scholarly journals Changes of Serum IgG Glycosylation Patterns in Primary Biliary Cholangitis Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoli Zeng ◽  
Siting Li ◽  
Shiyi Tang ◽  
Xi Li ◽  
Guoyuan Zhang ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Glycan Structure ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Reliable Technique ◽  
Lectin Microarray ◽  
Serum Igg ◽  
Lectin Blot ◽  
The Difference ◽  
Igg Glycosylation

ObjectivePrimary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease whose diagnosis is based significantly on autoantibody detection. This study aims to investigate the glycosylation profile of serum IgG in PBC patients using high-throughput lectin microarrays technology.MethodLectin microarray containing 56 lectins was used to detect and analyze the expression of serum IgG glycosylation in 99 PBC patients, 70 disease controls (DCs), and 38 healthy controls (HCs). Significant differences in PBC from control groups as well as across PBC subgroups positive for various autoantibodies were explored and verified by lectin blot technique.ResultsLectin microarray detection revealed that compared to DC and HC groups, the specific glycan level of serum IgG sialic acid in PBC patients was increased. For each PBC subgroup, glycan levels of IgG mannose and galactose were decreased in AMA-M2 positive PBC patients compared to the AMA-M2 negative group. IgG N-Acetylgalactosamine (GalNAc) and fucose were decreased in anti-sp100 positive patients. IgG galactose was increased in anti-gp210 positive patients. IgG mannose was decreased in ACA-positive patients. Although the difference in overall sialic acid level was not observed using lectin blot, all results among the above PBC subgroups were consistent with the results of the technique.ConclusionLectin microarray is an effective and reliable technique for analyzing glycan structure. PBC patients positive for different autoantibody exhibits distinct glycan profile. Altered levels of glycosylation may be related to the occurrence and development of the disease, which could provide a direction for new biomarker identification.

scholarly journals Variability of serum IgG sialylation and galactosylation degree in women with advanced endometriosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katarzyna Sołkiewicz ◽  
Hubert Krotkiewski ◽  
Marcin Jędryka ◽  
Ewa M. Kratz
Keyword(s):  
Cluster Analysis ◽  
Sialic Acid ◽  
Control Group ◽  
Clinical Tool ◽  
Non Invasive ◽  
Healthy Women ◽  
Serum Igg ◽  
And Cluster Analysis ◽  
Invasive Diagnostics ◽  
And Control

AbstractEndometriosis is an inflammatory disease which diagnostics is difficult and often invasive, therefore non-invasive diagnostics methods and parameters are needed for endometriosis detection. The aim of our study was to analyse the glycosylation of native serum IgG and IgG isolated from sera of women classified as: with endometriosis, without endometriosis but with some benign ginecological disease, and control group of healthy women, in context of its utility for differentiation of advanced endometriosis from the group of healthy women. IgG sialylation and galactosylation/agalactosylation degree was determined using specific lectins: MAA and SNA detecting sialic acid α2,3- and α2,6-linked, respectively, RCA-I and GSL-II specific to terminal Gal and terminal GlcNAc, respectively. The results of ROC and cluster analysis showed that the serum IgG MAA-reactivity, sialylation and agalactosylation factor may be used as supplementary parameters for endometriosis diagnostics and could be taken into account as a useful clinical tool to elucidate women with high risk of endometriosis development. Additionally, we have shown that the analysis of native serum IgG glycosylation, without the prior time-consuming and expensive isolation of the protein, is sufficient to differentiation endometriosis from a group of healthy women.

scholarly journals Widespread gaps in the quality of care for primary biliary cholangitis in UK

2021 ◽  
pp. flgastro-2020-101713
Author(s):  
Mathuri Sivakumar ◽  
Akash Gandhi ◽  
Eathar Shakweh ◽  
Yu Meng Li ◽  
Niloufar Safinia ◽  
...  
Keyword(s):  
Quality Of Care ◽  
Medical Records ◽  
Clinical Symptoms ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Patient Demographics ◽  
Risk Patients ◽  
Wide Scale ◽  
The Uk

