Serum soluble CD25 as a risk factor of renal impairment in systemic lupus erythematosus — a prospective cohort study

Lupus ◽  
2018 ◽  
Vol 27 (7) ◽  
pp. 1100-1106 ◽  
Author(s):  
R J Zhang ◽  
X Zhang ◽  
J Chen ◽  
M Shao ◽  
Y Yang ◽  
...  

Objective Serum soluble CD25 (sCD25) could be used as a biomarker for disease activity in conditions associated with T-cell activation including various autoimmune diseases. This study aimed to explore the role of sCD25 as an indicator of disease activity and organ involvement in patients with systemic lupus erythematosus (SLE). Methods Serum samples were collected from 107 SLE patients and 92 age-matched healthy controls (HCs). All patients were followed up for 24 weeks, and sCD25 was measured by enzyme-linked immunosorbent assay. Clinical and laboratory data were recorded at baseline and then every two weeks until week 24. The Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI)-2K was adopted for assessing disease activity at all visits. Results Serum sCD25 levels were significantly increased in SLE patients compared to those in HCs ( p < 0.001). More patients in the high-sCD25 group had lupus nephritis, arthritis and vasculitis ( p = 0.010, p = 0.023 and p = 0.042, respectively). SLEDAI-2K, erythrocyte sedimentation rate, C-reactive protein and 24-hour urinary protein excretion were all associated with high levels of sCD25 ( p < 0.001, p = 0.002, p = 0.038 and p = 0.029, respectively). During the 24-week follow-up, more patients in the high-sCD25 group developed renal impairment (48% vs 6.2%, p = 0.005), and higher levels of sCD25 ( p = 0.033) were found at the time of onset of renal disease. Conclusions Serum sCD25 is a hallmark of disease activity and a predictor of renal disease in patients with SLE.

2021 ◽  
Author(s):  
Miki Nakano ◽  
Masahiro Ayano ◽  
Kazuo Kushimoto ◽  
Shotaro Kawano ◽  
Kazuhiko Higashioka ◽  
...  

Abstract Background: CD226 is an activating receptor expressed on the cell surface of natural killer cells and T cells. A soluble form of CD226 (sCD226) is known to be shed from the membrane type of CD226 (mCD226). Although CD226 polymorphism and mCD226 are known to be involved in systemic lupus erythematosus (SLE), the involvement of sCD226 in SLE is still unknown. Therefore, we aimed to reveal the association of sCD226 with SLE.Methods: We measured serum sCD226 levels using an enzyme-linked immunosorbent assay in 58 SLE patients and 33 healthy controls (HCs) and evaluated their associations with SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, and laboratory data. We defined the maximum values of sCD226 in HCs as a cut-off level and compared the cumulative probability of flare for patients with high and low sCD226 levels. Results: Serum sCD226 levels showed no significant differences between SLE patients and HCs. However, sCD226 levels were significantly elevated in active SLE patients with a SLEDAI-2K score of ≥20 compared with HCs. In SLE patients, sCD226 levels were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers. Moreover, the cumulative probability of flare was markedly higher in patients with high sCD226 than in those with low sCD226. In patients with neuropsychiatric involvement, sCD226 levels were elevated and reflected neuropsychiatric disease activity. Conclusion: Serum sCD226 levels were associated with disease activity and flares of SLE. Thus, it may be a useful biomarker for SLE, and its monitoring allows for more precise SLE management.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miki Nakano ◽  
Masahiro Ayano ◽  
Kazuo Kushimoto ◽  
Shotaro Kawano ◽  
Kazuhiko Higashioka ◽  
...  

