scholarly journals Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status

2021 ◽  
Vol 12 ◽  
Author(s):  
Shaomin Gong ◽  
Shi Jin ◽  
Yang Li ◽  
Wuhua Jiang ◽  
Zhen Zhang ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Macrophage Activation ◽  
Clinical Manifestations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Soluble Cd163 ◽  
Remission Status ◽  
Potential Biomarker ◽  
Noninvasive Biomarker ◽  
Monocytes And Macrophages ◽  
Noninvasive Biomarkers

Noninvasive biomarkers of disease activity are needed to predict disease remission status in patients with IgA nephropathy (IgAN). Soluble CD163 (sCD163), shed by monocytes and macrophages, is a potential biomarker in diseases associated with excessive macrophage activation. We investigated the association of urinary sCD163 (u-sCD163) with histopathological activity and clinical manifestations in 349 patients with biopsy-diagnosed IgAN. U-sCD163 was measured via enzyme-linked immunosorbent assay. In patients with IgAN, higher u-sCD163 levels were associated with histological lesions of greater severity, as well as more proteinuria and poorer renal function. Additionally, u-sCD163 was correlated with infiltration of tubulointerstitial CD163+ macrophages. High u-sCD163 levels (>3.57 ng/mg Cr) were associated with a 2.66-fold greater risk for IgAN remission failure in adjusted analyses. Adding u-sCD163 levels to the model containing clinical data at biopsy and MEST-C score significantly improved the risk prediction of IgAN remission status (AUC 0.788). Together, our results suggest that u-sCD163 may be a useful noninvasive biomarker to evaluate disease severity and remission status of IgAN.

Usefulness of soluble CD163 as a biomarker for macrophage activation syndrome associated with systemic lupus erythematosus

Lupus ◽  
2019 ◽  
Vol 28 (8) ◽  
pp. 986-994 ◽  
Author(s):  
A Nishino ◽  
Y Katsumata ◽  
H Kawasumi ◽  
S Hirahara ◽  
Y Kawaguchi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Serum Ferritin ◽  
Lupus Erythematosus ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Systemic Lupus ◽  
Soluble Cd163 ◽  
Activation Syndrome

ObjectiveWe aimed to study the usefulness of serum soluble CD163 (sCD163) as a biomarker for macrophage activation syndrome (MAS) associated with systemic lupus erythematosus (SLE).MethodsSerum sCD163 levels were retrospectively measured by enzyme-linked immunosorbent assay for SLE patients associated with MAS (SLE-MAS), lupus nephritis (LN), or autoimmune hemolytic anemia (AIHA) and/or immune thrombocytopenia (ITP) and healthy controls (HCs). Posttreatment samples were also evaluated in the available SLE-MAS patients. The associations between serum sCD163 levels and clinical information were statistically analyzed.ResultsThe serum sCD163 levels in SLE-MAS, LN and SLE-AIHA/ITP groups were significantly higher than those in HCs ( n = 17, 29, 13, and 68, respectively; p < 0.01 for all comparisons). In addition, the serum sCD163 levels in the SLE-MAS group were even higher than those in the LN and SLE-AIHA/ITP groups ( p < 0.01 for both comparisons). Serum sCD163 levels were correlated with the SLE Disease Activity Index 2000 scores ( r = 0.53), whereas they were not correlated with the serum ferritin levels. With the determined cut-off value, the sensitivity and specificity of serum sCD163 for the diagnosis of SLE-MAS were 59% and 86%, respectively. Retesting showed that the serum sCD163 levels decreased significantly following treatment in parallel with disease amelioration in the SLE-MAS group ( p < 0.01).ConclusionsThe present study suggests the usefulness of serum sCD163 as a diagnostic and disease-activity biomarker for SLE-associated MAS. Serum sCD163 might also have a different role as a biomarker for SLE-associated MAS than serum ferritin does.

scholarly journals The levels of urinary joining chain containing IgG immune complexes are associated with disease severity in IgA nephropathy

