Clinical impact of urinary CD11b and CD163 on the renal outcomes of anti-neutrophil cytoplasmic antibody-associated glomerulonephritis

2020 ◽  
Author(s):  
Yuki Yokoe ◽  
Naotake Tsuboi ◽  
Takahiro Imaizumi ◽  
Akimitsu Kitagawa ◽  
Munetoshi Karasawa ◽  
...  
Keyword(s):  
Scavenger Receptor ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Enzyme Linked Immunosorbent Assay ◽  
Clinical Value ◽  
Crescent Formation ◽  
Immunoglobulin G4 ◽  
Α Subunit ◽  
Leukocyte Accumulation ◽  
Renal Histology ◽  
Cellular Crescent

Abstract Background The detection of leukocyte-derived CD11b (α subunit of integrin Mac-1) and CD163 (scavenger receptor) in urine may reflect renal inflammation in antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). The objective of this study was to evaluate the clinical significance of urinary CD11b (U-CD11b) and CD163 (U-CD163) in ANCA-GN. Methods U-CD11b and U-CD163 were examined using enzyme-linked immunosorbent assay in ANCA-GN urine samples from our institutional cohort (n = 88) and a nationwide cohort (n = 138), and their association with renal histology was subsequently analyzed. Logistic regression analyses were performed on a nationwide ANCA cohort to determine the associations of the two urinary molecules with renal remission failure at 6 months or with yearly estimated glomerular filtration rate (eGFR) slope over a 24-month observation period. Results U-CD11b and U-CD163 were significantly associated with cellular crescent formation and leukocyte accumulation in glomerular crescents. With regard to interstitial inflammation, both levels of U-CD11b and U-CD163 at diagnosis remarkably increased in ANCA-GN compared with the levels observed in nonglomerular kidney disorders including nephrosclerosis, immunoglobulin G4-related disease and tubulointerstitial nephritis; however, the presence of U-CD11b alone was significantly correlated with tubulointerstitial leukocyte infiltrates. Although neither U-CD11b nor U-CD163 at diagnosis was associated with remission failure at 6 months, multivariate analysis demonstrated that the baseline U-CD11b levels were significantly associated with the increase in eGFR following immunosuppressive therapy. Conclusions Although both U-CD11b and U-CD163 reflect renal leukocyte accumulation, U-CD11b at diagnosis provides additional clinical value by predicting the recovery rate after the treatment of ANCA-GN.

Identification of the hemoglobin scavenger receptor/CD163 as a natural soluble protein in plasma

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 378-380 ◽  
Author(s):  
Holger Jon Møller ◽  
Niels Anker Peterslund ◽  
Jonas Heilskov Graversen ◽  
Søren Kragh Moestrup
Keyword(s):  
Electrophoretic Mobility ◽  
Immunosorbent Assay ◽  
Broad Spectrum ◽  
Interleukin 6 ◽  
Soluble Protein ◽  
Healthy Subjects ◽  
Scavenger Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Myelomonocytic Leukemia ◽  
Healthy Persons

The hemoglobin scavenger receptor (HbSR/CD163) is an interleukin-6– and glucocorticoid-regulated macrophage/monocyte receptor for uptake of haptoglobin-hemoglobin complexes. Moreover, there are strong indications that HbSR serves an anti-inflammatory function. Immunoprecipitation and immunoblotting enabled identification of a soluble plasma form of HbSR (sHbSR) having an electrophoretic mobility equal to that of recombinant HbSR consisting of the extracellular domain (scavenger receptor cysteine-rich 1-9). A sandwich enzyme-linked immunosorbent assay was established and used to measure the sHbSR level in 130 healthy subjects (median, 1.87 mg/L; range, 0.73-4.69 mg/L). To evaluate the sHbSR levels in conditions with increased leukocyte stimulation and proliferation, 140 patients admitted to a hematological department were screened. Several patients, with a broad spectrum of diagnoses, had a level of sHbSR above the range of healthy persons. Patients with myelomonocytic leukemias and pneumonia/sepsis exhibited the highest levels (up to 67.3 mg/L). In conclusion, sHbSR is an abundant plasma protein potentially valuable in monitoring patients with infections and myelomonocytic leukemia.

