scholarly journals Anti-GAPDH Autoantibody Is Associated with Increased Disease Activity and Intracranial Pressure in Systemic Lupus Erythematosus

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.

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.


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.


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.


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.


Lupus ◽  
2016 ◽  
Vol 26 (2) ◽  
pp. 139-149 ◽  
Author(s):  
H Tydén ◽  
C Lood ◽  
B Gullstrand ◽  
A Jönsen ◽  
F Ivars ◽  
...  

Objectives Systemic lupus erythematosus (SLE) is associated with elevated levels of S100A8/A9, pro-inflammatory proteins mainly secreted by activated polymorphonuclear neutrophils (PMNs). The underlying mechanisms for increased S100A8/A9 levels and their relation to the clinical phenotype have not been carefully investigated. We assessed S100A8/A9 and S100A12 levels in SLE patient sera in relation to disease activity, clinical phenotype, presence of anti-dsDNA antibodies and ability to promote phagocytosis of necrotic cells (NCs) by PMNs. Methods Serum levels of S100A8/A9 and S100A12 were measured by ELISA in paired samples of 100 SLE patients at time points of higher and lower disease activity. Serum-mediated phagocytosis of NCs by PMNs was analysed by flow cytometry. Clinical data were recorded at time points of blood sampling. Results Serum levels of S100A8/A9 and S100A12 were increased in SLE patients with high disease activity compared to paired samples at low disease activity ( p = 0.01 and p = 0.008, respectively). Elevated levels of S100A8/A9 were particularly seen in patients with anti-dsDNA antibodies ( p = 0.01) and glomerulonephritis before treatment ( p = 0.02). Immunosuppressive therapy was associated with a reduction of S100A8/A9 serum levels ( p = 0.002). The ability of serum to support phagocytosis of NCs by PMNs was related to increased S100A8/A9 levels ( p = 0.01). Conclusions Elevated serum levels of S100A8/A9 may be used to monitor disease activity and response to treatment in SLE patients, especially in patients with glomerulonephritis. S100A12 may be a marker of disease activity in SLE. Increased S100A8/A9 levels may reflect immune-pathological processes involving phagocytosis of immune complexes by PMNs.


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 2020 ◽  
pp. 1-10
Author(s):  
Zhuochao Zhou ◽  
Aining Xu ◽  
Jialin Teng ◽  
Fan Wang ◽  
Yun Tan ◽  
...  

Background. Systemic lupus erythematosus (SLE) is a disease characterized by the production of a large number of autoantibodies. Defected phagocytosis of macrophage plays an important role in innate immunity in the pathogenesis of SLE. Tyro3 is a receptor responsible for the recognition of apoptotic cells during efferocytosis by macrophages. To investigate the role of Tyro3 receptor in macrophages’ efferocytosis of apoptotic cells in SLE, we aimed to reveal the clinical relevance and impact of Tyro3 autoantibody on SLE. Methods. The serum levels of IgG-type autoantibody against Tyro3 receptor were detected in new-onset, treatment-naïve SLE patients ( n = 70 ), rheumatoid arthritis (RA) ( n = 24 ), primary Sjögren’s Syndrome (pSS) ( n = 21 ), and healthy controls (HCs) ( n = 70 ) using enzyme-linked immunosorbent assay (ELISA). 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 RA, pSS, and HCs (all p < 0.0001 ). The levels of anti-Tyro3 IgG were positively associated with the SLE disease activity index (SLEDAI) score ( r = 0.254 , p = 0.034 ), erythrocyte sedimentation rate (ESR) ( r = 0.430 , p < 0.001 ), C-reactive protein (CRP) ( r = 0.246 , p = 0.049 ), and immunoglobulin G (IgG) ( r = 0.408 , p = 0.001 ) and negatively associated with haemoglobin (Hb) ( r = − 0.294 , p = 0.014 ). ROC curves illustrated that the anti-Tyro3 antibody could differentiate patients with SLE from HCs. Furthermore, flow cytometry and immunofluorescence demonstrated that purified anti-Tyro3 IgG inhibited the efferocytosis of macrophages ( p = 0.004 and 0.044, respectively) compared with unconjugated human IgG. Conclusions. These observations indicated that autoantibody against Tyro3 was associated with disease activity and could impair efferocytosis of macrophages. It might be a potential novel disease biomarker and might be involved in the pathogenesis of SLE.


Lupus ◽  
2021 ◽  
pp. 096120332110050
Author(s):  
Rory C Monahan ◽  
Liesbeth JJ Beaart-van de Voorde ◽  
Jeroen Eikenboom ◽  
Rolf Fronczek ◽  
Margreet Kloppenburg ◽  
...  

