scholarly journals Associations of serum soluble Fas and Fas ligand (FasL) with outcomes in systemic lupus erythematosus

2020 ◽  
Vol 7 (1) ◽  
pp. e000375
Author(s):  
Fabien B Vincent ◽  
Rangi Kandane-Rathnayake ◽  
Rachel Koelmeyer ◽  
James Harris ◽  
Alberta Y Hoi ◽  
...  

ObjectiveFas/Fas ligand (FasL) and B cell-activating factor (BAFF) signalling have pivotal roles in SLE pathogenesis. We investigated the clinical associations of serum concentrations of soluble Fas (sFas) and soluble FasL (sFasL) in SLE and their relationship with BAFF.MethodsSerum sFas and sFasL were quantified by multiplex assay, and BAFF by ELISA, in 118 patients with SLE and 17 healthy controls (HC). SLE disease activity and organ damage were assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics Damage Index.ResultssFas, sFasL and BAFF were detectable in all samples. Serum sFas and sFasL were significantly higher in SLE compared with HC. In univariable regression analyses, patients with active renal disease and those with flare had significantly higher levels of sFas compared with those without. High serum BAFF in patients with SLE was associated with increased sFas but not sFasL. The association between sFas and renal disease remained significant after adjusting for BAFF, but the association with flare attenuated. High sFas levels were associated with increased time-adjusted mean SLEDAI-2K, even after adjusting for BAFF, and with higher odds of flare over time. In contrast, high sFasL was associated with reduced organ damage over time. Serum sFasL/sFas ratio was negatively associated with active overall disease, flare and organ damage.ConclusionsSerum sFas is associated with active renal SLE, and active disease and flare over time, while sFasL/sFas ratio is negatively associated with disease activity and organ damage accrual. Treatments correcting abnormal levels of sFas/FasL may be worthy of evaluation in SLE.

2020 ◽  
Vol 9 (11) ◽  
pp. 3563
Author(s):  
Tomoyuki Asano ◽  
Naoki Matsuoka ◽  
Yuya Fujita ◽  
Haruki Matsumoto ◽  
Jumpei Temmoku ◽  
...  

Objective: T cell immunoglobulin and mucin-domain-containing molecule 3 (TIM-3) is implicated in the development of various autoimmune diseases. We aimed to investigate the levels of soluble TIM-3 (sTIM-3) and their associations between clinical parameters in patients with systemic lupus erythematosus (SLE). Methods: Serum samples were collected from 65 patients with SLE and 35 age-matched healthy controls (HCs). The SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI) were used to assess SLE disease activity and SLE-related organ damage. British Isles Lupus Assessment Group (BILAG)-2004 index was also used to assess SLE disease activity. Soluble TIM-3 (sTIM-3) in sera from patients with SLE and HCs were evaluated by enzyme-linked immunosorbent assay (ELISA). The results were compared with the clinical parameters of SLE including SLE disease activity. Results: Serum sTIM-3 levels in patients with SLE (median 2123 pg/mL (interquartile range (IQR), 229–7235)) were significantly higher than those in HCs (1363 pg/mL; IQR, 1097–1673; p = 0.0015). Serum levels of sTIM-3 were correlated with disease activity of SLE using the SLEDAI-2K score (p < 0.001, r = 0.53). The serum sTIM-3 levels in SLE patients with active renal disease (BILAG renal index A-B) were significantly higher than those without the active renal disease (BILAG renal index C–E). However, no significant difference was observed in serum sTIM-3 levels between SLE patients with and without active involvement in other organs (BILAG index). Serum sTIM-3 levels were significantly elevated in SLE patients with organ damage (2710 pg/mL; IQR, 256–7235) compared to those without organ damage (1532 pg/mL; IQR, 228–5274), as assessed by the SDI (p = 0.0102). Conclusions: Circulating sTIM-3 levels are elevated in SLE patients, and serum sTIM-3 levels are associated with SLE disease activity and SLE-related organ damage. The data indicate a possible link between the TIM-3/Gal-9 pathway and SLE clinical phenotypes, and further investigation of the TIM-3 pathway in SLE pathophysiology is warranted.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1059.3-1059
Author(s):  
M. Garabajiu ◽  
L. Mazur-Nicorici ◽  
T. Rotaru ◽  
V. Salaru ◽  
S. B. Victoria ◽  
...  

