These data confirm the importance of family history as a significant risk factor for the development of Type 1 diabetes and support the hypothesis that the common autoimmune diseases share at least some aetiological mechanisms.
Objective Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder known for its broad clinical spectrum. Recently, the European, British and Latin American rheumatology professional societies (EULAR, BSR and PANLAR) published updated recommendations for SLE management. The objective of this study was to characterize the data supporting the updated recommendations, with the goal of highlighting areas which could benefit from additional high-quality research. Methods References were compiled from the recently published EULAR, BSR and PANLAR SLE treatment recommendations. Data collected from each study included publication year, treatment regimen, study design, sample size, inclusion and exclusion criteria and relevant SLE diagnostic criteria. Studies with less than 10 patients and those which did not specify the SLE diagnostic criteria used were excluded. Results Altogether 250 studies were included in this study. The majority were prospective and retrospective cohorts (72%), with only a small percentage of randomized controlled trials (28%). The median number of patients included was 37 (IQR 19-86). The revised American College of Rheumatology (ACR) 1982 criteria were the most commonly used criteria for SLE diagnosis (52%), followed by the revised ACR criteria from 1997 (27%). Only a small proportion of studies included the use of disease activity scores when defining study population (15%). Conclusions Our study has indicated a scarcity of sufficiently powered high-quality research referenced in the recently published SLE treatment guidelines. Well-designed large-scale studies utilizing the updated 2019 SLE diagnostic criteria are needed to better inform healthcare professionals caring for patients with SLE.
Acute kidney injury (AKI) is characterized by cell death and inflammation. CD24 is a protein induced during tissue damage and is not expressed in mature renal tissue. We explored the role of CD24 in the pathogenesis of folic acid-induced AKI (FA-AKI) in mice. A single Intraperitoneal (IP) injection of folic acid induced AKI in WT and CD24−/− mice. Renal function tests, histological analysis, immunohistochemistry, Western blot analysis, and ELISA were performed to assess the severity of renal damage and the intensity of the inflammatory response. FA-AKI induced CD24 in the distal tubular epithelial cells. Compared to WT mice, FA-AKI CD24−/− mice exhibited an attenuated reduction in renal function and histological injury, lower serum IL-10 and interferon γ, and decreased expression of renal TNFα. In contrast, renal and systemic IL-33 upregulation were augmented. CD24−/− FA-AKI animals exhibited increased splenic margination and renal infiltration of regulatory T cells (Tregs). At day 7, FA-AKI CD24−/− mice exhibited increased expression of tubular pro-apoptotic and decreased anti-apoptotic proteins compared to WT animals. Anti-CD24 antibody administration to FA-AKI mice attenuated the decrease in renal function as well as the histological injury. Renal biopsies from patients with ATN stained strongly for CD24 in the distal tubules. In conclusion, during AKI, upregulation of CD24 promotes renal inflammation through inhibition of Treg infiltration and diversion of cell death towards necrosis rather than apoptosis. Neutralization of CD24 may prove a target for future therapies in AKI.
Background:Anti-IL17 agents, such as Secukinumab (SEC) and Ixekizumab (IXE) have been shown to be efficacious for the treatment of psoriasis and PsA12. In the field of psoriasis, there is growing evidence of a successful switching between the two anti-IL-17 agents in case of an insufficient response to one of the treatments3 There is no information on the efficacy of switching between anti IL17 agents in PsA.Objectives:To assess the clinical response to IXE in patients with PsA following SEC failure.Methods:A retrospective observational study was conducted in two rheumatology centers in Israel, including PsA patients with a history of treatment with SEC, further treated with IXE for a minimum of 3 months. Lack of efficacy, loss of efficacy, and side effects over time were reported as a reason for switching to another anti-IL17 agent. The mean difference between the beginning of the follow up period and the different follow up points (6 and 12 months) was tested using a one-sample t-test. Time until treatment failure was estimated using Kaplan–Meier curves, and compared using the log-rank test. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated using the Cox proportional-hazards model to test the association between each variable and the time to treatment failure.Results:The study included 23 PsA patients (11♀/12♂), mean age 58.7 years±13.4 SD. Most patients (n=20, 86%) received 2+ TNFi and 10 patients (43%) received both TNFi and ustekinumab. Median number of biologics prior to SEC was 3 (IQR 2-4). There was a significant improvement in TJC at 6 and 12 months (-2.16 [-4.0, -0.3]; p=0.025 and-1.69 [-3.09, -0.28]; p=0.022, respectively). SJC was significantly improved at 6 months but not at 12 months (-2.68 [-5.3, -0.04]; p= 0.046 and -1.50 [-4.25,1.25]; p=0.26, respectively). CDAI score was significantly improved at 6 months (-10.19, [-16.26, -4.1], p=0.002) and at 12 months (-9.29 [-14.8, -3.71], p=0.003) as was SDAI score (-10.13 [-16.4, -3.8], p=0.003 and -12.2 [-17.1, -7.2], p=0.0002). At six months, PASI50 was achieved by 81% (13 patients), PASI75 was achieved by 63% (10 patients), PASI90 was achieved by 50% (8 patients) and PASI100 by 31% (10 patients). At 12 months, PASI50 and PASI75 was achieved by 57% (8 patients), PASI90 was achieved by 43% (6 patients) and PASI100 by 21% (3 patients).Over time, of the 23 patients treated with IXE, 15 patients (65%) had experienced treatment failure, with a median treatment period of 8 months (IQR 6.5-13.5), of which 4 (17%) had primary treatment failure and 11 patients (48%) secondary treatment failure. Reasons for treatment cessation were: worsening psoriasis (4 patients (27%)), worsening peripheral arthritis (4 patients (27%)), both (7 patients (47%)), worsening of axial disease (2 patients (13%)) and adverse events (1 patient, 6%).Conclusion:patients after failure of multiple biologic treatments experienced significant response of peripheral arthritis and dermatologic disease on IXE after they had previously failed SEC. . However, in this refractory cohort of PsA, the effect was limited on time with 65% failure after a median time of 8 months.Within class switch from SEC to IXE is a plausible therapeutic option in PsA patients following secukinumab failure.References:[1]Mease PJ, McInnes IB, Kirkham B, et al. N Engl J Med. 2015;373(14):1329-1339.[2]Nash P, Kirkham B, Okada M, et al. Lancet Lond Engl. 2017;389(10086):2317-2327.[3]Bokor-Billmann T, Schäkel K. J Dermatol Treat. 2019;30(3):216-220Disclosure of Interests:None declared.
BackgroundAccurate measurement of patient reported outcomes (PROs) is important in systemic lupus erythematosus (SLE), a heterogeneous disease in which similar symptoms can have disparate impact across patients. PROMIS offers dynamic computer adaptive tests (CATs) to precisely and efficiently measure PROs in a variety of relevant domains.ObjectivesThe aims of this study were to: 1) assess the feasibility of administering PROMIS CATS serially to SLE outpatients 2) correlate PROMIS CATs with legacy PRO measures, SLE disease activity and organ damage 3) assess retest reliability of PROMIS CATs.MethodsAdults meeting American College of Rheumatology SLE classification criteria were recruited from a SLE Center of Excellence. Subjects completed the Short Form-36 (SF-36), LupusQoL-US, and selected PROMIS CATs. SLE disease activity, flare, and damage were evaluated with the SELENA-SLEDAI and SLICC-ACR damage index. PROMIS domains were compared with disease activity, damage, and similar domains in legacy instruments using Spearman correlations. Retest reliability was evaluated among subjects reporting stable SLE activity at two assessments one week apart using intraclass correlation coefficients (ICC).ResultsOf 198 patients approached, 163 (82%) completed at least one assessment, 130 (80%) completing it remotely. 138 (85%) completed a retest. Most PROMIS domains showed moderate to strong correlations with similar domains in both legacy instruments (Figure 1). However, correlations between PROMIS and the physician global assessment, SELENA-SLEDAI, and SLICC-ACR damage index were generally weak and statistically insignificant. PROMIS CAT retest ICCs ranged from 0.74 to 0.89.ConclusionsTo our knowledge, these data are the first to show that PROMIS CATs can be successfully administered to a diverse cohort of SLE patients at the point of care or remotely, and are valid and reliable for many SLE relevant domains. Importantly, PROMIS scores did not correlate well with physician-derived measures. This disconnect between objective signs and symptoms and the subjective patient disease experience underscores the crucial need to integrate PROs into clinical care to ensure optimal disease management.AcknowledgementFunding for this study was provided by the Rheumatology Research Foundation Scientist Development Award.Disclosure of InterestNone declared
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