2019 ◽  
Author(s):  
Guanhong Li ◽  
Cai Yue ◽  
Xiaohong Fan ◽  
Yubing Wen ◽  
Gang Chen ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Iga Nephropathy ◽  
Disease Severity ◽  
Immune Complexes ◽  
Kidney Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Creatinine Ratio ◽  
Operating Characteristics ◽  
Potential Biomarker ◽  
Tubulointerstitial Lesions

Abstract Background: Circulating levels of aberrantly glycosylated IgA1 and its immune complexes (IgA/IgG-IC) are elevated and correlated with disease severity in IgA nephropathy (IgAN). The pathologic IgA containing immune complexes deposits in the kidney were found to be in dimeric or polymeric forms, suggesting that those deposited IgA immune complexes contain joining chain, which is critical for the multimerization and transportation of IgA. Both the dimeric IgA and polymeric IgA can cause renal damage by inducing the release of cytokines from mesangial cells. We aimed to investigate the urinary J chain containing IgG immune complexes/creatinine ratio (UJGCR) and analyze its relationship with disease severity in IgAN. Methods: The UJGCR were measured by sandwich enzyme linked immunosorbent assay in 26 patients with IgAN, 31 patients with other kidney diseases and 32 healthy volunteers. Results: The levels of UJGCR were higher in patients with IgAN than that in non-IgAN patients ( P =0.006) and healthy volunteers ( P <0.0001). Importantly, receiver operating characteristics curve analysis confirmed that UJGCR had good discrimination between non-IgAN patients and IgAN patients. The levels of UJGCR positively correlated with 24-hour urinary protein excretion (r=0.63, P =0.0006), serum creatinine (r=0.55, P =0.003), and negatively correlated with estimated glomerular filtration rate (r= -0.61, P =0.0008) in IgAN. Furthermore, the levels of UJGCR were higher in IgAN patients with IgA mesangial deposition of (+/++) than patients with (+++/++++). And IgAN patients with tubular atrophy/interstitial fibrosis showed higher levels of UJGCR than that without ( P =0.03). Similarly, the levels of urinary IgA-IgG/creatinine ratio (UAGCR) were also found to be elevated and associated with clinical and pathological parameters as UJGCR in IgAN. Besides, significant correlation between the levels of UJGCR and UAGCR was shown, suggesting UJGCR was mainly composed of J-IgA-IgG. Conclusions: The levels of UJGCR are associated with disease severity in IgAN. UJGCR is a potential biomarker for both glomerular and tubulointerstitial lesions in IgAN.

scholarly journals The levels of urinary joining chain containing IgG immune complexes are associated with disease severity in IgA nephropathy

2019 ◽  
Author(s):  
Guanhong Li ◽  
Cai Yue ◽  
Xiaohong Fan ◽  
Yubing Wen ◽  
Gang Chen ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Iga Nephropathy ◽  
Disease Severity ◽  
Immune Complexes ◽  
Kidney Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Creatinine Ratio ◽  
Operating Characteristics ◽  
Potential Biomarker ◽  
Tubulointerstitial Lesions