Background:Systemic lupus erythematosus is an autoimmune disease with a major impact on patient’s quality of life.Objectives:To evaluate patient’s attitude toward early disease and factors that influence it.Methods:Performed case-control study included SLE patients that fulfilled SLICC, 2012 classification criteria. The research included two groups of patients: early SLE – 1stgroup (disease duration ≤24 months) and non-early SLE – 2ndgroup control (disease duration >24 months). The pattern of the disease activity was assessed by patient global assessment (PGA), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus Activity Measure (SLAM), for SLE activity, SLICC/ACR Damage Index (DI) for disease irreversible changes and SF-8 for the Quality of Life (QoL).Results:A total of 101 SLE patients with 34 in the 1stgroup (early SLE) and 67 in the 2ndgroup (non-early SLE) was analyzed. The disease activity showed high disease activity in both groups by SLEDAI (7,02±4,16 and 6,26±4,43 points, p>0,05) and SLAM (7,47±4,40 and 7,31±4,10 points, p>0,05) such as (46,97±19,39 vs 47,98±22,41 points). The QoL was appreciated as low, by both components (mental and physical), in groups. The damage index was higher in the 2nd group (0,23±0,43 and 1,07±1,29, p<0,001), which can be explained by the development of irreversible changes with the increase of disease duration.The PGA in early SLE was influenced by subjective symptoms contained in SLAM index (r=0,48, p<0,05), such as fatigue and depression, and the level of the quality of life (r=0,65, p<0,001). Meantime, PGA in patients with longer disease duration (>2 years), was influenced by the presence of organ damage by SLICC/ACR DI (0,23, p<0,05) and objective findings of the disease activity contained in SLEDAI (r=0,33, p<0,005) and SLAM (0,44, p<0,001).Conclusion:The disease recognition in patients with early SLE was determined by subjective and psycho-emotional signs, while in patients with longer disease duration it was influenced by organ damage and complications.References:no referencesDisclosure of Interests:None declared


2010 ◽  
Vol 38 (1) ◽  
pp. 60-63 ◽  
Author(s):  
DOMINIQUE IBAÑEZ ◽  
DAFNA D. GLADMAN ◽  
ZAHI TOUMA ◽  
MANDANA NIKPOUR ◽  
MURRAY B. UROWITZ

Objective.Adjusted mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; AMS) measures lupus disease activity over time. Our aim was to determine optimal visit frequency for calculating AMS.Methods.Patients followed monthly for 12 consecutive visits were included. AMS was calculated using all of the SLEDAI 2000 (AMSGOLD using all 12 visits), only quarterly visits (AMS3, using visits 3 months apart), semiannual visits (AMS6, using first, middle, and last visits only), and annual visits (AMS12, using only the first and last visits). Comparisons of AMS3, AMS6, and AMS12 with AMSGOLD are made using descriptive statistics.Results.Seventy-eight patients were included (92% women, mean age at SLE diagnosis 30.1 yrs and at study start 46.2 yrs). The mean (SD) AMSGOLD for the entire year was 2.05 (1.66), for AMS3 1.99 (1.65), for AMS6 2.12 (1.87), and for AMS12 2.08 (1.83). Mean (SD) of the absolute differences with AMSGOLD: for AMS3 0.29 (0.33), for AMS6 0.45 (0.59), and for AMS12 0.61 (0.58). Differences that were < 0.5 were considered minimal while those ≥ 1 were deemed important. Comparing AMSGOLD to AMS3, 82% of the differences were minimal and 3% were important. When comparing to AMS6, 68% were minimal and 10% were important, while comparing to AMS12, 50% were minimal and 21% were important.Conclusion.Usual clinic visits occurring quarterly offer a good estimation of disease activity over a 1-year period and are preferred over semiannual and annual visits.


2018 ◽  
Vol 45 (8) ◽  
pp. 1136-1144 ◽  
Author(s):  
Anne Troldborg ◽  
Steffen Thiel ◽  
Marten Trendelenburg ◽  
Justa Friebus-Kardash ◽  
Josephine Nehring ◽  
...  

Objective.The pathogenesis of systemic lupus erythematosus (SLE) involves complement activation. Activation of complement through the classical pathway (CP) is well established. However, complement activation through pattern recognition not only happens through the CP, but also through the lectin pathway (LP). We investigated the hypothesis that the LP is activated in SLE and involved in the pathogenesis of the disease.Methods.Using immunoassays developed in-house, we measured concentrations of LP proteins in a cohort of 372 patients with SLE and 170 controls. We estimated complement activation measuring total C3, and investigated whether LP protein concentrations were associated with complement activation and disease activity. Protein changes and disease activity over time were assessed in a cohort of 52 patients with SLE followed with repeated samples over a 5-year period.Results.Concentrations of LP proteins in SLE were altered compared with controls. The differences observed in LP proteins associated with complement activation were reflected by a decrease in total C3. The pattern recognition molecules (M-ficolin, CL-L1, and CL-K1), the serine protease (MASP-3), and the associated protein (MAp19) displayed a negative correlation with disease activity. Changes in MASP-2 concentrations over time correlated significantly with increased disease activity. Association between active proteinuria and serum concentration was observed for MASP-3 and MAp19.Conclusion.In patients with SLE, we measured specific changes in LP proteins that are associated with complement activation and disease activity, indicating that the LP is activated in patients with SLE. These novel findings substantiate the involvement of the LP in SLE.


Lupus ◽  
1999 ◽  
Vol 8 (7) ◽  
pp. 508-513 ◽  
Author(s):  
P A Courtney ◽  
A D Crockard ◽  
K Williamson ◽  
J McConnell ◽  
R J Kennedy ◽  
...  

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