scholarly journals Serum Anti-14-3-3 Zeta Autoantibody as a Biomarker for Predicting Hepatocarcinogenesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ting Wang ◽  
Xue-ying Huang ◽  
Su-jun Zheng ◽  
Ye-ying Liu ◽  
Si-si Chen ◽  
...  
Keyword(s):  
Clinical Settings ◽  
Serum Samples ◽  
Novel Proteins ◽  
Human Sera ◽  
Early Hcc ◽  
Novel Biomarkers ◽  
Normal Human ◽  
Serial Serum ◽  
The Relationship

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Alpha-fetoprotein (AFP) is still the only serum biomarker widely used in clinical settings. However, approximately 40% of HCC patients exhibit normal AFP levels, including very early HCC and AFP-negative HCC; for these patients, serum AFP is not applicable as a biomarker of early detection. Thus, there is an urgent need to identify novel biomarkers for patients for whom disease cannot be diagnosed early. In this study, we screened and identified novel proteins in AFP-negative HCC and evaluated the feasibility of using autoantibodies to those protein to predict hepatocarcinogenesis. First, we screened and identified differentially expressed proteins between AFP-negative HCC tissue and adjacent non-tumor liver tissue using SWATH-MS proteome technology. In total, 2,506 proteins were identified with a global false discovery rate of 1%, of which 592 proteins were expressed differentially with 175 upregulated and 417 downregulated (adjusted p-value <0.05, fold-change FC ≥1.5 or ≤0.67) between the tumor and matched benign samples, including 14-3-3 zeta protein. For further serological verification, autoantibodies against 14-3-3 zeta in serum were evaluated using enzyme-linked immunosorbent, Western blotting, and indirect immunofluorescence assays. Five serial serum samples from one patient with AFP-negative HCC showed anti-14-3-3 zeta autoantibody in sera 9 months before the diagnosis of HCC, which gradually increased with an increase in the size of the nodule. Based on these findings, we detected the prevalence of serum anti-14-3-3 zeta autoantibody in liver cirrhosis (LC) patients, which is commonly considered a premalignant liver disease of HCC. We found that the prevalence of autoantibodies against 14-3-3 zeta protein was 16.1% (15/93) in LC patient sera, which was significantly higher than that in patients with chronic hepatitis (0/75, p = 0.000) and normal human sera (1/60, 1.7%, p = 0.01). Therefore, we suggest that anti-14-3-3 zeta autoantibody might be a biomarker for predicting hepatocarcinogenesis. Further follow-up and research of patients with positive autoantibodies will be continued to confirm the relationship between anti-14-3-3 zeta autoantibody and hepatocarcinogenesis.

Patient-Centered Empowerment Through Evidence-Based Engagement in Sensitive Clinical Settings

2020 ◽  
pp. 155-175
Author(s):  
Iris Reychav ◽  
Roger W. McHaney ◽  
Lin Zhu ◽  
Rami Moshonov
Keyword(s):  
Pap Test ◽  
Well Being ◽  
Clinical Settings ◽  
Evidence Based ◽  
Coding System ◽  
Educational Materials ◽  
Patient Centered ◽  
Shared Information ◽  
The Relationship

Patient-centered empowerment is enhanced through evidence-based engagement in stressful medical situations. The current study provided expert-vetted educational materials in dynamic text and video formats using the 5S approach. The materials are relevant, reliable, and readable for patients with abnormal Pap test results. Findings indicated patients that understood the information better were more engaged. Engagement was measured using a coding system that kept track of explicitly shared information, requested recommendations, and tacit knowledge during patient-physician interaction. Other outcomes were that dynamic text had a greater impact on engagement in both initial and follow-up meetings. Important findings included that those who found the dynamic text relevant had their social well-being, self-esteem, optimism, and acceptance improved in initial meetings. Those who found the dynamic text reliable were more confident in the relationship with their physician in follow-up meetings and felt their social well-being was improved in both initial and follow-up meetings.

scholarly journals Antibody response in patients with Gaucher disease after repeated infusion with macrophage-targeted glucocerebrosidase

