The numbers are alarming: According to estimates by the World Health Organization (WHO), around six million people die every year from sepsis. The disease, popularly called "blood poisoning", normally starts with a harmless infection.
If this triggers an excessive reaction of the immune system, the body’s own tissue can be attacked and damaged. The overreaction eventually leads to a life-threatening collapse of the body’s defenses. In Germany alone, more people die of sepsis than of AIDS, colon cancer and breast cancer combined.
Researchers around the world are on the search for new therapies – so far in vain. An interdisciplinary team from the fields of structural biology, immunology and cell biology has now, for the first time, successfully produced a protein that could balance the overshooting immune response.
In their work, the scientists were inspired by evolution: mice are well protected from sepsis by their immune systems. Here, interleukins – messengers, that mediate communication between the cells of the immune system – play a key role.
"The interleukins are the vocabulary with which immune cells communicate," explains Matthias Feige, Professor of Cellular Protein Biochemistry at the Technical University of Munich. The cells form these messenger molecules according to a very specific blueprint of individual amino acids. Their arrangement determines, which three-dimensional structure an interleukin adopts and, consequently, which information it transmits.
Humans and mice have similar, yet different vocabularies. The researchers discovered one striking difference in interleukin-27-alpha. This molecule can be released by cells of the mouse immune system – but not by human cells – and regulates immune cell function.
"Using computer models and cell biological experiments, we discovered that a single structurally important amino acid defines whether interleukin-27-alpha is released by cells of the immune system," explains Stephanie Müller, the first author of the study. "That gave us an idea about how we can engineer novel human interleukin proteins that are released by cells so that we can produce them biotechnologically."
The team then prepared the modified interleukin in the laboratory and tested its biological functions – with very encouraging results: The engineered messenger molecule is recognized by human cells. First analyses suggest that it can indeed balance an overreaction of the immune system, making it a promising candidate for sepsis therapy.
"Our approach allowed us to rationally extend the language of immune cells by engineering a key signaling molecule. This provides us with an opportunity to modulate the reaction of immune cells in a targeted manner. Such a finding was only possible thanks to the close collaboration with immunologists and clinicians from TUM, the Université Sorbonne in Paris and the Helmholtz Zentrum Muenchen," says Feige. A patent for the new protein is already pending.
 https://www.tum.de/nc/en/about-tum/news/press-releases/detail/article/35210/

On January 17 global networks and key stakeholders discussed ECRAID and its sustainable solutions to protect Europe from antimicrobial resistance and emerging threats. Kicked off on January 17th 2019 with a high-level meeting in Brussels, PREPARE and COMBACTE have commenced the development of the business plan for ECRAID, the European Clinical Research Alliance on Infectious Diseases. ECRAID envisages a European-wide sustainable clinical research organization for infectious diseases and antimicrobial resistance that stems from both PREPARE and COMBACTE. The Kick-off Meeting opened with prominent speakers such as Marc Bonten, Coordinator of COMBACTE; Herman Goossens, Coordinator of PREPARE; Carlos Moedas, the EU Commissioner for Research, Science and Innovation; Jeremy Farrar, Director of Wellcome Trust; and Magda Chlebus, Executive Director, Science Policy & Regulatory Affairs, EFPIA. In addition, there were panel discussions with the participation of clinical research networks, such as African EDCTP-funded and Latin-America EU-funded organizations, preclinical research networks, SMEs, and pharmaceutical and diagnostic companies. ECRAID’s vision is to establish a coordinated and permanent European clinical research infrastructure for clinical research on infectious diseases. Due to their network, which is built on the foundations laid by COMBACTE (>950 clinical care sites) and PREPARE (primary care sites), ECRAID will be able to conduct clinical research faster and easier. Moreover, ECRAID will have rapid access to and knowledge of well-developed clinical and laboratory sites. Trials will be conducted continuously, allowing them to expand their experience and knowledge. ECRAID aims to protect public health by generating rigorous evidence to improve diagnosis, prevention, and treatment.  The mission is to cultivate world-class research to protect citizens of Europe against antimicrobial resistance and infectious diseases over the long-term.

Researchers at Okayama University report in the journal Arthritis & Rheumatology that monitoring a particular antigen can be used for predicting relapse of the vascular disease AAV.
Antibodies are molecules produced by a human’s immune system to counteract bacteria and viruses. When a bacterial or viral pathogenic molecule (a so-called antigen) is detected, an antibody neutralizes it by binding to it. However, autoantibodies are sometimes produced against our own protein and cause autoimmune diseases.  For the autoantibody known as ANCA (antineutrophil cytoplasmic antibody) cause ANCA-associated vasculitis (AAV), at least two antigens exist: proteinase 3 and myeloperoxidase (abbreviated as PR3 and MPO, respectively).
Assistant Professor Haruki Watanabe and Associate Professor Ken-Ei Sada from Okayama University and colleagues have now investigated whether MPO-ANCA can be used as a biomarker for the relapse of AAV, a blood-vessel inflammation disease. The researchers’ findings suggest that monitoring MPO-ANCA is useful for predicting relapse in patients with AAV.
The scientists looked at data for 271 MPO-ANCA-positive patients who had achieved remission (disappearance of the signs and symptoms) of AAV during 6 months after therapy was started. Levels of MPO-ANCA were measured at several times in a 2-year period.  Assistant Professor Haruki Watanabe and Associate Professor Ken-Ei Sada from Okayama University and colleagues found that for 72% of the patients, MPO-ANCA levels decreased to normal within 6 months after therapy began. MPO-ANCA reappeared for 40% of the patients for which there were complete follow-up data; this reappearance was associated with a relapse occurring simultaneously or later. The researchers therefore concluded that reappearance of MPO-ANCA is a promising marker for AAV relapse.
Assistant Professor Haruki Watanabe and Associate Professor Ken-Ei Sada from Okayama University and colleagues found indications that MPO-ANCA reappearance could be particularly useful as a biomarker for relapse of AAV with kidney involvement (renal AAV).  Since only 4 patients without renal involvement experienced relapse, a larger study would be necessary to establish any link between MPO-ANCA reappearance and relapse of non-renal AAV.
The researchers point out that their study has some limitations: the data were obtained earlier, in the context of other investigations, and different participating institutions used different analytic procedures for qualitatively assessing ANCA content. Nevertheless, the study was the largest so far, and also the first with case–control analysis (based on comparisons of patients with and without the disease relapse).  Watanabe and colleagues conclude that for patients recovered from MPO-AAV, “routine MPO-ANCA monitoring should be implemented [to predict possible relapse]”.

