Mellitus, LLC reported the publication of results from a prospective, investigator-initiated study conducted at Brigham and Women’s Hospital (BWH) demonstrating the potential clinical utility of glycated CD59 (GCD59) as a novel biomarker for the screening and diagnosis of gestational diabetes mellitus (GDM). The data from this study showed that a single blood test that measures plasma GCD59 at week 24-28 of gestation identified women with GDM with high sensitivity and specificity. The study was completed by a team of investigators at BWH led by Jose A. Halperin, M.D., in collaboration with researchers from Harvard T.H. Chan School of Public Health. Dr. Halperin, scientific Co-founder of Mellitus, is a physician and researcher at BWH and Associate Professor of Medicine at Harvard Medical School (HMS).
Gestational Diabetes Mellitus (GDM), also known as diabetes in pregnancy, is a major cause of adverse pregnancy outcomes for both babies and mothers. Babies born from mothers with GDM tend to be large for their gestational age (LGA). Delivery of LGA babies is the main cause of the many complications associated with GDM, including pre-term birth, foetal injury, perinatal mortality and required caesarean delivery. GDM also increases the mother’s risk of preeclampsia and gestational hypertension.
Because treatment of GDM mitigates the risk of complications, practice guidelines from professional organizations such as the American College of Obstetrics and Gynaecology and the American Diabetes Association recommend screening of all non-diabetic pregnant women for GDM. Approximately four million pregnant women are screened for GDM each year in the United States in accordance with these practice guidelines. Currently, the standard of care predominantly uses a two-step approach. The first step is administration of the Glucose Challenge Test (GCT); in this test, blood sugar is measured one-hour after drinking a glucose solution. If a woman has a positive GCT test, she is reflexed to having a second test, an Oral Glucose Tolerance Test (OGTT). The OGTT serves to diagnose GDM. The OGTT requires women to fast overnight prior to having a blood draw, followed by drinking a glucose solution and additional blood tests every hour for three hours. These tests are time consuming, uncomfortable for the patients and are reported to have poor reproducibility. Other tests that measure HbA1c or fructosamine are not sensitive and therefore not routinely used during prenatal care to screen and diagnose GDM. Issues associated with screening and diagnosing GDM highlight the need for an accurate, simpler and more patient-friendly test for GDM.
The protein known as CD59 is an inhibitor of the complement system that is inactivated by high glucose in diabetes to form glycated CD59 (GCD59). Inactivation of CD59 decreases its protective effect and promotes complement-mediated damage that reportedly plays a role in the processes leading to complications of diabetes such as nephropathy, neuropathy and retinopathy.
The study published evaluated levels of GCD59 in plasma samples from 1,000 women undergoing routine screening and diagnosis of GDM at week 24-28 of gestation at Brigham and Women’s Hospital in Boston. 500 of the samples were from women who had a normal GCT (controls) and another 500 were from women who had failed the GCT and completed a subsequent OGTT (cases). Of the cases, 127 were diagnosed with GDM. The primary objective of the study was to assess the accuracy of plasma GCD59 to predict the results of the GCT. Secondary aims were to assess the accuracy of plasma GCD59 in predicting the diagnosis of GDM by OGTT and the association of plasma GCD59 with the prevalence of LGA newborns.
The study found that, compared to controls, median levels of plasma GCD59 were 8.5-fold higher in women who failed the GCT and 10-fold higher in women diagnosed with GDM. Results also demonstrated that measurement of plasma GCD59 independently discriminated cases from controls with high sensitivity and specificity, even after adjustment for covariates such as maternal age, BMI, race/ethnicity, multiplicity, gestational age and previous history of diabetes. More detailed results can be found in the Diabetes Care paper.
"This is the first study to demonstrate that a single measurement of plasma GCD59 can be used as a simplified method to identify women who would have failed a GCT and are at higher risk of GDM," said Dr. Halperin. "These results indicate that measurement of this novel disease-associated biomarker may be a convenient and effective alternative to the cumbersome methods currently used to screen and diagnose GDM; the study opens the door to future multi-center studies to confirm the clinical utility of plasma GCD59 as a biomarker for detection and diagnosis of GDM."