scholarly journals Dynamic Analysis of Serum MMP-7 and Its Relationship with Disease Progression in Biliary Atresia: A Multicenter Prospective Study

2021 ◽  
Author(s):  
Shuiqing Chi ◽  
Peipei Xu ◽  
Pu Yu ◽  
Guoqing Cao ◽  
Haibin Wang ◽  
...  
Keyword(s):  
Prospective Study ◽  
Biliary Atresia ◽  
Disease Progression ◽  
Genetic Mutation ◽  
Mediation Effect ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Concentration ◽  
Clinical Value ◽  
Serum Samples ◽  
Matrix Metalloproteinase 7

Abstract PurposeWe aimed to assess the dynamic changing trend of serum matrix metalloproteinase-7 (MMP-7) in BA patients from diagnosis to LTx to further elucidate its clinical value in diagnosis and prognoses and its relationship with disease progression.MethodsIn this multicentre prospective study, a total of 440 cholestasis patients (direct bilirubin level of > 17 μmol/L) were enrolled. Serum and stool MMP-7 levels were measured using an enzyme-linked immunosorbent assay at different time points and analysed. The polymorphism of MMP-7 was assessed to explore the possible reasons for the low value in BA patients.Results:In neonate biliary atresia patients, using a cut-off value of > 26.73 ng/ml, serum MMP-7 had a AUC of 0.954. A genetic mutation (G137D) and rapid degradation of MMP-7 in serum samples could cause low MMP-7 levels in serum of BA patients. Four dynamic patterns of serum MMP-7 post-KPE were associated with prognosis. A high concentration of MMP-7 in the stool is linked to a decreased serum MMP-7 concentration. MMP-7 showed a mediation effect on the association between inflammation and liver fibrosis in BA patients. Serum MMP-7 was the only significant predictor at six weeks post-KPE and the most accurate predictor at three months post-KPE of survival with the native liver (SNL) in two years.Conclusion:As one of the critical factors associated with BA occurrence and progression, serum MMP-7 can be used for early diagnosis of BA and post-KPE MMP-7 level is the earliest prognostic biomarker so far.

scholarly journals Diagnostic Value of HSP90α and Related Markers in Lung Cancer

2021 ◽  
Author(s):  
zhimin yuan ◽  
longhao wang ◽  
songlin hong ◽  
lin li ◽  
ting tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Carcinoma ◽  
Diagnostic Value ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cancer Type ◽  
Clinical Value ◽  
Early Screening ◽  
Combined Application ◽  
Positive Rate ◽  
Diagnosis Of Lung Cancer

Abstract PurposeTo investigate the expression of heat shock protein 90α (HSP90α) in patients with lung cancer and the clinical value of HSP90α and other related markers in the diagnosis of lung cancer.MethodsThe plasma levels of HSP90α and related markers (CEA, NSE, CF211 and ProGRP) were detected in the blood of 560 patients with lung cancer by ELISA (enzyme-linked immunosorbent assay). Groups were divided according to the gender (male/female), age (age≤40, 41<age≤50, 51<age≤60, 61<age≤70 and age>70), types of lung cancer (small-cell, squamous carcinoma, adenocarcinoma, hybrid and other type), staging (Ⅰ, Ⅱ, Ⅲ and Ⅳ) and metastasis (metastasis and non-metastasis) separately. Wilcoxon Mann-Whitney test and Kruskal-Wallis test were used to compare statistical differences between two groups/among the multiple groups for each factor of HSP90α.ResultsNo statistical difference was found in plasma level of HSP90α among different age and gender groups (P> 0.05). In the group divided by lung cancer type, staging and metastasis status, there were statistical differences among different groups in HSP90α level (P< 0.05). R values of HSP90α correlated with other related markers in the diagnosis of lung cancer (P< 0.05). Although HSP90α and other related markers didn’t fit the satisfactory conformance, in terms of the positive rate of diagnosis, it was statistically differences in the diagnostic positive rate between HSP90α and each marker (P< 0.01). Reduced cut-off value of HSP90α in lung cancer can effectively improve the positive rate of diagnosis when combined with other tumor biomarkers.ConclusionsHSP90α has significant clinical value on early screening and diagnosis of lung cancer. The combined application of HSP90α and related markers can improve the positive rate of early diagnosis of lung cancer effectively.

