scholarly journals Association of elevated serum soluble CD226 levels with the disease activity and flares of systemic lupus erythematosus

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.

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 12 ◽  
Author(s):  
Miki Nakano ◽  
Masahiro Ayano ◽  
Kazuo Kushimoto ◽  
Shotaro Kawano ◽  
Kazuhiko Higashioka ◽  
...  

BackgroundCD226, an activating receptor expressed on the surface of natural killer (NK) cells and T cells, is also seen on B cells and CD226 polymorphism is associated with systemic lupus erythematosus (SLE). Because the specific roles of CD226+ B cells in SLE are still unknown, we investigated the association of CD226+ B cells with SLE.MethodsWe measured CD226 expression on B cells and its subsets using flow cytometry in 48 SLE patients and 24 healthy controls (HCs). We assessed the relationships between CD226+ B cells and SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, laboratory data, and prognosis after 12 months.ResultsThe proportions of CD226+ cells in whole B cells and all its subsets were significantly higher in SLE patients than HCs. In SLE patients, the proportions of CD226+ B cells and CD226+ switched-memory (SM) B cells were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers, and negatively correlated with serum complement levels. Moreover, basal percentages of CD226+ B cells and CD226+ SM B cells were low in patients who were in Lupus Low Disease Activity State after 12 months. In patients with renal involvement, the proportion of CD226+ B cells increased. Additionally, the proportion of CD226+ B cells was higher in patients who were not in complete renal remission after 12 months.ConclusionsIncreased proportion of CD226+ B cells was associated with disease activity and prognosis of SLE. CD226+ B cells may be a useful biomarker for the management of SLE.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Wook-Young Baek ◽  
Ji-Min Woo ◽  
Hyoun-Ah Kim ◽  
Ju-Yang Jung ◽  
Chang-Hee Suh

AbstractSystemic lupus erythematosus (SLE) is characterized by impaired clearance of apoptotic cells. Milk fat globule epidermal growth factor 8 (MFGE8) is a protein that connects αvβ3 integrin on phagocytic macrophages with phosphatidylserine on apoptotic cells. We investigated whether genetic variation of the MFGE8 gene and serum MFGE8 concentration are associated with SLE. Single nucleotide polymorphisms (SNPs) were genotyped and serum concentrations were analyzed. The rs2271715 C allele and rs3743388 G allele showed higher frequency in SLE than in healthy subjects (HSs). Three haplotypes were found among 4 SNPs (rs4945, rs1878327, rs2271715, and rs3743388): AACG, CGCG, and CGTC. CGCG haplotype was significantly more common in SLE than in HSs. rs4945 was associated with the erythrocyte sedimentation rate and rs1878327 was associated with alopecia, C-reactive protein, complement 3, anti-dsDNA antibody, and high disease activity. rs2271715 and rs3743388 were associated with renal disease, cumulative glucocorticoid dose, and cyclophosphamide and mycophenolate mofetil use. Serum MFGE8 concentrations were significantly higher in SLE than in HSs. Furthermore, the levels of MFGE8 were significantly higher in SLE than HSs of the rs2271715 CC genotype. In conclusion, MFGE8 genetic polymorphisms are associated not only with susceptibility to SLE but also with disease activity through modulation of gene expression.


Lupus ◽  
2019 ◽  
Vol 28 (12) ◽  
pp. 1387-1396 ◽  
Author(s):  
W Yuan ◽  
H Cao ◽  
P Wan ◽  
R Shi ◽  
S Zhou ◽  
...  

Background This study evaluated the diagnostic performances of total and high-avidity (HA) anti-dsDNA enzyme immunoassays (EIA) in Chinese systemic lupus erythematosus (SLE) patients. Methods A total of 410 serum samples from 217 SLE patients, 54 patients with other systemic autoimmune diseases, and 139 healthy subjects were tested on total and HA anti-dsDNA EIA, as well as three commercial in vitro diagnostic kits: BioPlex 2200 ANA Screen, Kallestad anti-dsDNA EIA, and Crithidia Lucilae IFA. The disease activities of SLE patients were assessed using the modified SLE Disease Activity Index. The diagnostic performances of each assay were analyzed using Analyse-it software. Results The diagnostic performances of the total and HA anti-dsDNA EIA kits were comparable to other commercially available in vitro diagnostic assays. Receiver operating characteristic curve analysis demonstrated an area under the curve ranging from 0.85 to 0.89, with the total anti-dsDNA kit demonstrating the highest sensitivity and the HA kit showing higher specificity. An overall agreement of >90% was observed between the total and HA anti-dsDNA EIA kits and commercially available quantitative anti-dsDNA kits. The ratio of HA to total anti-dsDNA antibody was significantly higher among SLE patients with active disease status and/or kidney damage. All assays exhibited a significant correlation with disease activity and multiple clinical manifestations. Conclusions While the clinical performances of various anti-dsDNA assays showed adequate agreements, the BioPlex 2200 anti-dsDNA assay demonstrated the highest positive likelihood ratio and odds ratio. The HA anti-dsDNA EIA kit in association with the total anti-dsDNA kit provided superior performance in SLE diagnosis and monitoring disease activity.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Lei Gu ◽  
Lingxiao Xu ◽  
Xiaojun Zhang ◽  
Wenfeng Tan ◽  
Hong Wang ◽  
...  