ObjectivePrimary biliary cholangitis (PBC) is a progressive, autoimmune, cholestatic liver disease affecting approximately 15 000 individuals in the UK. Updated guidelines for the management of PBC were published by The European Association for the Study of the Liver (EASL) in 2017. We report on the first national, pilot audit that assesses the quality of care and adherence to guidelines.DesignData were collected from 11 National Health Service hospitals in England, Wales and Scotland between 2017 and 2020. Data on patient demographics, ursodeoxycholic acid (UDCA) dosing and key guideline recommendations were captured from medical records. Results from each hospital were evaluated for target achievement and underwent χ2 analysis for variation in performance between trusts.Results790 patients’ medical records were reviewed. The data demonstrated that the majority of hospitals did not meet all of the recommended EASL standards. Standards with the lowest likelihood of being met were identified as optimal UDCA dosing, assessment of bone density and assessment of clinical symptoms (pruritus and fatigue). Significant variations in meeting these three standards were observed across UK, in addition to assessment of biochemical response to UDCA (all p<0.0001) and assessment of transplant eligibility in high-risk patients (p=0.0297).ConclusionOur findings identify a broad-based deficiency in ‘real-world’ PBC care, suggesting the need for an intervention to improve guideline adherence, ultimately improving patient outcomes. We developed the PBC Review tool and recommend its incorporation into clinical practice. As the first audit of its kind, it will be used to inform a future wide-scale reaudit.

Cholestatic Liver Injury: Care of Patients With Primary Biliary Cholangitis or Primary Sclerosing Cholangitis

2016 ◽  
Vol 27 (4) ◽  
pp. 441-452 ◽  
Author(s):  
Laurie Larson ◽  
Michelle James ◽  
Andrea Gossard
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Disease Recurrence ◽  
Outpatient Setting ◽  
Primary Biliary Cholangitis ◽  
Malignant Neoplasms ◽  
Cholestatic Liver Disease ◽  
Gallbladder Polyps ◽  
Increased Risk ◽  
Common Causes

The most common causes of chronic cholestatic liver disease are primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Both disease processes are characterized by a destruction of intrahepatic and/or extrahepatic biliary ducts. The etiology is not entirely clear; however, there is an underlying autoimmune component contributing to both disease processes. Although PBC and PSC are often diagnosed and managed in the outpatient setting, in some instances, a patient may have jaundice, fatigue, and pruritus requiring evaluation and determination of the cholestatic cause. Patients with PSC should be monitored for evidence of cholangiocarcinoma, colon cancer, and gallbladder polyps as they are at an increased risk of malignant neoplasms. Liver transplant has the potential for improving quality of life, although disease recurrence is a risk.

Establishing Reliability Criteria for Liver ElastPQ Shear Wave Elastography (ElastPQ-SWE): Comparison Between 10, 5 and 3 Measurements

2019 ◽  
Author(s):  
Davide Roccarina ◽  
Laura Iogna Prat ◽  
Elena Buzzetti ◽  
Marta Guerrero Misas ◽  
Francesco Marcello Aricó ◽  
...  
Keyword(s):  
Liver Disease ◽  
Diagnostic Performance ◽  
Liver Stiffness ◽  
Quality Criterion ◽  
Quality Criteria ◽  
Shear Wave Elastography ◽  
Primary Biliary Cholangitis ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
The Difference