Abstract Background: Circulating levels of aberrantly glycosylated IgA1 and its immune complexes (IgA/IgG-IC) are elevated and correlated with disease severity in IgA nephropathy (IgAN). The pathologic IgA containing immune complexes deposits in the kidney were found to be in dimeric or polymeric forms, suggesting that those deposited IgA immune complexes contain joining chain, which is critical for the multimerization and transportation of IgA. Dimeric IgA and polymeric IgA both can cause renal damage by inducing release of cytokines from mesangial cells. We aimed to investigate the urinary J chain containing IgG immune complexes/creatinine ratio (UJGCR) and analyze its relationship with disease severity in IgAN. Methods: The UJGCR were measured by sandwich enzyme linked immunosorbent assay in 26 patients with IgAN, 31 patients with other kidney diseases and 32 healthy volunteers. Results: The levels of UJGCR were higher in patients with IgAN than that in non-IgAN patients ( P =0.006) and healthy volunteers ( P <0.0001). Importantly, receiver operating characteristics curve analysis confirmed that UJGCR had good discrimination between non-IgAN patients and IgAN patients. The levels of UJGCR positively correlated with 24-hour urinary protein excretion (r=0.63, P =0.0006), serum creatinine (r=0.55, P =0.003), and negatively correlated with estimated glomerular filtration rate (r= -0.61, P =0.0008) in IgAN. Furthermore, the levels of UJGCR were higher in IgAN patients with IgA mesangial deposition of (+/++) than patients with (+++/++++). And IgAN patients with tubular atrophy/interstitial fibrosis showed higher levels of UJGCR than that without ( P =0.03). Similarly, the levels of urinary IgA-IgG/creatinine ratio (UAGCR) were also found to be elevated and associated with clinical and pathological parameters as UJGCR in IgAN. Besides, significant correlations between the levels of UJGCR and UAGCR were shown, suggesting UJGCR were mainly composed of J-IgA-IgG. Conclusions: The levels of UJGCR are associated with disease severity in IgAN. UJGCR is a potential biomarker for both glomerular and tubulointerstitial lesions in IgAN.

scholarly journals The acute phase response protein SERPINA3 is increased in tear fluid from the unaffected eyes of patients with unilateral acute anterior uveitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jon Roger Eidet ◽  
Maja Akopian ◽  
Ole K. Olstad ◽  
Øystein Kalsnes Jørstad ◽  
Morten C. Moe ◽  
...  
Keyword(s):  
Acute Phase ◽  
Anterior Uveitis ◽  
Acute Phase Response ◽  
Phase Response ◽  
Tear Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Bacterial Keratitis ◽  
Acute Anterior Uveitis ◽  
Potential Biomarker

Abstract Background To identify candidate tear fluid biomarkers in patients with unilateral acute anterior uveitis (AAU) that can aid in the differentiation between these patients and patients with bacterial keratitis or healthy controls. Methods Thirteen patients (40.1 ± 16.2 years of age) with unilateral AAU, seven patients with unilateral bacterial keratitis (40.2 ± 15.3 years of age), and 14 healthy subjects (41.1 ± 11.6 years of age) were included. The tear proteome of affected eyes was compared with that of the unaffected eye or healthy controls. Proteins were identified by liquid chromatography tandem mass spectrometry and enzyme-linked immunosorbent assay. Results Relative protein ratios were detected and calculated for 272 unique proteins. Compared with healthy controls and the unaffected eye, the top upregulated proteins in AAU eyes were submaxillary gland androgen regulated protein 3B (SMR3B) and SMR3A. Similarly, the top upregulated proteins in bacterial keratitis were S100 calcium-binding protein A9 and orosomucoid 2. The acute phase response protein Serpin Family A Member 3 (SERPINA3) was increased in the healthy eye of AAU patients (P = 0.019) compared with healthy controls. Laser flare measurements in affected eyes of AAU patients showed positive logarithmic correlation with SERPINA3 in tear samples of the unaffected eye (P = 0.022). The use of SERPINA3 as a tear biomarker yielded a sensitivity of 85% and a specificity of 71% in detecting patients with AAU in the study population. Conclusions The acute phase response protein SERPINA3 was increased in tear samples of unaffected eyes of patients with unilateral AAU compared with healthy controls. This study highlights SERPINA3 as a potential biomarker for AAU. Future research should explore the dynamic properties of SERPINA3 in the tear fluid of active and quiescent uveitis eyes.

scholarly journals Circulating Natural IgM Antibodies against Angiogenin in the Peripheral Blood Sera of Patients with Osteosarcoma as Candidate Biomarkers and Reporters of Tumorigenesis