scholarly journals P305 A location-based prediction model in Crohn’s disease regarding a novel serological marker, anti-Chitinase 3-like 1 autoantibodies

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S305-S306
Author(s):  
N Sipeki ◽  
P Kovats ◽  
C Deutschmann ◽  
P Schierack ◽  
D Roggenbuck ◽  
...  
Keyword(s):  
Immunoglobulin A ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Serological Marker ◽  
Secretory Iga ◽  
Mucosal Barrier ◽  
Enzyme Linked Immunosorbent Assay ◽  
Disease Course ◽  
Innate Immune Responses ◽  
Colonic Involvement ◽  
Underlying Mechanisms

Abstract Background A defective neutrophil regulation in IBD is thought to play an important role in the onset or manifestation of IBD, since it could lead to damage of the intestinal mucosal barrier by infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens. Like neutrophils in the context of innate immune responses, immunoglobulin A (IgA) as an acquired immune response partakes in the defence of the intestinal epithelium. Under normal conditions, IgA would contribute to the elimination of microbes, but in connection with the loss of tolerance to CHI3L1 in IBD, IgA could participate in the CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms. The tolerance brake to CHI3L1 and the occurrence of IgA auto-Abs to this particular target, the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear. Methods We aim to determine the predictive potential of immunoglobulin subtypes of a novel serological marker, anti-chitinase 3-like 1 autoantibodies (aCHI3L1) regarding determination of disease phenotype, therapeutic strategy and long-term disease course in a prospective referral adult IBD patient cohort. Immunoblotting of antineutrophil-cytoplasmic antibody-positive sera of IBD patients on neutrophil proteins and MALDI-TOF mass spectrometry were used to identify autoantigenic targets in IBD. Sera of 257 CD and 180 UC patients were assayed for IgG, IgA, and secretory IgA (sIgA) type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1 along with 86 healthy controls (HCONT). Results IgA type was more prevalent in CD than UC (29.2 vs. 11.1%) or HCONT (2.83%; p &lt; 0.0001 for both). However, sIgA subtype aCHI3L1 positivity was higher in both CD and UC compared with HCONT (39.3 and 32.8 vs. 4.65%, respectively; p &lt; 0.0001). The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement (p &lt; 0.0001 and p = 0.038, respectively) in CD. Complicated disease behaviour at sample procurement was associated with the presence of aCHI3L1 sIgA positivity (57.1% vs. 36.0%, p = 0.009). Whilst, IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in CD (46.9% vs. 25.7%, p = 0.005). In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of the diagnosis, positivity for IgA or sIgA type aCH3L1 predicted a faster progression towards complicated disease course in time-dependent models. This association disappeared after merging subgroups of different disease locations. Conclusion CHI3L1 is a novel neutrophil autoantigenic target in IBD. Consideration of antibody classes along with location-based prediction can revolutionise the future of serology in IBD.

scholarly journals The role of urinary renalase on early-stage renal damage in Chinese adults with primary hypertension

2020 ◽  
Vol 245 (6) ◽  
pp. 576-582
Author(s):  
Na-Na You ◽  
Wei-Hong Jiang ◽  
Ming-Yuan Lin ◽  
Xiao-Gang Li ◽  
Yu-Yan Wu ◽  
...  
Keyword(s):  
Kidney Function ◽  
Renal Injury ◽  
Renal Damage ◽  
Early Stage ◽  
Urinary Albumin ◽  
Primary Hypertension ◽  
Enzyme Linked Immunosorbent Assay ◽  
Creatinine Ratio ◽  
Clinical Value ◽  
Predictive Index