The aim of this paper is to investigate the correlation of glucocorticoid-induced tumor necrosis factor receptor- (TNFR-) related protein ligand (GITRL) with disease activity and organ involvement in patients with systemic lupus erythematosus (SLE). Serum GITRL levels were measured in 58 patients with SLE and 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of serum GITRL levels with SLEDAI, laboratory values, and clinical manifestations were assessed. Serum GITRL levels were determined by ELISA. Serum GITRL levels were markedly increased in patients with SLE compared with healthy controls (mean 401.3 ng/mL and 36.59 ng/mL, resp.;P<0.0001). SLE patients with active disease showed higher serum GITRL levels compared to those with inactive disease (mean 403.3 ng/mL and 136.3 ng/mL, resp;P=0.0043) as well as normal controls (36.59 ng/mL;P<0.0001). Serum GITRL levels were positively correlated with SLEDAI, titers of anti-dsDNA antibody, erythrocyte sedimentation rate (ESR), and IgM and negatively correlated with complement3 (C3). Serum GITRL levels were higher in SLE patients with renal involvement and vasculitis compared with patients without the above-mentioned manifestations.


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.


Lupus ◽  
2020 ◽  
Vol 29 (11) ◽  
pp. 1346-1352
Author(s):  
Min Li ◽  
Gong Cheng ◽  
Zongyi Wang ◽  
Wen Liu ◽  
Yuebo Jin ◽  
...  

Objectives Lupus fundus abnormalities are a sight-threatening complication of systemic lupus erythematosus (SLE) and its pathogenesis remains to be studied. The aim of this study was to assess the clinical characteristics associated with the presence of anti-recoverin antibodies in patients with SLE, especially those with fundus abnormalities. Methods Seventy-six participants were enrolled, including 21 patients with fundus abnormalities (fundus group), 30 patients without fundus abnormalities (non-fundus group) and 25 healthy individuals. Serum anti-recoverin antibody levels were measured using enzyme-linked immunosorbent assay, and clinical and laboratory data were obtained from medical records. Results Compared with the non-fundus group, the fundus group had a higher incidence of hematuria ( p < 0.05). The Systemic Erythematosus Disease Activity Index (SLEDAI) score in the fundus group was significantly higher than the non-fundus group (21.48 ± 8.06 versus 10.80 ± 5.74, p < 0.001). The levels of serum anti-recoverin antibodies in the fundus group were significantly higher than the non-fundus group ( p = 0.029) or the healthy control group ( p = 0.011). Anti-recoverin-negative and -positive patients differed on a number of clinical parameters, including incidence of fever, rash, antinuclear antibody, anti-dsDNA antibody, erythrocyte sedimentation rate, immunoglobulin G, complement C3 and complement C4. The average SLEDAI score of anti-recoverin-positive patients was significantly higher than anti-recoverin-negative patients (17.73 ± 8.11 versus 12.56 ± 8.37, p < 0.05). Conclusions Anti-recoverin antibodies were related to higher disease activities in SLE, especially those with fundus abnormalities, suggesting that anti-recoverin antibodies may play an important role in the pathogenesis of fundus abnormalities in SLE.


2014 ◽  
Vol 42 (2) ◽  
pp. 202-209 ◽  
Author(s):  
Ki-Jo Kim ◽  
Ji-Young Kim ◽  
In-Woon Baek ◽  
Wan-Uk Kim ◽  
Chul-Soo Cho

