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 ◽  
...  

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.

2019 ◽  
Author(s):  
Guanhong Li ◽  
Cai Yue ◽  
Xiaohong Fan ◽  
Yubing Wen ◽  
Gang Chen ◽  
...  

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.


2021 ◽  
Author(s):  
Ling-Yu Chu ◽  
Jian-Yuan Zhou ◽  
Yi-Xuan Zhao ◽  
Yan-Ting Ou ◽  
Tian Yang ◽  
...  

Background:Esophagogastric junction tumor (EGJ) is a rare but fatal disease with a rapid rising incidence worldwide in the late 20 years, and it lacks a convenient and safe method for diagnosis. This study aimed to evaluate the potential of serum CYR61 as a biomarker for the diagnosis of EGJ tumor. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to estimate CYR61 levels in sera of 152 EGJ tumor patients and 137 normal controls. Receiver operating characteristics (ROC) was carried out to evaluate the diagnostic accuracy. The Mann–Whitney’s U test was used to compare the difference of serum levels of CYR61 between groups. And chi-square tests were employed to estimate the correlation of the positive rate of serum CYR61 between/among subgroups. Results: Serum CYR61 levels were statistically lower in EGJ tumor and early-stage EGJ tumor patients than those in normal controls (P&lt;0.0001). The sensitivity, specificity, and the area under the curve (AUC) of this biomarker in EGJ tumor were 88.2%, 43.8% and 0.691, respectively, and those for early stage of EGJ tumor were 80.0%, 66.4% and 0.722, respectively. Analyses showed that there was no correlation between the clinical data and the levels of CYR61 (P&gt;0.05). Conclusion: This study showed that CYR61 might be a potential biomarker to assist the diagnosis of EGJ tumor.


Lupus ◽  
1993 ◽  
Vol 2 (1_suppl) ◽  
pp. 261-268 ◽  
Author(s):  
Tatsuo Yamamoto ◽  
Mitsumasa Nagase ◽  
Akira Hishida ◽  
Nishio Honda

The significance of interstitial inflammatory and chronic tubulointerstitial lesions was studied in relation to the severity of glomerular lesions in 62 patients with lupus nephritis and 88 with IgA nephropathy. Severe interstitial inflammatory and chronic tubulointerstitial lesions were found in patients with severe glomerular lesions in both lupus nephritis and IgA nephropathy. In such cases, the serum creatinine levels at biopsy were high and the renal prognosis was poor regardless of the underlying disease (lupus nephritis or IgA nephropathy). No IgA nephropathy patients with nil or mild glomerular lesions had moderate or severe interstitial inflammatory and/or chronic tubulointerstitial lesions. In contrast, predominantly severe interstitial inflammatory lesions were found in 36% of lupus nephritis patients with nil or mild glomerular lesions. The prevalence of interstitial immune complexes deposition was markedly high in those with predominant interstitial inflammatory lesions. However, the severity of chronic tubulointerstitial lesions was mild and renal function did not deteriorate in the mean follow-up periods of 68.6 months. It is suggested that, besides the tubulointerstitial lesions attributable to the severe concomitant glomerular damage, the interstitial deposition of immune complexes per se plays a pathogenic role in the interstitial inflammatory lesions in lupus nephritis. Its prognostic significance, however, was considered to be minor.


Lupus ◽  
2011 ◽  
Vol 20 (13) ◽  
pp. 1404-1410 ◽  
Author(s):  
WT Hung ◽  
YM Chen ◽  
JL Lan ◽  
HH Chen ◽  
YH Chen ◽  
...  

The objective of this study is to evaluate the correlation between antinucleosome antibodies and renal pathological activity in patients with proliferative lupus nephritis (LN). We evaluated 36 patients with proliferative LN, 14 non-renal lupus patients and 10 healthy volunteers. Lupus activity was assessed using the British Isles Lupus Assessment Group 2004 (BILAG 2004) index, serum anti-double stranded DNA (anti-dsDNA) levels, serum complement levels and daily urinary protein levels. All 36 lupus nephritis patients received renal biopsy. Antinucleosome antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Our results showed that levels of serum antinucleosome antibodies were significantly higher in LN patients (median 90.35 units/ml, interquartile range [IQR] 37.38–135.23) than in non-renal SLE patients (median 5.45 units/ml, IQR 2.6–28.93, p <0.05) and in healthy volunteers (median 3.35 units/ml, IQR 2.95–5.23, p <0.001). Serum levels of antinucleosome antibodies were positively correlated with BILAG index (Spearman’s r = 0.645, p <0.001) and serum anti-dsDNA antibody levels ( rs = 0.644, p <0.01), while serum levels of antinucleosome antibodies were negatively correlated with serum levels of C3 ( rs = -0.400, p <0.01) and C4 ( rs = -0.300, p <0.05). Serum levels of antinucleosome antibodies were positively correlated with the histological activity index of LN ( rs = 0.368, p <0.05). However, there was no significant correlation between serum levels of antinucleosome antibodies and the histological chronicity index. In conclusion, the serum level of antinucleosome antibodies is a potential biomarker for early recognition of renal involvement and evaluation of disease activity in SLE. Our preliminary results suggested that serum levels of antinucleosome antibodies might be a potential biomarker in evaluating pathological activity of LN.


