BackgroundTo date a complete characterization of the components of the complement (C) pathways (CLassical, LEctin and ALternative) in patients with systemic lupus erythematosus (SLE) has not been performed. We aimed to assess the function of these three C cascades through functional assays and the measurement of individual C proteins. We then studied how they relate to clinical characteristics.MethodsNew generation functional assays of the three pathways of the C system were assessed in 284 patients with SLE. Linear regression analysis was performed to study the relationship between the activity, severity, and damage of the disease and C system.ResultsLower values of the functional tests AL and LE were more frequent than those of the CL pathway. Clinical activity was not related to inferior values of C routes functional assays. The presence of increased DNA binding was negatively linked to all three C pathways and products, except for C1-inh and C3a which were positively related. Disease damage revealed a consistent positive, rather than a negative, relationship with pathways and C elements. Anti-ribosomes and anti-nucleosomes were the autoantibodies that showed a greater relationship with C activation, mainly due to the LE and CL pathways. Regarding antiphospholipid antibodies, the most related with C activation were IgG anti-β2GP, predominantly involving the AL pathway.ConclusionNot only the CL route, but also the AL and LE are related to SLE features. C expression patterns are linked to disease profiles. While accrual damage was associated with higher functional tests of C pathways, anti-DNA, anti-ribosomes and anti-nucleosomes antibodies, were the ones that showed a higher relationship with C activation, mainly due to the LE and CL pathways.
Introduction. The diagnostic value of salivary gland scintigraphy (SGS) in Sjögren's syndrome (SS) is not completely known. Whether qualitative or quantitative methods of SGS interpretation are the most appropriate remains a matter of debate. We sought to determine whether the diagnostic discrimination of quantitative excretion fraction is higher compared to SGS qualitative visual analysis in a cohort of subjects with suspected SS. Materials and methods. Cross-sectional study that encompassed 204 subjects who underwent SGS for potential SS diagnosis. Based on clinical judgement, three groups were established: SS, non-SS autoimmune diseases (AID non-SS) and neither SS nor other AID (non-AID). In addition, American-European Consensus Group -AECG-and American College of Rheumatology -ACR-criteria were applied. Qualitative diagnosis through visual analysis -normal vs. abnormal and Schall's classi cation grade-and semiquantitative and quantitative excretion fraction (EF%) scores were established following SGS assessment. The diagnostic discrimination of the different SGS scores for the various SS diagnostic modalities (clinical judgement and AECG and ACR criteria) was compared through their areas under the curve (AUC).Results. Most SGS parameters were signi cantly associated with SS-related clinical and laboratory features. Schall's grade ≥ III was signi cantly more frequent in SS than in non-SS patients. In general, EF%-derived parameters did not show signi cant differences between groups. AUC of Schall's classi cation reached statistical signi cance in its diagnostic discrimination for SS clinical judgement (AUC 0.704 [95%CI 0.597-0.811], p = 0.000) and AECG criteria (AUC 0.764 [95%CI 0.641-0.886], p = 0.000). Similarly the EF% submandibular mean (AUC 0.737 [95%CI 0.546-0.931] p = 0.032) was signi cantly associated with SS diagnosis through ACR criteria. However, AUC comparisons between qualitative and quantitative methods did not yield signi cant values.Conclusion. SS diagnostic discrimination of EF% is not superior to that obtained by qualitative visual analysis.
Transforming growth factor beta (TGF-β) is a highly pleiotropic cytokine that has broad anti-inflammatory and immunosuppressive effects. In patients with systemic lupus erythematosus (SLE), the immunosuppressive effect of TGF-β1 is thought to be dysfunctional. In the present work, we aimed to study the relationship between the serum levels of TGF-β1 with the characteristics of the disease as well as with the patterns of activity, damage, or severity of the disease. Two hundred and eighty-four patients with well-characterized SLE were recruited. The serum levels of TGF-β1 were assessed. A multivariable linear regression analysis was performed to analyze the relation of disease characteristics to TGF-β1. The Katz severity index (beta coefficient 179 [95% confidence interval 7–350] pg/mL, p = 0.041) and SLEDAI activity index (beta coefficient 96 [95% CI 20–171] pg/mL, p = 0.014) were associated with higher serum levels of TGF-β1 after the multivariable analysis. When the disease-specific features were studied, ocular and cardiovascular manifestations were positively associated with serum TGF-β1 levels. In contrast, gastrointestinal and musculoskeletal involvements were associated with lower levels of circulating TGF-β1. Among patients with SLE, the serum levels of TGF-β1 were highly associated with disease-related manifestations.
Background Transforming growth factor beta (TGF-β1) is a multifunctional cytokine that has anti-inflammatory and immunosuppressive effects. TGF-β1 has been linked to cardiovascular disease in the general population. The immunosuppressive effect of TGF-β1 is believed to be dysregulated in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to study the relationship of serum levels of TGF-β1 with subclinical carotid atherosclerosis in patients with SLE. Methods The study included 284 patients with SLE. Serum levels of TGF-β1 and subclinical carotid atherosclerosis (by carotid ultrasonography) were evaluated. In addition, the complete lipid profile and insulin resistance were analyzed. Multivariable linear and logistic regression analysis was performed to establish the relationship of TGF-β1 with carotid subclinical atherosclerosis adjusting for traditional cardiovascular risk factors that included lipid profile and insulin resistance. Results Circulating TGF-β1 was positively and significantly associated with higher levels of LDL:HDL cholesterol ratio and atherogenic index. TGF-β1 was also associated with significantly lower levels of HDL cholesterol and apolipoprotein A1. Remarkably, TGF-β1 was associated with the presence of carotid plaque not only after adjustment for demographics (age, sex, body mass index, diabetes, hypertension, and aspirin use) but also after adjustment for relationships of TGF-β1 with lipid profile molecules, insulin resistance, and SLEDAI disease score (odds ratio 1.14 [95% confidence interval 1.003–1.30], p = 0.045). Conclusion TGF-β1 serum levels are positively and independently associated with the presence of subclinical atherosclerosis disease in patients with SLE.
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