It would be of great clinical value to find an indicator that can accurately evaluate the early-stage renal injury in primary hypertension. Previous findings have shown renalase not only plays an important role in hypertension but also closely correlates with kidney function. The purpose of this study is to investigate whether urinary renalase could be used as a predictive index of early-stage renal damage in patients with primary hypertension. Urinary albumin to creatinine ratio (UACR) was used to divide subjects with primary hypertension into two groups: a no renal damage (NRD) group (UACR <30 mg/g) and an early-stage renal damage (RD) group (UACR >30 mg/g). Subjects with normal examination results were randomly included in a healthy control (HC) group. Urinary renalase was determined through an enzyme-linked immunosorbent assay (ELISA). Urinary renalase continued to reduce among the HC (n = 81), NRD (n = 84) and RD group (n = 80), while systolic blood pressure (SBP) increased. Urinary renalase was negatively correlated with SBP in all the groups. Among the subjects with stage 1 primary hypertension, urinary renalase in the RD group was lower than the NRD group, while the UACR was higher, and urinary renalase was negatively correlated with the UACR. A multiple linear stepwise regression analysis showed that there was a linear regression relationship between the increase of the UACR and urinary renalase, heart rate (HR), SBP and serum creatinine. In addition, the standardized partial regression coefficient of urinary renalase was the highest. The performance of urinary renalase as a marker for the diagnosis of early-stage renal damage in patients with primary hypertension was 0.968 with a cut off value of 2.01 µg/ml. Taken together, urinary renalase was further decreased in patients with early-stage renal damage and primary hypertension, and consequently, it could be used as a predictive index. Impact statement In patients with early-stage kidney damage of primary hypertension, there are no obvious structural or functional changes, which leads to a high level of diagnostic omissions. Therefore, it would be of great clinical value to find an indicator that can accurately evaluate the early-stage renal injury in primary hypertension. Urinary albumin to creatinine ratio (UACR) is a classic indicator used in early-stage renal damage, but it is affected by many factors. Renalase, a protein discovered by Xu in 2005, not only plays an important role in hypertension but also closely correlates with kidney function. In our study, we found that urinary renalase was further decreased in patients with early-stage renal damage in primary hypertension, and it could be used as a predictive index. This finding could help to diagnose the early-stage renal damage in primary hypertension much earlier and improve the prognosis of these patients.

Evaluation of immunoglobulin G4 subclass antibody in a peptide-based enzyme-linked immunosorbent assay for the serodiagnosis of human fascioliasis

Parasitology ◽  
2007 ◽  
Vol 134 (14) ◽  
pp. 2021-2026 ◽  
Author(s):  
C. TANTRAWATPAN ◽  
W. MALEEWONG ◽  
C. WONGKHAM ◽  
S. WONGKHAM ◽  
P. M. INTAPAN ◽  
...  
Keyword(s):  
Immunosorbent Assay ◽  
Large Scale ◽  
Laboratory Diagnosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Parasitic Infections ◽  
Immunoglobulin G4 ◽  
Predictive Values ◽  
Diagnostic Potential ◽  
Human Fascioliasis ◽  
Specific Igg4

SUMMARYTo improve the diagnosis of human fascioliasis caused byFasciola gigantica, we developed a peptide-based enzyme-linked immunosorbent assay (peptide-based ELISA) based on the detection of specific IgG4 subclass antibody. Two identified B-cell epitopes ofF. giganticacathepsin L1 were synthesized as single synthetic peptides, acetyl-DKIDWRESGYVTELKDQGNC-carboxamide (peptide L) and acetyl-DKIDWRESGYVTEVKDQGNC-carboxamide (peptide V), and their diagnostic potential was evaluated. The sera of 25 patients infected withF. gigantica, 212 patients with other parasitic infections, 32 cholangiocarcinoma patients and 57 healthy controls were analysed. The sensitivity, specificity, accuracy, and positive and negative predictive values of this assay were the same with both peptides at 100%, 99·7%, 99·7%, 96·2% and 100%, respectively. These highly sensitive and specific peptide-based ELISAs for the detection of specific IgG4 antibody could be useful for laboratory diagnosis of human fascioliasis in future large-scale surveys throughout Southeast Asia where this disease is prevalent.