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1402-1409 ◽  
Author(s):  
SM Richards ◽  
TA Olson ◽  
JM McPherson
Keyword(s):  
Gaucher Disease ◽  
Mean Value ◽  
Patient Treatment ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Enzyme Replacement ◽  
Human Sera ◽  
Normal Human ◽  
Igg1 Subclass

Abstract Recent clinical data have shown that enzyme replacement therapy with macrophage-targeted glucocerebrosidase (GCR) can be effective in treating type 1 Gaucher disease. Sera from 262 patients, repeatedly infused with GCR, were assessed for the presence of antibodies to this therapeutic protein. Patient serum samples obtained at 3-month intervals were assessed by enzyme-linked immunosorbent assay and those with values greater than two standard deviations above the mean value obtained with a pool of normal human sera were further characterized by radioimmunoprecipitation. At the time of these analyses, the duration of patient treatment varied from 3 months to approximately 3 years. Of the 262 patients analyzed, 34 (12.9%) showed IgG antibodies, as confirmed by radioimmunoprecipitation. All patients who seroconverted did so within 1 year of treatment. The predominant antibody developed was the IgG1 subclass. Fourteen patients in the study experienced periodic symptoms suggestive of immediate hypersensitivity. Nine of these 14 patients had antibody to GCR as determined by radioimmunoprecipitation, whereas 5 patients were antibody negative. There was no evidence of the development of IgE antibodies in these 14 patients. The presence of GCR antibodies did not appear to effect efficacy of therapy in any of the patients treated to date.

scholarly journals Effects of Pretreating Serum Samples on the Performance of a Latex Agglutination Test for Serodiagnosis of Paracoccidioidomycosis

2011 ◽  
Vol 19 (3) ◽  
pp. 386-390 ◽  
Author(s):  
Fabíola Silveira-Gomes ◽  
Silvia Helena Marques-da-Silva
Keyword(s):  
Sensitivity And Specificity ◽  
Bacterial Infections ◽  
Paracoccidioides Brasiliensis ◽  
Latex Agglutination ◽  
Agglutination Test ◽  
Latex Agglutination Test ◽  
Serum Samples ◽  
Content Type ◽  
Human Sera ◽  
Normal Human

ABSTRACTParacoccidioidomycosis (PCM) is a fungal disease caused byParacoccidioides brasiliensis, and Brazil is one of the principal countries where it is endemic. Diagnosis is based on the observation of buddingP. brasiliensisyeast in clinical specimens from patients; however, the sensitivity of the visualization of fungi is low, indicating that serological tests are used for early diagnosis. The double-immunodiffusion test (ID) is the “gold standard” test for serology in PCM, although the execution of this test requires the availability of laboratorial infrastructure. We report the improved performance of a latex agglutination test (LAT) by pretreating 30 serum samples from PCM patients and 71 controls (histoplasmosis and aspergillosis patients, patients with bacterial infections, and normal human sera) with a dilution buffer incubated at 37°C for 30 min. The sensitivity and specificity of the LAT test in the nonpretreated samples were 73% and 79%, respectively. However, when samples were pretreated, the sensitivity and specificity of the test increased to 90%. In this study, we did not observe cross-reactivity with histoplasmosis patient sera, but some reactions to sera from patients with aspergillosis and bacterial infections were noted. Normal human sera were not reactive in our tests. These results indicate the need for the elimination of heterologous reactions so that we can adequately use this method for screening cases of PCM.

scholarly journals Predicting the Course of Graves’ Orbitopathy Using Serially Measured TSH-Receptor Autoantibodies by Automated Binding Immunoassays and the Functional Bioassay

2021 ◽  
Vol 53 (07) ◽  
pp. 435-443
Author(s):  
Svenja Philipp ◽  
Anja Eckstein ◽  
Mareile Stöhr ◽  
Michael Oeverhaus ◽  
Simon D. Lytton ◽  
...  
Keyword(s):  
Disease Onset ◽  
Added Value ◽  
Tsh Receptor ◽  
Clinical Activity ◽  
Serum Samples ◽  
Severity Scores ◽  
A Cell ◽  
Graves Orbitopathy ◽  
Serial Serum