AbstractCD226 is an activating receptor expressed on the cell surface of natural killer cells and T cells. Although CD226 polymorphism is known to be involved in systemic lupus erythematosus (SLE), the involvement of soluble CD226 (sCD226) in SLE is still unknown. In the present study, we measured serum sCD226 levels using an enzyme-linked immunosorbent assay in 58 SLE patients and 33 healthy controls (HCs) and evaluated their associations with SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, laboratory data, and the cumulative probability of flare. Serum sCD226 levels showed no significant differences between SLE patients and HCs. However, sCD226 levels were significantly elevated in active SLE patients with a SLEDAI-2K score of ≥ 20 compared with HCs. In SLE patients, sCD226 levels were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers. Moreover, the cumulative probability of flare was markedly higher in patients with high sCD226 than in those with low sCD226. In patients with neuropsychiatric involvement, sCD226 levels were elevated and reflected neuropsychiatric disease activity. These findings indicate that serum sCD226 levels are associated with disease activity and flares of SLE. Thus, it may be a useful biomarker for SLE, and its monitoring allows for more precise SLE management.


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.


2021 ◽  
Vol 10 (20) ◽  
pp. 4788
Author(s):  
Katarzyna Pawlak-Buś ◽  
Wiktor Schmidt ◽  
Piotr Leszczyński

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the production of multiple autoantibodies, resulting in tissue and organ damage. Recent studies have revealed that interleukin-23 (IL-23) and interleukin-27 (IL-27) may be therapeutically relevant in selected SLE manifestations. This study aimed to identify associations between serum IL-27 and IL-23 levels and disease activity in Polish patients with different manifestations of SLE: neuropsychiatric lupus (NPSLE), and lupus nephritis (LN). Associations between interleukin levels and oligo-specific antibodies against double-stranded DNA (dsDNA), dose of glucocorticoids, and type of treatment were also analyzed. An enzyme-linked immunosorbent assay was used to assess anti-dsDNA antibodies and analyze the serum concentration of IL-27 and IL-23 from 72 patients aged 19–74 years with confirmed active SLE. Disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2-K). No significant correlations between interleukin levels and SLEDAI score, anti-dsDNA, corticosteroid dose, or type of treatment were noted. Patients with NPSLE and LN presented the highest median scores of SLEDAI.


Lupus ◽  
2020 ◽  
Vol 29 (13) ◽  
pp. 1781-1789
Author(s):  
Suhas K Ganguli ◽  
Joyce S Hui-Yuen ◽  
Meenakshi Jolly ◽  
Jane Cerise ◽  
Barbara Anne Eberhard

Objective To evaluate the reliability, validity, feasibility and psychometric performance of the Lupus Impact Tracker (LIT) as a patient reported outcome (PRO) measure tool in pediatric systemic lupus erythematosus (pSLE). Methods This is a prospective, observational, pilot study where patients aged between 12 and 25 years, fulfilling the 1997 ACR classification criteria for SLE, were enrolled. Over 3 consecutive, routine, clinical visits, the patients completed the LIT alongside the Patient-Reported Outcomes Measurement Information System-Short Forms (PROMIS-SFs), Childhood Health Assessment Questionnaire (CHAQ). Rheumatologists completed the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC-ACR) Damage Index. Demographic, clinical and laboratory data were also collected. Results Of 46 patients enrolled, 38 patients completed 2 visits and 31 completed all 3 visits. Seventy-eight percent were female, 33% African American, 28% Asian, 15% Caucasian and 17% Hispanic. The mean (SD) age was 17.2 (2.7) years, with a mean (SD) disease duration of 4.6 (3.1) years. The mean (SD) SLEDAI-2K at enrollment was 3.54 (2.96). In the 38 patients who completed two or more visits, intra-class correlation coefficient and Cronbach alpha were calculated to be 0.70 and 0.91 respectively, signifying good reliability of LIT. The LIT showed positive correlation with CHAQ-Disability Index and majority of the PROMIS-SFs parameters. Construct validity was established against clinical disease activity (SLEDAI-2K). Conclusion The preliminary results indicate that the LIT is a reliable and valid instrument to capture PRO in p-SLE. Prospective validation with a larger, multicenter cohort is the next step.