EurekAlert
www.eurekalert.org/pub_releases/2017-04/mbci-ssg042517.php

Misfolded proteins associated with Parkinson’s disease were detected in cerebrospinal fluid by scientists at McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), paving the way to development of a biochemical test for the diagnosis of the disease.
The research was led by Claudio Soto, Ph.D., professor in the Department of Neurology and the director of the George and Cynthia Mitchell Center for Alzheimer’s disease and Related Brain Disorders at UTHealth.
Parkinson’s disease (PD) is a degenerative disorder of the brain that initially affects motor skills, causing tremors, stiffness, slowness of movement and impaired balance. As it progresses, patients may develop cognitive problems, psychiatric alterations and dementia. There are no current laboratory or blood tests that have been proven to help in diagnosis. Because the disease can be difficult to diagnose accurately, diagnosis is sometimes made by ruling out other neurological diseases.
Using a technology developed by Soto that was shown in previous studies to detect misfolded proteins associated with diseases such as Creutzfeld-Jacob and Alzheimer’s disease, researchers targeted misfolded alpha-synuclein (aSyn) aggregates as a way of developing a sensitive biochemical diagnosis for PD. The Protein Misfolding Cyclic Amplification (PMCA) technology was able to detect very small amounts of the misfolded protein circulating in cerebrospinal fluid.
“Of significant interest is that the amount of aSyn detected correlates with the severity of the disease and in two of the control samples, aSyn was detected and those people later developed clinical symptoms of PD,” Soto said.
The research included blind screenings of cerebrospinal fluid of two cohorts of 76 PD patients, as well as controls of 65 people who were healthy or affected by other neurological disorders, 18 affected by neurodegenerative diseases and 14 affected by Alzheimer’s disease.
Since cerebrospinal fluid is removed through spinal taps, which are invasive and painful, the hope is that future research would enable optimization of the PMCA assay to detect aSyn in blood or urine.
“The hope is that we could use aSyn- PMCA to detect PD in patients before they develop symptoms, and those patients could be entered into clinical trials for novel treatments that might prevent, cure or delay the progression of the disease before substantial and irreversible damage of the brain,” Soto said.

The University of Texas Health Science Center at Houston http://tinyurl.com/j98zslw

An in-depth computational analysis of genetic variants implicated in both schizophrenia and rheumatoid arthritis by researchers at the University of Pittsburgh points to eight genes that may explain why susceptibility to one of the disorders could place individuals at lower risk for the other.

“There is a wealth of genomic data on both schizophrenia and rheumatoid arthritis. Analysing it jointly with known protein interaction information could provide invaluable clues to the relationship between the diseases and also shed light on their shared roots,” said Madhavi Ganapathiraju Ph.D., associate professor of biomedical informatics at the University of Pittsburgh School of Medicine and senior author of the study.

While schizophrenia is a psychiatric disorder of unknown origin and rheumatoid arthritis is an autoimmune disease of the joints that occurs as a result of the body’s immune system attacking its own cells, both disorders are thought to be influenced by multiple genetic risk factors modified by the environment.

“Several previous research studies have hinted at a potential inverse relationship in the prevalence and risk for the two disorders, so we wondered if individual genetic variants may exist that could have opposing effects on the risk of schizophrenia and rheumatoid arthritis,” said co-senior author Vishwajit Nimgaonkar M.D., Ph.D., professor of psychiatry at Pitt’s School of Medicine and human genetics at Pitt’s Graduate School of Public Health.