Abstract Purpose ElastPQ is a new elastography technique for non-invasive liver fibrosis staging. However, it does not have validated reliability criteria. We tested the reliability of a different number of measurements in patients with chronic liver disease and explored whether the application of quality criteria improves the diagnostic performance. Materials and Methods All patients underwent liver stiffness assessment (LSM) with ElastPQ and Fibroscan (F-TE). The mean, median, standard deviation (SD) and interquartile range (IQR) of 10, 5 and 3 measurements were retrospectively collected for each patient and compared to each other. Liver histology was available in a subset of patients. Results Overall, 400 patients met the inclusion criteria. Non-alcoholic fatty liver disease (NAFLD) was the most represented etiology (75 %), followed by primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). The correlation of medians was significantly better between 10 and 5 measurements than between 10 and 3. The difference of medians was significant only in the comparison between 10 and 3 measurements. The correlation between ElastPQ and F-TE was equally good for 10 and 5 measurements and significantly improved after an IQR/median ≤ 30 % was applied. The diagnostic performance of ElastPQ was better with the median value of 10 and 5 measurements and improved if LSM values were obtained with IQR/M ≤ 30 %. Conclusion The median value of 5 valid LSMs suffices for the reliable estimation of liver stiffness using ElastPQ. The quality criterion of IQR/M ≤ 30 % should also be followed when using this technique.

Splanchnic hemodynamics in portal-hypertensive rats: measurement with gamma-labeled microspheres

1982 ◽  
Vol 242 (2) ◽  
pp. G156-G160 ◽  
Author(s):  
R. J. Groszmann ◽  
J. Vorobioff ◽  
E. Riley
Keyword(s):  
Blood Flow ◽  
Portal Vein ◽  
Experimental Models ◽  
Hypertensive Rats ◽  
Venous Flow ◽  
Reliable Technique ◽  
Splanchnic Hemodynamics ◽  
Significant Difference ◽  
Normal Rat ◽  
The Difference

A method to quantitate hepatic arterial flow (HA), portal venous flow (PBF), and blood flow through portal-systemic shunts (ShBF) in portal-hypertensive rats is described. This method relies on the injection of two differently radiolabeled microspheres (15 micrometers) into the left ventricle and spleen. To evaluate the usefulness of this technique, studies were performed on normal, cirrhotic, and portal vein-ligated rats anesthetized with ketamine. With this method, PBF is calculated indirectly from the sums of the blood flow of the splanchnic organs that drain into the portal vein. In the portal-hypertensive animals with portal-systemic shunting, this technique allows for the determination of PBF perfusing the liver [hepatic fraction of portal flow (HFP)] and PBF escaping through portal-systemic shunts (ShBF). The portal vein-ligated rats have higher HA flow (0.68 +/- 0.08 ml . min-1 . g-1) and lower HFP (0.08 +/- 0.01 ml . min-1 . g-1) than either the cirrhotic (HA: 0.27 +/- 0.03 ml . min-1 . g-1, P less than 0.01; HFP: 1.20 +/- 0.20 ml . min-1 . g-1, P less than 0.01) or the normal rat (HA: 0.29 +/- 0.06 ml . min-1 . g-1, P less than 0.01; HFP: 1.39 +/- 0.16 ml . min-1 . g-1, P less than 0.01). No significant difference was found between the cirrhotic and normal rats. The ShBF was higher in the portal vein-ligated rats (21.4 +/- 2.8 ml/min) than in the cirrhotic (4.6 +/- 2.5 ml/min, P less than 0.001) or normal rats (0.03 +/- 0.005 ml/min, P less than 0.01). The difference between the cirrhotic and normal animals was also significant (P less than 0.05). This is a simple, rapid, and reliable technique that allows for the quantitation of splanchnic hemodynamics in experimental models with portal hypertension.

scholarly journals Practical strategies for pruritus management in the obeticholic acid-treated patient with PBC: proceedings from the 2018 expert panel

2019 ◽  
Vol 6 (1) ◽  
pp. e000256 ◽  
Author(s):  
Jennifer Pate ◽  
Juilo A Gutierrez ◽  
Catherine T Frenette ◽  
Aparna Goel ◽  
Sonal Kumar ◽  
...  
Keyword(s):  
Liver Disease ◽  
Patient Adherence ◽  
Treated Patient ◽  
Management Strategies ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Common Symptom ◽  
Obeticholic Acid ◽  
Intrahepatic Bile Ducts ◽  
Patient Health

