-based RA Disease Activity Communication Tool to solicit treatment goals and improve shared decision-making across sites. The COVID-19 pandemic necessitated developing a tool to gauge PROs via telehealth.Conclusion. The RISE LC is a continuous, structured method for implementing strategies to improve PRO collection and use in rheumatological care, initially adapting from the Learning Collaborative model and extending to include features of a learning network. Future directions include measuring the impact of standardized PRO collection and discussion on shared decision-making and RA outcomes.
BackgroundTreat-to-target is the recommended strategy for the management of rheumatoid arthritis (RA) and involves regular assessment of disease activity using validated measures and subsequent adjustment of medical therapy if patients are not in remission or low disease activity. Recommendations published in 2012 detailed the preferred disease activity measures but there have been few publications on implementation of disease activity measures in a real-world clinic setting.MethodsPlan-Do-Study-Act (PDSA) methodology was used over two cycles with a goal of increasing provider measurement of disease activity during all RA patient visits. In PDSA cycle 1, we implemented a paper-based form to help providers assess disease activity in RA patients. PDSA cycle 2 included the creation of separate patient and physician forms for collection of information, identification of patients prior to their clinic visit and incorporation of medical assistants into the workflow.ResultsThe first PDSA cycle improved the number of RA patients with documented disease activity measures from 24 % over a 4-week period, to an average of 44 % over an 8-week period. The second PDSA cycle showed a sustained and dramatic improvement, with 85 % of patients having a disease activity measure recorded over a 27-week period.ConclusionsImplementation of disease activity measurement in a typical academic rheumatology clinic can be achieved by standardizing workflow using a simple paper form.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-016-1633-x) contains supplementary material, which is available to authorized users.
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