2020 ◽  
Author(s):  
Hongxiang Lu ◽  
Anqiang Zhang ◽  
Dalin Wen ◽  
Juan Du ◽  
Jianhui Sun ◽  
...  

Abstract BackgroudVanin-1 plays a pivotal role in oxidative stress and the inflammatory response. However, its relationship with traumatic sepsis remains unknown. The aim of our study was to evaluate whether plasma vanin-1 expression can be used to predict traumatic sepsis in an early time.MethodsIn this three-stage prospective cohort study, severe trauma patients admitted to two hospitals from January 2015 to October 2018 were enrolled. Clinical data during hospitalization and APACHE II score were collected. Plasma vanin-1 levels were measured by enzyme linked immunosorbent assay. The associations among variables and traumatic sepsis were identified by logistic regression model. The receiver-operating characteristic curve was analyzed to evaluate the diagnostic efficiency of the selected factors.ResultsA total of 426 trauma patients (22 patients in the discovery cohort, 283 patients in the internal test cohort, and 121 patients in the external validation cohort) and 16 healthy volunteers were enrolled. The plasma vanin-1 level of trauma patients was significantly higher than that of healthy volunteers (P < 0.05), and sepsis patients had higher plasma vanin-1 than non-sepsis patients in the discovery trauma cohort (P < 0.05). In the internal test cohort, plasma vanin-1 levels at day 1 after trauma were significantly associated with the incidence of sepsis (OR = 3.92, 95% CI = 2.68–5.72, P = 1.62⊆10− 12). As a predictive biomarker, vanin-1 obtained a better area under the curve (AUC) (0.82, 95% CI = 0.77–0.87) than C-reaction protein (CRP) (0.62, 95% CI = 0.56–0.68, P < 0.0001), procalciton in (PCT) (0.66, 95% CI = 0.60–0.71, P < 0.0001), and Acute Physiology and Chronic Health Evaluation II (APACHE II) (0.71, 95% CI = 0.65–0.76, P = 6.70⊆10− 3). In addition, the clinical relevance between plasma vanin-1 and traumatic sepsis was validated in the external validation cohort (OR = 4.26, 95% CI = 2.22–8.17, P = 1.28⊆10− 5). The AUC of vanin-1 was 0.83 (95% CI = 0.75–0.89), which was better than that of CRP, PCT, and APACHE II.ConclusionsOur study demonstrated that plasma vanin-1 increased among trauma patients and was independently associated with the risk of sepsis. Vanin-1 might be a potential biomarker for the early prediction of traumatic sepsis.Trial registrationClinicaltrials.gov Identifier NCT01713205. Registered 24 October 2012.


2018 ◽  
Vol 32 (5) ◽  
pp. 380-387 ◽  
Author(s):  
Abigail Pulsipher ◽  
Brock M. Davis ◽  
Kristine A. Smith ◽  
Shaelene Ashby ◽  
Xuan Qin ◽  
...  

Background Calgranulin C (S100A12) is an innate immune peptide at the air–mucosal interface associated with neutrophil involvement, which when overexpressed has been implicated as a biomarker of inflammatory diseases. Decreased epithelial expression of certain innate immune peptides has been reported in chronic rhinosinusitis (CRS). We hypothesized that S100A12 is differentially expressed in the sinonasal mucosa of patients with CRS compared to controls and that S100A12 is a potential biomarker of CRS-specific quality of life (QOL) and disease severity. Methods A prospective observational study was conducted which included 70 patients: 17 controls, 28 having CRS without (CRSsNP), and 25 with (CRSwNP) nasal polyps. The expression of S100A12 and human neutrophil elastase (HNE) was assessed in the anterior ethmoid tissues from all patients using enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) analyses. Disease-specific QOL (Rhinosinusitis Disability Index) and disease severity (computed tomography [CT] and endoscopy) were evaluated and correlated to the expression levels of S100A12. Results S100A12 and HNE were significantly elevated in patients with CRSsNP compared to normal controls ( P < .05 and P < .001, respectively) and patients with CRSwNP ( P < .05 and P < .001, respectively), as measured by ELISA and IHC analyses. Patients with CRS exhibited worse CRS-specific disease severity compared to normal controls ( P < .05), and the increased protein levels of S100A12 were significantly correlated to disease severity, represented by CT scores ( P < .05). Conclusions S100A12 is differentially expressed in CRS subtypes and is significantly elevated in patients with CRSsNP and associated with CRS-specific disease severity.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shaomin Gong ◽  
Shi Jin ◽  
Yang Li ◽  
Wuhua Jiang ◽  
Zhen Zhang ◽  
...  

