New research from BRC has found a way to predict rejection of a kidney transplant before it happens, by monitoring the immune system of transplant patients.
The researchers have found that a signature combination of seven immune genes in blood samples can predict rejection earlier than current techniques. Monitoring these markers in transplant patients with regular blood tests could help doctors intervene before any damage to the organ occurs, and improve outcomes for patients.
A renal transplant offers the best treatment for patients whose kidneys have failed, with around 3,000 carried out annually in the UK. Acute rejection occurs when the body’s immune system begins to attack the donated organ. This is a common complication in the first year after the transplant, affecting around 2 in 10 patients. It can affect the lifespan of the transplanted organ.
Currently, acute rejection can only be confirmed by taking a biopsy of the transplanted organ. While acute rejection can be treated, this can only be done when the organ is already affected and damage has already occurred.
Once the new technique is validated further, it has the potential to offer clinicians the use of a simple blood test to predict rejection. Being able to intervene before the event will help prevent damage to patients, and extend the life of the transplanted organ.
Dr Paramit Chowdhury, a consultant nephrologist at Guy’s and St Thomas’ and author on the paper said: “This advance could make a huge difference to our ability to monitor kidney transplant patients and treat rejection earlier. It may also save some patients from an unnecessary biopsy. It is a first step in getting a better insight into the status of a patient’s immune system, allowing better tailoring of the patient’s anti-rejection treatment.
“A big challenge at the moment is that even the best transplanted organ has a limited lifespan of up to 30 years. By being able to pick up signs of rejection early, we might increase the lifespan of the organ and help patients have a better quality of life, for longer.”
The team recruited 455 patients who received a kidney transplant at Guy’s Hospital and followed these patients over the first year of their transplant, collecting regular blood and urine samples. Using these samples and analysing the data over time, they developed a signature combination of seven genes that differentiated patients who developed rejection from those who did not.
They then tested for the signature via a blood test in a separate cohort of patients, and validated that it predicted transplant rejection.
The team also identified a six gene signature for a less common form of complication. BK-virus nephropathy can look clinically similar to acute rejection, but requires a very different therapy – reducing immunosuppression. Being able to distinguish between these complications would mean clinicians can ensure that patients receive the most appropriate treatment.
Dr Maria Hernandez Fuentes, visiting senior lecturer at King’s College London and author on the study, said: “Biomarkers are naturally occurring genes or proteins that appear in the blood, which can tell us what is happening in the body. This is vital in determining the best course of treatment for patients. We were able to monitor the genes that were being expressed in transplant patients and map how these reflected their clinical outcomes.
National Institute for Health Research
Biomedical Research Centre at Guy’shttps://tinyurl.com/y4z9k2c8