AbstractThe aim of the study was to investigate the use of serial measurements of TSH-receptor autoantibodies (TRAb) with the newest available assay technology to predict the course of Graves’ Orbitopathy (GO) during the first 24 months from disease onset. Serial serum samples from patients with GO (103 mild/135 severe) were collected between 2007 and 2017 and retrospectively analyzed. The course of GO were classified into mild/severe 12 months after manifestation (severe: NOSPECS≥5; mild<5). TRAb were measured with automated binding immunoassays (IU/l): TRAb Elecsys (Cobas, Roche), TRAb bridge assay (IMMULITE, Siemens), and a cell-based bioassay (percent of specimen to reference ratio - SRR%) (Thyretain, Quidel). Variable cut off levels of measured TRAb were calculated at specificity of 90% from receiver operator curve (ROC) analysis for several timepoints during the course of GO. To select one: 5–8 months after first GO symptoms, which is the timepoint for usual referals for treatment mild course could be predicted at cut offs of 1.5 IU/l (Elecsys), 0.8 IU/l (Immulite) and 402% SRR (Thyretain) and the risc of severe course has to be anticipated if TRAb are above 11.6 IU/l (Elecsys), 6.5 IU/l (Thyretain), and 714% SRR (Thyretain). The Thyretain bioassay showed the highest diagnostic sensitivity (using the commercial cut off’s) over the entire follow up period. TRAb measurements during the 24-month follow up of GO provide added value to the GO clinical activity and severity scores and should be used especially in the event of an unclear decision-taking situation with regard to therapy.

Free light chains and heavy/light chains in monitoring POEMS patients

2016 ◽  
Vol 54 (6) ◽  
Author(s):  
Sara Altinier ◽  
Kozeta Proko ◽  
Martina Zaninotto ◽  
Daniela Ciubotaru ◽  
Mara Seguso ◽  
...  
Keyword(s):  
Poems Syndrome ◽  
Light Chains ◽  
Vascular Endothelial ◽  
Free Light Chains ◽  
Serum Samples ◽  
Period Range ◽  
Endothelial Growth Factor ◽  
The Relationship

AbstractPOEMS syndrome is defined by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes. The vascular endothelial growth factor (VEGF) appears to play a key role in the pathogenesis of the syndrome, and its concentrations are deemed to correlate to disease activity. The aim of the present study was to verify whether other biochemical markers including serum free light chains (FLC) and heavy/light chains (HLC) would be of value in monitoring POEMS patients.Fifty-three serum samples were collected from seven POEMS patients at diagnosis and during a follow-up period (range 14–56 months). VEGF was measured using an ELISA method, while FLC and HLC concentrations were measured using Binding Site reagents on a BNII (Siemens) nephelometer.At diagnosis all patients presented high VEGF concentrations, while the κ/λFLC ratio (FLCr) was within the reference range. Four patients had abnormal HLC, HLCκ/HLCλ (HLCr) and FLC values. The relationship between the trend of VEGF and both HLC and FLC during the follow-up was analysed by means of Cohen’s κ coefficient. VEGF and HLC values displayed a significant κ-Cohen (0.537, p=0.002) in all chemotherapy-responder patients while in non-responders it did not. Conversely, in both responders and non-responders, VEGF and FLC values did not attain a significance on κ-Cohen analysis. In three out of four responders HLCr values increased, thus reflecting an improved clinical condition.The findings made in the present study indicate that HLC, either as intact immunoglobulin or as HLCr, may provide useful information, particularly in identifying responders and confirm that the role of FLC is unreliable in monitoring patients with POEMS syndrome.

scholarly journals Antibody response in patients with Gaucher disease after repeated infusion with macrophage-targeted glucocerebrosidase

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1402-1409 ◽  
Author(s):  
SM Richards ◽  
TA Olson ◽  
JM McPherson
Keyword(s):  
Gaucher Disease ◽  
Mean Value ◽  
Patient Treatment ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Enzyme Replacement ◽  
Human Sera ◽  
Normal Human ◽  
Igg1 Subclass