Background and aimsThis article provides expert guidance on the management of pruritus symptoms in patients receiving obeticholic acid (OCA) as treatment for primary biliary cholangitis (PBC). PBC is a chronic, autoimmune cholestatic liver disease that affects intrahepatic bile ducts. If not adequately treated, PBC can lead to cholestasis and end-stage liver disease, which may require transplant. Timely treatment is therefore vital to patient health. Pruritus is a common symptom in patients with PBC. Additionally, the use of OCA to treat PBC can contribute to increased pruritus severity in some patients, adding to patient discomfort, decreasing patient quality of life (QoL), and potentially affecting patient adherence to OCA treatment.MethodsIn May 2018, a group of physician experts from the fields of gastroenterology, hepatology, and psychiatry met to discuss the management of pruritus in OCA-treated patients with PBC. Recognizing the importance of optimizing treatment for PBC, these experts developed recommendations for managing pruritus symptoms in the OCA-treated PBC patient based on their experience in clinical practice.ResultsThese recommendations include a comprehensive list of management strategies (including over-the-counter, prescription, and alternative therapies), guidance on titration of OCA to minimize pruritus severity, and an algorithm that outlines a practical approach to follow up with patients receiving OCA, to better assess and manage pruritus symptoms.ConclusionsPruritus associated with OCA therapy is dose dependent and often manageable, and with the proper education and tools, most pruritus cases can be effectively managed to minimize treatment discontinuation.

THE EFFECT OF SIALIDASE ON PIG TRANSFERRINS

1963 ◽  
Vol 41 (1) ◽  
pp. 2523-2527 ◽  
Author(s):  
F. K. Kristjansson ◽  
J. D. Cipera
Keyword(s):  
Sialic Acid ◽  
Electrophoretic Mobility ◽  
High Voltage ◽  
Migration Rates ◽  
The Difference

1. Sialidase digestion resulted in a decreased electrophoretic mobility of pig transferrins without destroying their ability to bind iron.2. The decrease in electrophoretic mobility occurred in two distinct steps.3. The migration rates of the final sialidase digestion products of TfA and TfB suggest that the difference in mobilities of TfA and TfB is not due to a difference in the amount of sialic acid which each contains.4. The mobility differences between the three zones observed for both TfA and TfB under high voltage Tris–citrate gel analyses do not appear to be due to the amount of sialic acid possessed by each.

Structural Characterization of Baxter's Recombinant Human ADAMTS13 Drug Candidate.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2236-2236
Author(s):  
Alexandra Foettinger-Vacha ◽  
Martin Kaliwoda ◽  
Peter Matthiessen ◽  
Meinhard Hasslacher ◽  
Hanspeter Rottensteiner ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Peptide Mapping ◽  
Degradation Products ◽  
Drug Product ◽  
Sialic Acids ◽  
Drug Candidate ◽  
Order Structure ◽  
Glycan Structure ◽  
Hydrodynamic Diameter ◽  
Sequence Coverage