QIAGEN and DiaSorin announced the introduction of an automated, CE-marked workflow for QIAGEN’s QuantiFERON-TB Gold Plus blood collection tubes (QFT-Plus BCT) and a novel DiaSorin LIAISON test on widely used immunodiagnostic instruments from DiaSorin. Laboratories in Europe and other markets will now be able to process QFT-Plus BCT, the fourth-generation modern gold standard for latent tuberculosis (TB) detection, with DiaSorin’s flexible, efficient LIAISON systems. Availability is planned for the United States in 2019 and China in 2020.
The LIAISON QuantiFERON-TB Plus Test was developed in a partnership between QIAGEN and DiaSorin to help address accelerating conversion of the global latent TB testing market to the modern blood-based QuantiFERON technology. The launch offers LIAISON customers efficient, high-throughput detection with QFT-Plus as part of the system’s broad content menu, and QFT-Plus customers will gain an option for full automation of laboratory handling to support TB control efforts. More than 7,000 LIAISON systems have been placed worldwide, primarily in hospital laboratories.
“We are pleased to offer customers this compelling, automated solution for the LIAISON QuantiFERON-TB Plus Test, enabling an improved workflow of the world’s leading test for latent TB infection. Increasingly, public health initiatives around the world are using QFT-Plus in screening at-risk patients to safeguard against progression from latent infection to active, life-threatening tuberculosis,” said Thierry Bernard, Senior Vice President, Head of the Molecular Diagnostics Business Area at QIAGEN. “LIAISON users will benefit from adding our unique latent TB test to their laboratory menus and will thereby be able to provide highly accurate screening and novel diagnostic insights. QuantiFERON-TB customers will benefit from LIAISON’s best-in-class, random access, continuous loading and automated workflow. We look forward to working closely with our partners at DiaSorin.”
“I’m really excited about the tremendous opportunity we have in front of us through this alliance with QIAGEN” said Carlo Rosa, Chief Executive Officer of DiaSorin Group. “The collaboration between the two companies can provide a very unique solution to the current LTBI tests demand in the labs all over the world. Our existing LIAISON platforms installed base, combined with the launch of our new CLIA platform, LIAISON XS, in early 2019, will provide new labs the opportunity to approach this relevant testing routine with a very robust and fully-automated solution. I’m convinced that this collaboration with QIAGEN can bring our companies to find additional diagnostic applications where we can leverage on the QuantiFERON technology and the LIAISON installed base, strengthening our positioning in the diagnostic market”.
QuantiFERON assays are based on two components: (1) QuantiFERON blood collection tubes, which contain key components of the test reaction that is uniquely performed in-tube after blood collection; and (2) QuantiFERON test detection, which is used to measure the release of interferon gamma after in-tube incubation. Customers using the new latent TB detection workflow for LIAISON systems will purchase the detection components from DiaSorin and the blood collection tube kits from QIAGEN.
QIAGEN and DiaSorin initiated a collaboration in 2017 to develop new tests for the LIAISON family of analysers based on QIAGEN assay technologies. The QuantiFERON detection workflow is the first to emerge. Additional tests based on QuantiFERON technology, which provides a unique, efficient way to detect asymptomatic infections and other risks that cannot be discovered with standard diagnostic technologies, are planned for adaptation to the LIAISON platforms.
In addition to the partnership with DiaSorin, QIAGEN recently has signed a collaboration agreement with Hamilton Robotics to further improve the automation of QuantiFERON-TB Gold Plus through the integration of Hamilton’s Microlab® STAR™ automated liquid handling workstation into the QFT-Plus assay workflow. This preanalytical automation solution can be potentially combined with DiaSorin instrumentation.
QuantiFERON-TB Gold Plus is registered in more than 75 countries in North America, Europe, Asia, Africa and Latin America. QIAGEN’s QuantiFERON-TB Gold (QFT) and QFT-Plus tests are the market-leading blood tests for latent TB, with faster, less labour-intensive and more accurate insights than the century-old tuberculin skin test. QFT-Plus also has the future potential to deliver increased clinical utility by adding measurement of CD8+ T-cell immune response to detection of CD4+ response. CD8+ T-cells have been shown to play an important role in the development of active TB, and QFT-Plus has been cited by international agencies for its potential benefit among migrants and other populations.
QIAGEN has targeted to exceed 300m in sales with the QuantiFERON portfolio by 2020 and believes its relationship with DiaSorin has both a strategic and financial benefit.
http://www.qiagen.com

Data-driven food allergy diagnostics company, AllerGenis, LLC announced on January 16 that it has entered into a non-exclusive agreement with Luminex Corporation (NASDAQ: LMNX). According to the terms, AllerGenis will have the rights to develop, market and sell its novel precision food allergy diagnostic assay using Luminex’s xMAP® Technology.
The agreement supports the upcoming 2019 commercialization of AllerGenis’ food allergy diagnostic platform, which more than triples diagnostic precision compared to current food allergy tests. AllerGenis’ high-throughput, peptide-bead assay breaks down allergenic proteins into smaller components, called epitopes. It then measures the reactivity of a patient’s antibodies to each epitope to generate a detailed reactivity profile that can provide clinicians a comprehensive solution with accurate information to better assess and manage that patient’s food allergies.
“Adopting Luminex’s bead-based xMAP® technology dramatically increased the power and scope of our food allergy diagnostic,” said Jim Garner, CEO and board member of AllerGenis. “We have been able to scientifically demonstrate the ability to identify food allergies with much higher precision over currently available blood tests. We’re very excited to enter into this agreement with Luminex to bring this much-needed technology to the clinical setting as soon as possible.”
AllerGenis’ peanut allergy assay will be the first product to launch supported by this agreement in the fall of 2019. The company is also developing a pipeline of assays across a wide range of food allergens using its epitope-based technology, as well as novel biomarkers.