Recent clinical data have shown that enzyme replacement therapy with macrophage-targeted glucocerebrosidase (GCR) can be effective in treating type 1 Gaucher disease. Sera from 262 patients, repeatedly infused with GCR, were assessed for the presence of antibodies to this therapeutic protein. Patient serum samples obtained at 3-month intervals were assessed by enzyme-linked immunosorbent assay and those with values greater than two standard deviations above the mean value obtained with a pool of normal human sera were further characterized by radioimmunoprecipitation. At the time of these analyses, the duration of patient treatment varied from 3 months to approximately 3 years. Of the 262 patients analyzed, 34 (12.9%) showed IgG antibodies, as confirmed by radioimmunoprecipitation. All patients who seroconverted did so within 1 year of treatment. The predominant antibody developed was the IgG1 subclass. Fourteen patients in the study experienced periodic symptoms suggestive of immediate hypersensitivity. Nine of these 14 patients had antibody to GCR as determined by radioimmunoprecipitation, whereas 5 patients were antibody negative. There was no evidence of the development of IgE antibodies in these 14 patients. The presence of GCR antibodies did not appear to effect efficacy of therapy in any of the patients treated to date.

scholarly journals Antibody against influenza A2 virus neuraminidase in human sera

1969 ◽  
Vol 67 (2) ◽  
pp. 353-365 ◽  
Author(s):  
G. C. Schild ◽  
R. W. Newman
Keyword(s):  
Influenza A ◽  
Complement Fixation ◽  
Haemagglutination Inhibition ◽  
Vaccine Trial ◽  
Research Centre ◽  
Influenza A Viruses ◽  
Serum Samples ◽  
The Public ◽  
Human Sera ◽  
Serial Serum

SUMMARY1. High titres of neuraminidase-inhibiting antibody were detected in convalescent human sera following natural influenza A2 infections.2. Such antibody was encountered infrequently in acute serum samples. Antibody persisted only 5–6 months after infection in the four individuals from whom serial serum specimens were available.3. Following immunization with killed influenza virus vaccines (with adjuvant) neuraminidase inhibiting antibody was detected in human sera. The titres were in general lower than those detected in convalescent human sera.4. The specificity of the neuraminidase-inhibiting antibody in human and animal antisera was studied. Tests with convalescent human sera using purified neuraminidase preparations and with a recombinant virus containing A2 neuraminidase and haemagglutinin distinct from that of human influenza A viruses enabled the conclusion that the antibody detected was specific for influenza A 2 neuraminidase.We wish to thank Dr D. A. J. Tyrrell of the Clinical Research Centre, Mill Hill, London, for human serum specimens, Dr D. Breeze of Evans Medical Ltd., Liverpool, for sera from an influenza vaccine trial and Dr M. S. Pereira of the Public Health Laboratory, Colindale, London, for serial serum samples from persons who had influenza in 1957. Dr M. S. Pereira carried out the haemagglutination-inhibition tests and complement fixation tests on these sera.We are grateful to Dr H. G. Pereira and Dr D. A. J. Tyrrell for valuable discussions during the course of this study, and to Professor C. H. Stuart-Harris for his comments on the manuscript.

Relationship between Thyroglobulin and Tumor Detectabilily with Thallium-201 in Differentiated Thyroid Cancer

2000 ◽  
Vol 39 (01) ◽  
pp. 10-15 ◽  
Author(s):  
S. P. Müller ◽  
Ch. Reiners ◽  
A. Bockisch ◽  
Katja Brandt-Mainz
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Roc Analysis ◽  
Tsh Suppression ◽  
Significant Difference ◽  
Test Specificity ◽  
The Relationship ◽  
Tumor Scintigraphy ◽  
Tsh Stimulation