The researchers first analysed two large databases of genetic variants significantly associated with either schizophrenia or rheumatoid arthritis. They identified 18 unique variants, also known as single nucleotide polymorphisms (SNPs) that were located in the HLA region of the genome that harbours genes associated with immune function. The variants appeared to confer different risk for schizophrenia or rheumatoid arthritis. As the SNPs were located near eight known genes in this region, the authors suggested those genes might lead to dysfunction in both schizophrenia and rheumatoid arthritis. Proteins encoded by two of these eight genes, HLA-B and HLA-C, are present in both brain and immune cells.

Analysis of proteins that interact with these eight genes using a computational model developed last year by Ganapathiraju’s team called High-Precision Protein Interaction Prediction found more than 25 signalling pathways with proteins common to both rheumatoid arthritis and schizophrenia signalling. Moreover, several of these pathways were associated with immune system function and inflammation.

The findings are encouraging because they support associations of the HLA gene region and immune function with schizophrenia and rheumatoid arthritis that were known over four decades ago, said Ganapathiraju.

Increasing evidence also suggests that a dysfunctional immune system could play a role in the development of schizophrenia.

University of Pittsburghwww.upmc.com/media/NewsReleases/2017/Pages/bioinformatics-study.aspx

Shimadzu has introduced its European Innovation Center in Duisburg, Germany. This innovations-oriented Think Tank combines academic-scientific and technological know-how to use Shimadzu’s expertise to provide even more customer-focused service.  It merges the cutting-edge analytical technologies of Shimadzu with the game-changing topics in markets and science covered by opinion leaders, strategic thinkers and scientific experts in order to create new solutions for tomorrow.  With their leading-edge research expertise, highly-reputed scientists from well-known European universities contribute to the Shimadzu European Innovation Center. Their scientific focus areas include clinical applications, imaging technology, food, and composites with an emphasis on new methods, tools, techniques, diagnostics, and solutions. Their work will, for example, further facilitate bridging the gap between analytical and medical research, and further improve patients’ health as well as consumer and environmental protection.
Shimadzu analysers involved in the European scientists’ research projects in particular include liquid chromatography, LC-MS, material testing, and life sciences.
www.shimadzu.eu/

1 000 new mutations in the blood group genes: that is what physician and former programmer Mattias Möller found in his research study in which he developed new software and investigated blood group genes in 2 504 people.

The international project 1000 Genomes is so far the world’s largest mapping of human genetic variants. By creating a new computer program, Mattias Möller processed the genomes of 2 504 people. He imported these genomes to his newly developed database Erythrogene, and matched them against previously known genetic variants. The result was the discovery of 1 000 hitherto unknown mutations which could have a negative effect in the case of blood transfusions, for example.

“Never before has there been a worldwide mapping of blood group genes in healthy individuals. Most previously known blood group variants were discovered when a blood transfusion failed, i.e. when it didn’t work between the donor and the recipient. I started from the genes instead, to find variations in DNA which might give rise to a new antigen, likely to cause problems in case of transfusion, for example”, explains Mattias Möller, doctoral student at the Department of Laboratory Medicine.

On the surface of the red blood cells are proteins and sugar molecules, in which small differences give rise to different antigens. The ability to identify and match blood group types is important for blood transfusions, but also in pregnancy and before certain types of transplantation. A transfusion with mismatched blood can lead to a transfusion reaction. This type of reaction can be mild and barely noticeable, or so strong that the blood cells rupture and, in the worst cases, the patient dies.

Mattias Möller’s study showed that 89 per cent of the genetic variants were previously known, but among the remaining 11 per cent were a total of 1 000 different mutations which were absent from official catalogues of known blood group variants.

“Of course not all variants lead to new antigens. But we need to go on and conduct further analyses to investigate how the genetic expression changes, i.e. how the molecules on the surface of the cell are affected.ˮ

There are currently 352 mapped antigens, but the research has so far mainly focused on populations in Europe and North America. A future research field is Africa, where there is greater variation between different population groups. As research on African populations increases, in combination with blood transfusions becoming more common there, many new antigens are likely to be discovered.

Lund Universitywww.lunduniversity.lu.se/article/how-1-000-new-genetic-variants-were-discovered-in-blood-groups