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 (&gt;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.


2020 ◽  
Author(s):  
Xingxing Yu ◽  
Yu Pan ◽  
Qinglin Fei ◽  
Xianchao Lin ◽  
Zhijiang Chen ◽  
...  

Abstract Background: Most of acute pancreatitis (AP) are mild and self-limiting, however, 15%-20% of patients develop severe AP (SAP) or moderately SAP (MSAP) with local or systemic complications. Infection complications (ICs) result in 40-70% morbidity and high mortality rates among SAP and MSAP patients. It’s require that early identification of SAP and MSAP patients at risk of developing ICs. Several studies have indicated that serum soluble programmed cell death protein (sPD-1) or programmed cell death 1 ligand (sPD-L1) levels were higher in patients with severe sepsis than in healthy volunteers, and have a predictive capacity for mortality. However, the role of serum soluble PD-1/PD-L1 in AP remains unclear. This study aimed to investigate whether the ICs of AP patients is associated with their sPD-1 and sPD-L1 levels, which were determined via enzyme-linked immunosorbent assay of peripheral blood samples from 63 MSAP and SAP patients and 30 healthy volunteers.Results: The serum sPD-1 levels in AP patients on days 1, 3 and 10 after onset were significantly increased in a time-dependent manner compared with that in healthy volunteers. Moreover, the AP patients with ICs had significantly higher serum sPD-1 levels than the AP patients without ICs. While serum sPD-L1 levels in AP patients were similar to that in healthy volunteers. Besides, serum levels of sPD-1/sPD-L1 10 were negatively correlated with circulating lymphocytes. Univariate and Multivariate regression analyses showed that the up-regulated serum sPD-1 level was an independent risk factor for ICs in AP. The area under the receiver operating characteristics (ROCs) curve indicated that combination with Acute Physiology and Chronic Health Evaluation II (APACHE II) score and serum sPD-1 level had a high accuracy in predicting ICs in AP patients.Conclusion: Serum sPD-1/sPD-L1 may be involved in the immunosuppressive process in AP. Moreover, the serum sPD-1 level may be an independent risk factor for predicting ICs in AP patients.


2015 ◽  
Vol 17 (2) ◽  
pp. S33
Author(s):  
R. Bu ◽  
G.Y. Cai ◽  
Q. Zhang ◽  
S. Liang ◽  
Y. Lu ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Michael Eisenhut ◽  
Dougal S. Hargreaves ◽  
Anne Scott ◽  
David Housley ◽  
Andrew Walters ◽  
...  

Background. Biomarkers to distinguish latent from active Mycobacterium (M.) tuberculosis infection in clinical practice are lacking. The urinary neopterin/creatinine ratio can quantify the systemic interferon-gamma effect in patients with M. tuberculosis infection. Methods. In a prospective observational study, urinary neopterin levels were measured by enzyme linked immunosorbent assay in patients with active tuberculosis, in people with latent M. tuberculosis infection, and in healthy controls and the urinary neopterin/creatinine ratio was calculated. Results. We included a total of 44 patients with M. tuberculosis infection and nine controls. 12 patients had active tuberculosis (8 of them culture-confirmed). The median age was 15 years (range 4.5 to 49). Median urinary neopterin/creatinine ratio in patients with active tuberculosis was 374.1 micromol/mol (129.0 to 1072.3), in patients with latent M. tuberculosis infection it was 142.1 (28.0 to 384.1), and in controls it was 146.0 (40.3 to 200.0), with significantly higher levels in patients with active tuberculosis (p<0.01). The receiver operating characteristics curve had an area under the curve of 0.84 (95% CI 0.70 to 0.97) (p<0.01). Conclusions. Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent infection and may be a significant predictor of active tuberculosis in patients with M. tuberculosis infection.


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