ObjectivesThis article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögren's syndrome (pSS).MethodsBlood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels.Results14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines—interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α (p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022)—were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy.ConclusionsCytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.
ObjectivesPrimary Sjögren's syndrome (pSS) shares clinical features and pathogenetic mechanisms with systemic lupus erythematosus (SLE). SLE is associated with an increased thromboembolic risk; however, it is unclear whether pSS patients are susceptible to thromboembolic diseases. In this study, we examined ex vivo blood clot formation (clot strength, rates of clot formation and lysis) in pSS using thromboelastography (TEG) and platelet aggregation to common agonists using multiple electrode aggregometry (MEA). We also investigated the relationship between TEG/MEA parameters and clinical/laboratory features of pSS.DesignCase control.SettingSecondary care, single centre.Participants34 pSS patients, 11 SLE patients and 13 healthy volunteers (all women) entered and completed the study.Primary and secondary outcome measuresPrimary outcomes: TEG and MEA parameters between three subject groups. Secondary outcomes: The relationships between TEG/MEA and clinical/laboratory parameters analysed using bivariate correlation analysis with corrections for multiple testing.ResultsAll TEG and MEA parameters were similar for the three subject groups. After corrections for multiple testing, interleukin (IL)-1α and Macrophage inflammatory proteins (MIP)-1α remain correlated inversely with clot strength (r=−0.686, p=0.024 and r=−0.730, p=0.012, respectively) and overall coagulability (r=−0.640, p=0.048 and r=−0.648, p=0.048). Stepwise regression analysis revealed that several cytokines such as MIP-1α, IL-17a, IL-1α and Interferon (IFN)-γ may be key predictors of clot strength and overall coagulability in pSS.ConclusionsClot kinetics and platelet receptor function are normal in pSS. Several cytokines correlate with clot strength and overall coagulability in pSS.
BackgroundPrimary Sjögren's syndrome (pSS) is an autoimmune rheumatic disease affecting the exocrine glands. Several pSS-associated clinical and laboratory parameters may predispose to thromboembolic risk, however clinical data is conflicting.My primary objective was to test whether whole blood clot formation is abnormal in pSS using several complementary approaches: Thromboelestrography (TEG) and Multiplate platelet mapping (MPP) for pSS patients compared to healthy and disease (lupus-SLE) controls and compare the size/composition of blood clots formed ex-vivo between pSS patients and healthy controls using a clotting chamber, which simulates the clotting process in-vivo.My secondary objectives were to determine if any clinical/laboratory/cytokine parameters were associated with abnormal clotting. MethodsTEG and MPP were performed on blood samples from 12 healthy controls, 24 pSS and 11 SLE patients.For TEG: clot formation speed, strength and lysis rate were analysed. For MPP, platelet receptor responses to common agonists were investigated.12 pSS patients completed a clotting chamber procedure.Univariate correlation analysis was used to determine the relationship between clotting and clinical/laboratory/ cytokine parameters. ResultsAll TEG and MPP parameters were similar between groups. Statistically significant correlations were found for (a) ESR and clot lysis parameters (p<0.007); (b) CD40L and clot formation/lysis rate (P<0.01).Analysis of clot specimens from the clotting chamber is on-going. Preliminary data indicate that several cytokines are "consumed" during the clot formation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.