Objective.Syndecan-1 (SDC-1) is a major constituent of the endothelial glycocalyx, which plays a role in maintaining vascular homeostasis and functions as a glomerular filtration barrier. SDC-1 is readily shed into the blood under various conditions, but the clinical implication of circulating SDC-1 in patients with systemic lupus erythematosus (SLE) remains unclear. We aimed to investigate the association of serum SDC-1 level with certain clinical manifestations of SLE.Methods.We measured serum SDC-1 levels by ELISA in 111 patients with SLE, 18 with rheumatoid arthritis (RA), and 20 healthy subjects, and investigated its association with clinical manifestations and laboratory variables.Results.Serum SDC-1 levels were higher in patients with SLE than in those with RA and healthy controls (both p < 0.001) and were positively correlated with SLE Disease Activity Index (SLEDAI; r = 0.367, p < 0.001) and anti-dsDNA antibody level (r = 0.259, p = 0.007), but inversely correlated with serum C3 and CH50 levels (r = −0.305, p = 0.001 and r = −0.244, p = 0.012). Patients with active nephritis had higher serum SDC-1 levels than patients with inactive nephritis and those without nephritis (both p < 0.001). In addition, serum SDC-1 levels were correlated with renal SLEDAI score (r = 0.540, p < 0.001) and excretion of proteinuria as measured by spot urine protein/creatinine ratio (r = 0.538, p < 0.001). In 14 patients with lupus nephritis (LN) whose serum samples were obtained at the time of renal biopsy, there was a positive correlation between serum SDC-1 levels and activity index (r = 0.632, p = 0.015).Conclusion.Serum SDC-1 levels are increased in SLE patients with nephritis, indicating that SDC-1 might be a useful serum biomarker for active LN.


Lupus ◽  
2017 ◽  
Vol 26 (9) ◽  
pp. 959-966 ◽  
Author(s):  
S Shenavandeh ◽  
S Habibi

Introduction The clinical expression of systemic lupus erythematosus (SLE) is the consequence of endothelial cell damage leading to serious multiple organ dysfunction. The aim of this study was to assess the association between nailfold capillaroscopic changes and disease activity, skin and renal involvement in patients with SLE. Methods Demographic variables, clinical manifestations and laboratory data of 108 patients with SLE were investigated. Nailfold capillaroscopy (NFC) was performed in all patients. Result Morphological changes in NFC were observed in 102 out of 108 (94.4%) SLE patients. Minor changes were found in 33 (30.6%) and major changes in 69 (63.9%) cases. The disease activity was significantly higher in the patients with major changes ( p < 0.002). A higher incidence of microhaemorrhages was seen in patients with active SLE disease ( p < 0.04). In SLE patients with active skin involvement, the disturbed distribution ( p < 0.004) was more frequent and subtle changes ( p < 0.009) were less frequently observed as compared with patients without active skin involvement. In the group of SLE patients with renal involvement, no correlation was found between the capillary abnormalities and the presence of renal involvement ( p > 0.05), except for the elongated capillary loops, which were seen more often in patients with renal involvement than in patients without it ( p < 0.03). Conclusion The results of the study showed that capillary changes (abnormal capillaroscopy) were very common in patients with SLE, although there were no specific patterns like the ones in scleroderma patients, and some changes may be associated with disease activity, especially in patients with active skin involvement.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Jingjing Sun ◽  
Xue Li ◽  
Haotian Zhou ◽  
Xiaoyun Liu ◽  
Jingjing Jia ◽  
...  

Objective. Systemic lupus erythematosus (SLE) is an immune disease characterized by multiorgan involvement. Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most devastating complications of SLE, which lacks efficient diagnostic biomarkers. The recent studies on the anti-GAPDH autoantibodies suggested its potential pathogenic roles in NPSLE. However, the clinical relevance of the anti-GAPDH autoantibodies in patients with SLE is still elusive. In this study, we sought to determine the serum levels of the anti-GAPDH autoantibodies in patients with SLE to investigate the clinical significance of the anti-GAPDH autoantibodies in SLE. Methods. Concentrations of the glyceraldehyde 3-phosphate dehydrogenase autoantibodies (anti-GAPDH autoantibodies) in the serum of 130 SLE patients and 55 healthy individuals were determined by enzyme-linked immunosorbent assay (ELISA). Among the 130 SLE patients, 95 were SLE patients without neuropsychiatric symptoms and 35 had NPSLE. White blood cell (WBC) count, hemoglobin (HB), platelet count (PLT), IgG, IgA, IgM, anti-dsDNA, C3, C4, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), RF, anti-cardiolipin (Acl), ANA, AnuA, anti-SSA, anti-SSB, β2-GPI, urinalysis, and 24 h urine protein were measured by standard laboratory techniques. Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index scores were evaluated accordingly. Results. The serum levels of the anti-GAPDH autoantibodies were significantly elevated in the SLE patients, especially in the patients with NPSLE (P=0.0011). Elevated serum anti-GAPDH was correlated with increased SLEDAI-2K (P=0.017), ESR, IgG, and IgM and associated with increased intracranial pressure and incidence of cerebrovascular lesions, but it was protective for seizure disorder incidence. Conclusions. Serum anti-GAPDH autoantibody was increased in both groups of SLE patients with or without neuropsychiatric symptoms and associated with disease severity. It could become an indicator of tissue damages in the brain for the future clinical practice.


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