Lupus ◽  
2011 ◽  
Vol 20 (14) ◽  
pp. 1494-1500 ◽  
Author(s):  
Z Rezaieyazdi ◽  
M Sahebari ◽  
MR Hatef ◽  
B Abbasi ◽  
H Rafatpanah ◽  
...  

The role of C-reactive protein (CRP) in systemic lupus erythematosus (SLE) as an inflammatory marker is still controversial. Recently, more sensitive methods, such as high sensitive CRP (hs-CRP) have been used to detect micro-inflammation. The role of hs-CRP in lupus flare has not been documented well. We conducted this study to examine the correlation between hs-CRP serum concentrations and disease activity in lupus. Ninety-two SLE patients and 49 healthy controls contributed to our study. Most confounding factors influencing the hs-CRP values were excluded. Disease activity was estimated using the SLE Disease Activity Index (SLEDAI-2K). hs-CRP values were determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum values of hs-CRP were significantly higher ( p < 0.001, z = 3.29) in patients compared with healthy controls. The cutoff point for hs-CRP between patients and controls was 0.93 mg/L (Youden’s Index = 0.39). There was no correlation between hs-CRP serum levels and disease activity. Furthermore, hs-CRP values did not correlate with any of the laboratory parameters, except for C3 ( p = 0.003, rs = −0.2) and C4 ( p = 0.02, rs = −0.1). Although hs-CRP serum levels were significantly higher in lupus patients compared with healthy controls, it seems that this marker is not a good indicator for disease activity.


2020 ◽  
Author(s):  
Zhuochao Zhou ◽  
Aining Xu ◽  
Jialin Teng ◽  
Fan Wang ◽  
Yun Tan ◽  
...  

Abstract Backgroud: To investigate the role of Tyro3 receptor in macrophages’ efferocytosis of apoptotic cells in systemic lupus erythematosus (SLE), we aimed to reveal the clinical relevance and impact of anti-Tyro3 antibody on SLE. Methods : The serum levels of IgG-type autoantibody against Tyro3 receptor were detected in new-onset, treatment-naïve SLE patients (n =70) and healthy controls (HCs) (n =70) using enzyme-linked immunosorbent assay (ELISA). The correlation of the levels of autoantibodies against Tyro3 receptor with clinical and laboratory characteristics were analyzed by Spearman correlation analysis. Receiver operating characteristic (ROC) curve was used to assess the sensitivity and specificity of anti-Tyro3 IgG for the diagnosis of SLE. The effects of purified Tyro3 autoantibody from SLE patients on the efferocytosis of human monocyte-derived macrophages were measured by flow cytometry and immunofluorescence. Results : The serum levels of IgG-type autoantibody against Tyro3 receptor were significantly elevated in patients with SLE compared to HCs ( p < 0.0001). The levels of anti-Tyro3 IgG were negatively associated with haemoglobin (Hb) ( r =-0.294, p = 0.014), and positively correlated with the presence of oral ulcers ( r = 0.254, p = 0.034), SLE disease activity index (SLEDAI) score ( r = 0.254, p = 0.034), erythrocyte sedimentation rate (ESR) ( r = 0.430, p = 0.000), C-reactive protein (CRP) ( r = 0.246, p = 0.049) and immunoglobulin G (IgG) ( r = 0.408, p = 0.001). Higher levels of anti-Tyro3 antibody were observed in patients with oral ulcers than paitents without oral ulcers ( p = 0.035). Further flow cytometry demonstrated that purified anti-Tyro3 IgG inhibited the efferocytosis of macrophages ( p = 0.004). Immunofluorescence assay also showed a decreased engulfment of apoptotic cells in the macrophages incubated with purified anti-Tyro3 IgG ( p = 0.044) compared with control IgG. Conclusions: These observations indicated that autoantibody against Tyro3 was associated with disease activity and impaired efferocytosis of macrophages, which might be involved in the pathogenesis of SLE.


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