Summary Aim: Tumor scintigraphy with 201-TICI is an established diagnostic method in the follow-up of differentiated thyroid cancer. We investigated the relationship between thyroglobulin (Tg) level and tumor detectability. Subject and methods: We analyzed the scans of 122 patients (66 patients with proven tumor). The patient population was divided into groups with Tg above (N = 33) and below (N = 33) 5 ng/ml under TSH suppression or above (N = 33) and below (N = 33) 50 ng/ml under TSH stimulation. Tumor detectability was compared by ROC-analysis (True-Positive-Fraction test, specificity 90%). Results: There was no significant difference (sensitivity 75% versus 64%; p = 0.55) for patients above and below 5 ng/ml under TSH suppression and a just significant difference (sensitivity 80% versus 58%; p = 0.04) for patients above and below 50 ng/ml under TSH stimulation. In 18 patients from our sample with tumor, Tg under TSH suppression was negative, but 201-TICI-scan was able to detect tumor in 12 patients. Conclusion: Our results demonstrate only a moderate dependence of tumor detectability on Tg level, probably without significant clinical relevance. Even in patients with slight Tg elevation 201-TICI scintigraphy is justified.

Anticardiolipin Antibodies Are Elevated in HIV-1 Infected Haemophiliacs but Do Not Predict for Disease Progression

1989 ◽  
Vol 61 (01) ◽  
pp. 081-085 ◽  
Author(s):  
Simon Panzer ◽  
Christoph Stain ◽  
Hubert Hartl ◽  
Robert Dudczak ◽  
Klaus Lechner
Keyword(s):  
Normal Values ◽  
Anticardiolipin Antibodies ◽  
Haemophilia A ◽  
Serum Samples ◽  
Factor Viii Concentrates ◽  
Patient Groups ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Cd4 Lymphocytes

SummaryLevels of anticardiolipin antibodies (ACA) were measured in 55 patients with haemophilia A in serum samples obtained in 1983 and in 1987. Twenty-one patients were negative for anti HIV-1 antibodies in 1983 and remained negative in 1987; 34 patients had anti HIV-1 antibodies in 1983; 17 of these latter patients remained asymptomatic, whereas 17 patients developed ARC or AIDS during the 4 years follow-up. Thirteen anti HIV-1 negative patients had elevated ACA levels in 1983; subsequently, a significant decrease was observed in all these subjects (p <0.001). All anti HIV-1 positive patients had elevated ACA levels in 1983; normal values were found in 9 patients in 1987. Yet, these changes were not significant (p >0.05). ACA levels were significantly higher in HIV-1 infected patients than in those without anti HIV-1 antibodies (p <0.05). There was no difference of ACA levels between the two anti HIV-1 positive patient groups, be it in 1983 or be it in 1987 (p >0.05). There was no correlation of ACA levels with serum IgG concentrations, CD4+ lymphocytes, or the consumption of factor VIII concentrates.

IMMUNOLOGICAL REACTIVITY OF INSULIN IN HUMAN SERUM

1966 ◽  
Vol 53 (4) ◽  
pp. 673-680 ◽  
Author(s):  
Torsten Deckert ◽  
Kai R. Jorgensen
Keyword(s):  
Normal Subjects ◽  
The Other ◽  
Human Pancreas ◽  
Porcine Pancreas ◽  
Crystalline Insulin ◽  
Endogenous Insulin ◽  
Significant Difference ◽  
Human Sera ◽  
Normal Human ◽  
The One

ABSTRACT The purpose of this study was to investigate whether a difference could be demonstrated between crystalline insulin extracted from normal human pancreas, and crystalline insulin extracted from bovine and porcine pancreas. Using Hales & Randle's (1963) immunoassay no immunological differences could be demonstrated between human and pig insulin. On the other hand, a significant difference was found, between pig and ox insulin. An attempt was also made to determine whether an immunological difference could be demonstrated between crystalline pig insulin and crystalline human insulin from non diabetic subjects on the one hand and endogenous, circulating insulin from normal subjects, obese subjects and diabetic subjects on the other. No such difference was found. From these experiments it is concluded that endogenous insulin in normal, obese and diabetic human sera is immunologically identical with human, crystalline insulin from non diabetic subjects and crystalline pig insulin.

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