2010 ◽  
Vol 2 ◽  
pp. BIC.S6040 ◽  
Author(s):  
Yulia A. Savitskaya ◽  
Genaro Rico ◽  
Luis Linares ◽  
Roberto González ◽  
René Téllez ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Sensitivity And Specificity ◽  
Peripheral Blood ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Healthy Individuals ◽  
Igm Antibodies ◽  
Potential Biomarker ◽  
Increased Risk ◽  
Natural Igm

Background Tumor immunology research has led to the identification of a number of tumor-associated self antigens, suggesting that most tumors trigger an immunogenic response, as is the case in osteosarcoma, where the detection of natural serum IgM antibodies might achieve the diagnosis of osteosarcoma. Natural IgM antibodies to tumor-associated proteins may expand the number of available tumor biomarkers for osteosarcoma and may be used together in a serum profile to enhance test sensitivity and specificity. Natural IgM antibodies can be consistently detected in the peripheral blood sera months to years before the tumor is diagnosed clinically. The study of the level of a potential biomarker many months (or years) prior to diagnosis is fundamentally important. Integrated circulating and imaging markers in clinical practice treating osteosarcoma have potential applications for controlling tumor angiogenesis. Objectives To study the expression of natural IgM antibodies to the tumor antigens of angiogenesis in the peripheral blood sera of osteosarcoma patients and healthy individuals, and to develop serum-based predictive biomarkers. Methods Peripheral venous blood samples were collected from 117 osteosarcoma patients and 117 patients with other tumors. All diagnosis was histologically confirmed. Staging of patients was performed according to the Enneking Surgical Staging System. The control group consisted of 117 age- and sex- matched healthy individuals. In this study, novel immunoconjugates were designed, synthesized and then used to develop a rapid, specific and sensitive enzyme-linked immunosorbent assay (ELISA) method to detect angiogenin (ANG)–IgM directly in the peripheral blood sera of humans. Results Serum ANG–IgM levels are significantly higher in osteosarcoma patients than in healthy individuals ( P < 0.005). Serum ANG–IgM levels varied widely, but were highly dependent on the concentration of IgM (r = 0.85; P < 0.0005). We found ANG–IgM in the sera of 85% of newly diagnosed osteosarcoma patients and ANG–IgM levels were significantly higher in osteosarcoma patients compared to any other tumors ( P < 0.001). Conclusions These results demonstrated that the combined biomarker ANG–IgM has greater sensitivity and specificity in early diagnosis of osteosarcoma patients than the traditional biomarkers (ANG and vascular endothelial growth factor). Circulating ANG–IgM immune complexes can potentially serve as a biomarker for increased risk of osteosarcoma, because relatively high serum levels were also detected in otherwise healthy individuals with a first degree family history of osteosarcoma and in patients with a diagnosis of benign conditions. Immunological aspects of angiogenesis for managing osteosarcoma will have a practical value in early diagnosis, prognosis and monitoring response to antiangiogenic therapy.

scholarly journals Circulating Heme Oxygenase-1: Not a Predictor of Preeclampsia but Highly Expressed in Pregnant Women Who Subsequently Develop Severe Preeclampsia

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Valéria C. Sandrim ◽  
Mayara Caldeira-Dias ◽  
Heloisa Bettiol ◽  
Marco Antonio Barbieri ◽  
Viviane Cunha Cardoso ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Heme Oxygenase ◽  
Clinical Symptoms ◽  
Severe Preeclampsia ◽  
Urine Samples ◽  
University Hospital ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heme Oxygenase 1 ◽  
Study Cohort ◽  
Potential Biomarker