Researchers at Vanderbilt University Medical Center and colleagues have identified a gene that increases the risk for a severe and potentially life-threatening reaction to the commonly prescribed antibiotic vancomycin.
Routine testing for this gene could improve patient safety and reduce unnecessary avoidance of other antibiotics, they report.
 “We think this test will be important in the clinical care of patients starting vancomycin and will prevent mortality and short- and long-term complications,” said the paper’s senior author, Elizabeth Phillips, MD.
Vancomycin is commonly given in the hospital or as home intravenous therapy for several weeks in combination with other powerful antibiotics to treat serious and potentially life-threatening bacterial infections.
Within two to eight weeks of initiating antibiotic therapy, however, some patients develop a severe reaction known as DRESS — Drug Rash with Eosinophilia and Systemic Symptoms — characterized by fever, widespread skin rash and internal organ damage caused by an aberrant T-cell mediated immune response to the drug.
When DRESS develops, all treatment is stopped. The mortality rate that results, often from a combination of organ damage, the need for strong immunosuppressants such as steroids and compromised treatment options for the underlying infection, approaches 10 percent.
While the true incidence of DRESS is not known, every year in the United States “hundreds of thousands of patients are at risk,” said Phillips, the John A. Oates Professor of Clinical Research and professor of Medicine, Pharmacology and Pathology, Microbiology and Immunology at VUMC and Vanderbilt University School of Medicine.
For several years, vancomycin has been known to be a common antibiotic trigger for DRESS, however the genetic risk factors predisposing specific patients were not known.
This new finding shows that vancomycin-associated DRESS occurs in patients who carry specific variations in human leukocyte antigen (HLA) genes. HLA genes encode proteins that present foreign peptides (antigens) to T cells (a kind of white blood cell) to stimulate an immune response.
Vanderbilt University Medical Center https://tinyurl.com/y4ukodbb

A Vanderbilt-led research team has discovered genetic variations that increase the risk of heart attack even when patients are receiving a statin drug like Lipitor or Crestor to lower their blood cholesterol.
The finding helps explain why some patients experience a heart attack or the need for coronary revascularization to open blocked heart arteries while taking statins. It suggests that drugs targeting the genetic variations could lower the heart risk in these patients.
The study demonstrates the power of genome-wide association studies and longitudinal electronic health records (EHRs) to find links between genetic variation and disease, said the paper’s first author, Wei-Qi Wei, MD, PhD, assistant professor of Biomedical Informatics in the Vanderbilt University School of Medicine.
Some of the patients were followed for heart disease for up to a decade after starting on their statin drug. The study found that the effect of the genetic variations or variants was independent of how much their cholesterol improved while taking statins.
“People with these genetic variants were at a higher risk for heart disease, even considering those who have ideal cholesterol levels on their statin,” said Joshua Denny, MD, MS, Vice President of Personalized Medicine at Vanderbilt University Medical Center (VUMC) and the paper’s corresponding author.
The researchers searched four sites in the Electronic Medical Records and Genomics (eMERGE) network, a nationwide consortium of experts, biorepositories and electronic medical record systems supported by the National Institutes of Health (NIH), including BioVU, VUMC’s DNA databank.
They found 3,099 people who had experienced a heart attack or the need for revascularization while on statins, and compared them to 7,681 “control” patients on statins who did not experience heart events.
From this comparison, the researchers were able to identify seven genetic variations, called single nucleotide polymorphisms or SNPs, in the LPA locus of genes that were associated with these heart events in patients receiving statin treatment.
The LPA gene encodes apolipoprotein (a), a fatty protein that binds to low-density lipoprotein (LDL), the form of blood cholesterol that is the target of statin drugs. High levels of bound LDL, called Lp(a) for short, is well known to be an independent risk factor for heart disease.
One of the SNPs was highly associated with an increased risk of heart events. When the researchers examined the full EHRs of 11,566 individuals who carried the SNP for more than 1,000 physical conditions, they found significantly higher rates of coronary heart disease and heart attack but not of other diseases.
The approach, called a phenome-wide association study, was pioneered by Denny and his colleagues at Vanderbilt.
“The study highlights the need to consider targeting Lp(a) levels as an important independent factor to reduce cardiovascular risk in patients on statin therapy,” Wei concluded.
Efforts to reduce Lp(a) levels using existing or new drugs could reduce heart events in the proportion of patients on statins who carry LPA variations, he added, although clinical trials would be needed to detect potential side effects and confirm the safety of any such treatment.

Vanderbilt University Medical Centre
news.vanderbilt.edu/2018/05/03/gene-study-spots-clues-to-heart-risk-for-statin-patients/