Introduction We aimed to investigate risk factors for fatigue in patients with systemic lupus erythematosus (SLE) and neuropsychiatric symptoms in order to identify potential interventional strategies. Methods Patients visiting the neuropsychiatric SLE (NPSLE) clinic of the Leiden University Medical Center between 2007–2019 were included. In a multidisciplinary consensus meeting, SLE patients were classified as having neuropsychiatric symptoms of inflammatory origin (inflammatory phenotype) or other origin (non-inflammatory phenotype). Fatigue was assessed with the SF-36 vitality domain (VT) since 2007 and the multidimensional fatigue inventory (MFI) and visual analogue scale (VAS) since 2011. Patients with a score on the SF-36 VT ≥1 standard deviation (SD) away from the mean of age-related controls of the general population were classified as fatigued; patients ≥2 SD away were classified as extremely fatigued. Disease activity was measured using the SLE disease activity index-2000. The influence of the presence of an inflammatory phenotype, disease activity and symptoms of depression and anxiety as measured by the hospital anxiety and depression scale (HADS) was analyzed using multiple regression analyses corrected for age, sex and education. Results 348 out of 371 eligible patients filled in questionnaires and were included in this study . The majority was female (87%) and the mean age was 43 ± 14 years. 72 patients (21%) had neuropsychiatric symptoms of an inflammatory origin. Fatigue was present in 78% of all patients and extreme fatigue was present in 50% of patients with an inflammatory phenotype vs 46% in the non-inflammatory phenotype. Fatigue was similar in patients with an inflammatory phenotype compared to patients with a non-inflammatory phenotype on the SF-36 VT (β: 0.8 (95% CI −4.8; 6.1) and there was less fatigue in patients with an inflammatory phenotype on the MFI and VAS (β: −3.7 (95% CI: −6.9; −0.5) and β: −1.0 (95% CI −1.6; −0.3)). There was no association between disease activity and fatigue, but symptoms of anxiety and depression (HADS) associated strongly with all fatigue measurements. Conclusion This study suggests that intervention strategies to target fatigue in (NP)SLE patients may need to focus on symptoms of anxiety and depression rather than immunosuppressive treatment.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danielle Perez-Bercoff ◽  
Hélène Laude ◽  
Morgane Lemaire ◽  
Oliver Hunewald ◽  
Valérie Thiers ◽  
...  

AbstractAPOBEC3 (A3) enzymes are best known for their role as antiviral restriction factors and as mutagens in cancer. Although four of them, A3A, A3B, A3F and A3G, are induced by type-1-interferon (IFN-I), their role in inflammatory conditions is unknown. We thus investigated the expression of A3, and particularly A3A and A3B because of their ability to edit cellular DNA, in Systemic Lupus Erythematosus (SLE), a chronic inflammatory disease characterized by high IFN-α serum levels. In a cohort of 57 SLE patients, A3A and A3B, but also A3C and A3G, were upregulated ~ 10 to 15-fold (> 1000-fold for A3B) compared to healthy controls, particularly in patients with flares and elevated serum IFN-α levels. Hydroxychloroquine, corticosteroids and immunosuppressive treatment did not reverse A3 levels. The A3AΔ3B polymorphism, which potentiates A3A, was detected in 14.9% of patients and in 10% of controls, and was associated with higher A3A mRNA expression. A3A and A3B mRNA levels, but not A3C or A3G, were correlated positively with dsDNA breaks and negatively with lymphopenia. Exposure of SLE PBMCs to IFN-α in culture induced massive and sustained A3A levels by 4 h and led to massive cell death. Furthermore, the rs2853669 A > G polymorphism in the telomerase reverse transcriptase (TERT) promoter, which disrupts an Ets-TCF-binding site and influences certain cancers, was highly prevalent in SLE patients, possibly contributing to lymphopenia. Taken together, these findings suggest that high baseline A3A and A3B levels may contribute to cell frailty, lymphopenia and to the generation of neoantigens in SLE patients. Targeting A3 expression could be a strategy to reverse cell death and the generation of neoantigens.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Conti Fabrizio ◽  
Ceccarelli Fulvia ◽  
Perricone Carlo ◽  
Massaro Laura ◽  
Marocchi Elisa ◽  
...  

Objectives. The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70–98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status.Methods. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA − (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM).Results. We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA −: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA − (21.1% and 18.7%, resp.;P=0.001). Serositis resulted significantly more frequent in anti-dsDNA − (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.;P<0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA − (21.8%,P=0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P=0.7).Conclusion. Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.


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