Abstract Abstract 2236 Baxter has developed a human recombinant (r) ADAMTS13 for treatment of patients with hereditary TTP. The protein is produced in a CHO cell-line using serum and protein-free fermentation technology. The purification process does not use immune-affinity chromatography, and includes two viral reduction steps. The final drug product is formulated without proteins of animal or human origin. Here we characterize preclinical and clinical lots of rADAMTS13 with respect to their structural properties. The molecular weight of rADAMTS13 was determined by MALDI TOF as ∼173 kDa. SDS-PAGE showed one band at ∼190 kDa; no additional distinct protein bands corresponding to other proteins or product related degradation products were visible in the gels. Investigation of the primary structure of rADAMTS13 by peptide mapping revealed a sequence coverage of 98% compared to the theoretical amino acid sequence, and no peptides from the signal or propeptide. Peptide mapping was also used to determine posttranslational modifications of rADAMTS13. Seven O-glycosylation sites were identified in addition to the predicted N-glycosylation, O-fucosylation and C-mannosylation sites. The relative monosaccharide and N-linked oligosaccharides composition was consistent in all preclinical and clinical rADAMTS13 batches. The main N-glycan structure found on rADAMTS13 is a biantennary, core fucosylated complex type oligosaccharide with one or two sialic acids. Quantification of sialic acid determination showed consistent amounts of sialic acid on the terminal ends of the glycans in preclinical and clinical rADAMTS13 samples. N-glycolylneuraminic acid, a potentially immunogenic variant of sialic acid, was <1% the amount of total sialic acids. Higher order structure analysis using dynamic light scattering showed a similar hydrodynamic diameter for all preclinical and clinical lots. Finally, FT-IR and CD analysis showed comparable amounts of α-helix and β-sheet in preclinical and clinical lots. Taken together, similarity was shown between the preclinical and clinical lots of rADAMTS13 in all assays. A phase I clinical trial using rADAMTS13 for the treatment of hereditary TTP patients is expected to start soon. Disclosures: Foettinger-Vacha: Baxter Innovations GmbH: Employment. Kaliwoda:Baxter Innovations GmbH: Employment. Matthiessen:Baxter Innovations GmbH: Employment. Hasslacher:Baxter Innovations GmbH: Employment. Rottensteiner:Baxter Innovations GmbH: Employment. Turecek:Baxter Innovations GmbH: Employment. Mitterer:Baxter Innovations GmbH: Employment. Scheiflinger:Baxter Innovations GmbH: Employment.

scholarly journals Rat mammary-gland transferrin: nucleotide sequence, phylogenetic analysis and glycan structure

1995 ◽  
Vol 307 (1) ◽  
pp. 47-55 ◽  
Author(s):  
H Escrivá ◽  
A Pierce ◽  
B Coddeville ◽  
F González ◽  
M Benaissa ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Mammary Gland ◽  
Sialic Acid ◽  
Amino Acid ◽  
Signal Sequence ◽  
Glycosylation Site ◽  
Glycan Structure ◽  
Sialic Acid Content ◽  
Native Page ◽  
Rat Mammary Gland

The complete cDNA for rat mammary-gland transferrin (Tf) has been sequenced and also the native protein isolated from milk in order to analyse the structure of the main glycan variants present. A lactating-rat mammary-gland cDNA library in lambda gt10 was screened with a partial cDNA copy of rat liver Tf and subsequently rescreened with 5′ fragments of the longest clones. This produced a 2275 bp insert coding for an open reading frame of 695 amino acid residues. This includes a 19-amino acid signal sequence and the mature protein containing 676 amino acids and one N-glycosylation site in the C-terminal domain at residue 490. Phylogenetic analysis was carried out using 14 translated Tf nucleotide sequences, and the derived evolutionary tree shows that at least three gene duplication events have occurred during Tf evolution, one of which generated the N- and C-terminal domains and occurred before separation of arthropods and chordates. The two halves of human melanotransferrin are more similar to each other than to any other sequence, which contrasts with the pattern shown by the remaining sequences. Native rat milk Tf is separated into four bands on native PAGE that differ only in their sialic acid content: one biantennary glycan is present containing either no sialic acid residues or up to three. The complete structures of the two major variants were determined by methylation, m.s. and 400 MHz 1H-n.m.r. spectroscopy. They contain either one or two neuraminic acid residues (alpha 2-->6)-linked to galactose in conventional biantennary N-acetyl-lactosamine-type glycans. Most contain fucose (alpha 1-->6)-linked to the terminal non-reducing N-acetylglucosamine.

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