The correlation of urinary podocytes and podocalyxin with histological features of lupus nephritis

Lupus ◽  
2017 ◽  
Vol 27 (3) ◽  
pp. 484-493 ◽  
Author(s):  
D Ikuma ◽  
K Hiromura ◽  
H Kajiyama ◽  
J Suwa ◽  
H Ikeuchi ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Sandwich Elisa ◽  
Characteristic Analysis ◽  
Crescent Formation ◽  
Class V ◽  
Histological Features ◽  
Cellular Crescent ◽  
Class Iv

Objectives The objective of this study was to test the correlation of urinary podocyte number (U-Pod) and urinary podocalyxin levels (U-PCX) with histology of lupus nephritis. Methods This was an observational, cross-sectional study. Sixty-four patients were enrolled: 40 with lupus nephritis and 24 without lupus nephritis (12 lupus nephritis patients in complete remission and 12 systemic lupus erythematosus patients without lupus nephritis). Urine samples were collected before initiating treatment. U-Pod was determined by counting podocalyxin-positive cells, and U-PCX was measured by sandwich ELISA, normalized to urinary creatinine levels (U-Pod/Cr, U-PCX/Cr). Results Lupus nephritis patients showed significantly higher U-Pod/Cr and U-PCX/Cr compared with patients without lupus nephritis. U-Pod/Cr was high in proliferative lupus nephritis (class III±V/IV±V), especially in pure class IV (4.57 (2.02–16.75)), but low in pure class V (0.30 (0.00–0.71)). U-Pod/Cr showed a positive correlation with activity index ( r=0.50, P=0.0012) and was independently associated with cellular crescent formation. In contrast, U-PCX/Cr was high in both proliferative and membranous lupus nephritis. Receiver operating characteristic analysis revealed significant correlation of U-Pod/Cr with pure class IV, class IV±V and cellular crescent formation, and the combined values of U-Pod/Cr and U-PCX/Cr were shown to be associated with pure class V. Conclusions U-Pod/Cr and U-PCX/Cr correlate with histological features of lupus nephritis.

scholarly journals Immunity to a Self-Derived, Channel-Forming Peptide in the Respiratory Tract

2007 ◽  
Vol 15 (2) ◽  
pp. 260-266 ◽  
Author(s):  
Frederik W. van Ginkel ◽  
Takeo Iwamoto ◽  
Bruce D. Schultz ◽  
John M. Tomich
Keyword(s):  
Amino Acid ◽  
Therapeutic Agent ◽  
Glycine Receptor ◽  
Delayed Type Hypersensitivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Α Subunit ◽  
Mucosal Adjuvant ◽  
Specific Immunity ◽  
Repeated Use ◽  
Specific Igg

ABSTRACT The channel-forming peptide NC-1130 was generated based on the amino acid sequence of the M2 segment of the spinal cord α-subunit of the glycine receptor and has been proposed as a therapeutic agent for anion channelopathies such as cystic fibrosis. Lysine adduction and amino acid substitutions at positions T19R and S22W of the peptide improved its performance as an ion channel. However, these modifications generated an altered self, potentially making this NC-1130 peptide immunogenic, which could preclude the repeated use of NC-1130 as a therapeutic agent. To measure the ability of NC-1130 to induce an immune response, it was administered nasally with or without cholera toxin (CT). The NC-1130 peptide, when given alone without adjuvant, induced very little peptide-specific immunity based on analyses of peptide-specific antibodies by enzyme-linked immunosorbent assay and enzyme-linked immunospot assay, induction of cytokine production, and delayed-type hypersensitivity (DTH) responses. The administration of NC-1130 with the mucosal adjuvant CT induced peptide-specific immunoglobulin G (IgG) antibodies and DTH responses and a Th2-dominant cytokine response. The coadministration of the strong mucosal adjuvant CT induced a systemic NC-1130-specific IgG response but not a mucosal peptide-specific antibody response. The lack of peptide-specific immunity and specifically mucosal immunity should allow repeated NC-1130 peptide applications to epithelial surfaces to correct anion channelopathies.

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