Preeclampsia is the major cause of maternal and fetal deaths worldwide. Circulating biomarker concentrations to predict preeclampsia must be determined. Therefore, the objective was to evaluate heme oxygenase-1 (HO-1) concentration in both plasma and urine samples from pregnant women before the development of preeclampsia and to identify a potential biomarker for preeclampsia development. We performed a case-control study nested in a prospective study cohort at University Hospital of the Ribeirao Preto Medical School, University of São Paulo (HCFMRP-USP), Ribeirao Preto, Brazil. Of 1400 pregnant women evaluated at 20–25 weeks of gestation, 460 delivered in hospitals outside our institution. Of 940 pregnant women who completed the protocol, 30 developed preeclampsia (cases, 14 cases of severe preeclampsia and 16 cases of mild preeclampsia). Healthy pregnant women (controls, n=90) were randomly selected from the remaining 910 participants. HO-1 concentration was evaluated in plasma/urine samples by using a commercial enzyme-linked immunosorbent assay kit. We found similar HO-1 levels in the plasma and urine for case and control groups. In the subgrouped preeclampsia, lower plasma HO-1 levels were found in mild compared with severe preeclampsia. We conclude that plasma HO-1 levels were not altered at 20–25 weeks of gestation before the manifestation of preeclampsia symptoms. Pregnant women who subsequently develop severe preeclampsia show higher expression of HO-1. This may be indicative of important underlying pathophysiologic mechanisms that differentiate between mild and severe preeclampsia and may possibly be related to a higher prooxidative status even before the development of clinical symptoms.

scholarly journals Evaluation of Serum Apolipoprotein E as a Potential Biomarker for Pharmacological Therapeutic Efficacy Monitoring in Dopamine Dictated Disease Spectrum of Schizophrenia and Parkinson’s disease: A Preliminary Study

2018 ◽  
Vol 10 ◽  
pp. 117957351880358 ◽  
Author(s):  
Ashish Kumar Gupta ◽  
Komal Rani ◽  
Surabhi Swarnkar ◽  
Gaurav Khunger Kumar ◽  
Mohd Imran Khan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Apolipoprotein E ◽  
Pharmacological Intervention ◽  
Enzyme Linked Immunosorbent Assay ◽  
Disease States ◽  
Disease Spectrum ◽  
Potential Biomarker ◽  
Schizophrenic Patients ◽  
The Right

Aim of the Study: Parkinson’s disease and schizophrenia are disease end points of dopaminergic deficit and hyperactivity, respectively, in the mid brain. Accordingly, current medications aim to restore normal dopamine levels, overshooting of which results in adverse effects of psychosis and extra-pyramidal symptoms, respectively. There are currently no available laboratory tests to guide treatment decisions or help predict adverse side effects of the drugs. The aim was to therefore explore the possibility of using apolipoprotein E as a biomarker to monitor pharmacological intervention in dopamine dictated states of Parkinson’s disease and schizophrenia for optimum therapy. Methods: Naïve and treated, Parkinson’s disease and schizophrenic patients were recruited from neurology and psychiatry clinics. Serum of healthy volunteers was collected as controls. Serum concentrations of apolipoprotein E was estimated by enzyme-linked immunosorbent assay (ELISA). Pathway analysis was carried out to delineate the interactions of apolipoprotein E in Parkinson’s disease and schizophrenia. Results: Apolipoprotein E levels are higher in Parkinson’s disease patients as compared with schizophrenic samples ( P < .05). Also, post-treatment apolipoprotein E levels in both disease states were at par with levels seen in healthy controls. The interactions of apolipoprotein E validate the results and place the differential expression of the protein in Parkinson’s disease and schizophrenia in the right perspective. Conclusion: Apolipoprotein E concentration across the dopaminergic spectrum suggests that it can be pursued not only as a potential biomarker in schizophrenia and Parkinson’s disease, but can also be an effective tool for clinicians to determine efficacy of drug-based therapy.

scholarly journals Plasma Fibulin-3 as a Potential Biomarker for Patients with Asbestos-Related Diseases in the Han Population

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Zhaoqiang Jiang ◽  
Shibo Ying ◽  
Wei Shen ◽  
Xianglei He ◽  
Junqiang Chen ◽  
...  
Keyword(s):  
Operating Characteristic ◽  
Asbestos Exposure ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Early Screening ◽  
Receiver Operating Characteristic Curves ◽  
Chinese Populations ◽  
Pleural Plaques ◽  
Potential Biomarker ◽  
Group A

Fibulin-3 has been reported as a potential biomarker for mesothelioma. However, little is known about the diagnostic efficacies of fibulin-3 for asbestos-related diseases (ARDs) in China. This study was to investigate the utility of fibulin-3 for asbestos exposure and ARDs. A total of 430 subjects were recruited from Southeast China, including healthy individuals, asbestos-exposed (AE) individuals, and patients with pleural plaques (PP), asbestosis, and malignant pleural mesothelioma (MPM). Plasma fibulin-3 was measured using the enzyme-linked immunosorbent assay. Linear regression analyses were applied to explore the influencing factors of fibulin-3. Receiver operating characteristic curves were used to determine the cutoff values. The median fibulin-3 level of subjects in the mesothelioma group was higher than that in other groups. Subjects in the asbestosis group had higher median fibulin-3 level than those in the control group. A higher fibulin-3 level was found in the group with ≥10 years of asbestos exposure as compared with control groups. The AUCs of fibulin-3 for distinguishing MPM subjects from control, AE, PP, and asbestosis subjects were 0.92, 0.88, 0.90, and 0.81, respectively. Our study provided evidence that fibulin-3 could be a potential biomarker for the early screening of MPM, but not of other nonmalignant ARDs in Chinese populations.

scholarly journals ABD-Derived Protein Blockers of Human IL-17 Receptor A as Non-IgG Alternatives for Modulation of IL-17-Dependent Pro-Inflammatory Axis

2018 ◽  
Vol 19 (10) ◽  
pp. 3089 ◽  
Author(s):  
Marie Hlavničková ◽  
Milan Kuchař ◽  
Radim Osička ◽  
Lucie Vaňková ◽  
Hana Petroková ◽  
...  
Keyword(s):  
Cell Surface ◽  
Clinical Manifestations ◽  
Cell Surface Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interleukin 17 ◽  
Normal Human Skin ◽  
High Affinity ◽  
Th 17 ◽  
Surface Receptor

Interleukin 17 (IL-17) and its cognate receptor A (IL-17RA) play a crucial role in Th17 cells-mediated pro-inflammatory pathway and pathogenesis of several autoimmune disorders including psoriasis. IL-17 is mainly produced by activated Th-17 helper cells upon stimulation by IL-23 and, via binding to its receptors, mediates IL-17-driven cell signaling in keratinocytes. Hyper-proliferation of keratinocytes belongs to major clinical manifestations in psoriasis. To modulate IL-17-mediated inflammatory cascade, we generated a unique collection of IL-17RA-targeting protein binders that prevent from binding of human IL-17A cytokine to its cell-surface receptor. To this goal, we used a highly complex combinatorial library derived from scaffold of albumin-binding domain (ABD) of streptococcal protein G, and ribosome display selection, to yield a collection of ABD-derived high-affinity ligands of human IL-17RA, called ARS binders. From 67 analyzed ABD variants, 7 different sequence families were identified. Representatives of these groups competed with human IL-17A for binding to recombinant IL-17RA receptor as well as to IL-17RA-Immunoglobulin G chimera, as tested in enzyme-linked immunosorbent assay (ELISA). Five ARS variants bound to IL-17RA-expressing THP-1 cells and blocked binding of human IL-17 cytokine to the cell surface, as tested by flow cytometry. Three variants exhibited high-affinity binding with a nanomolar Kd value to human keratinocyte HaCaT cells, as measured using Ligand Tracer Green Line. Upon IL-17-stimulated activation, ARS variants inhibited secretion of Gro-α (CXCL1) by normal human skin fibroblasts in vitro. Thus, we identified a novel class of inhibitory ligands that might serve as immunosuppressive IL-17RA-targeted non-IgG protein antagonists.

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