Tel Aviv University researchers have developed a new blood test for genetic disorders that may allow parents to learn about the health of their baby as early as 11 weeks into pregnancy.
The simple blood test lets doctors diagnose genetic disorders in fetuses early in pregnancy by sequencing small amounts of DNA in the mother’s and the father’s blood. A computer algorithm harnessing the results of the sequencing would then produce a “map” of the fetal genome, predicting mutations with 99% or better accuracy depending on the mutation type.
Prof. Noam Shomron of TAU’s Sackler School of Medicine led the research.
“Non-invasive prenatal tests are already available for chromosome disorders such as Down syndrome,” Prof. Shomron says. “Our new procedure is based on fetal DNA fragments that circulate freely in maternal blood and bears only a minimal risk for the mother and fetus compared with such invasive techniques as the amniotic fluid test. We will now be able to identify numerous mutations and diseases in a safe and simple procedure available at the doctor’s office.
“The genetic mechanism behind Down syndrome affects a very large portion of the genome and therefore is easier to detect,” Prof. Shomron explains. “We performed upgraded non-invasive fetal genotyping, using a novel approach and an improved algorithm, to detect many other diseases that are caused by smaller parts of the genome. This is like looking at a map of the world and noticing not only that a continent is missing, but also that a single house is missing.
“The practical applications are endless: a single blood test that would detect a wide range of genetic diseases, such as Tay-Sachs disease, cystic fibrosis and many others.”
Prof. Shomron and colleagues tested blood samples from three families at Rabin Medical Center in the 11th week of gestation. They extracted maternal and paternal DNA from their white blood cells and fetal DNA from a placental cell sample. They also extracted circulating cell-free fetal DNA from the maternal blood.
“We sequenced all these DNA samples and created a computer algorithm that utilizes the parental DNA as well as the cell-free fetal DNA to reconstruct the fetal genome and predict mutations,” says Prof. Shomron. “We compared our predictions to the true fetal DNA originating from the placenta. Our model is the first to predict small inherited insertions and deletions. The method described can serve as a general framework for non-invasive prenatal diagnoses.”

American Friends of Tel Aviv Universityhttps://tinyurl.com/y43kk6sx

Hologic announced recently that its Aptima® HIV-1 Quant Dx Assay has received two new CE marks in Europe – for early infant diagnosis (EID) and for testing dried blood spots (DBS).  This means the assay can be used to qualitatively detect HIV-1 RNA as an aid in the diagnosis of HIV-1 infected infants under 18 months old, and to test an additional sample type (DBS) to monitor viral load and disease progression in HIV-1 infected individuals in European and African countries. It is the first and only dual-claim assay for both viral load and early infant diagnosis. The dried blood spot claim is particularly important in the African market as it is a much more stable and easily transportable sample type than liquid blood.
The Aptima HIV-1 Quant Dx assay is an in vitro nucleic acid amplification test (NAAT) for the detection and quantitation of HIV type 1 (HIV-1) on the fully automated Panther™ system. It is intended as an aid in the diagnosis of HIV-1 infection, as a confirmation of HIV-1 infection, and as an aid in the clinical management of patients infected with HIV-1. The Aptima HIV-1 Quant Dx assay may also be used in conjunction with clinical presentation and other laboratory markers for disease prognosis in HIV-1 infected individuals.  
“With 25 million people infected with HIV in sub-Saharan Africa alone, there continues to be an urgent need for accessible testing, which is crucial for managing care and reducing the spread of this life-threatening infection,” said João Malagueira, vice president, Europe South and Indirect Markets. “These new product extensions, along with the recent announcement of our Hologic Global Access Initiative, underline Hologic’s commitment to providing accessible testing.  They will enable healthcare providers in resource-limited settings to scale up their HIV testing programmes to meet the 95-95-95 goals set out by the World Health Organization (WHO).”
The Aptima HIV-1 Quant Dx assay was awarded World Health Organization prequalification for in vitro diagnostics using plasma samples on December 21, 2017. This means that the assay meets WHO standards of quality, safety, performance and reliability, and allows global health organizations to consider the Aptima HIV-1 Quant Dx assay for public sector procurement in resource-limited settings.
The Aptima HIV-1 Quant Dx assay is processed on Hologic’s Panther system, an integrated platform that fully automates molecular testing with true sample-to-result automation, adaptable workflow options, and a broad testing menu. The Panther system is designed to be modular and scalable, accommodating the needs of large, centralized labs as well as smaller, decentralized labs. The Panther system offers the highest throughput per square meter of any comparable molecular diagnostic instrument – up to 320 results in 8 hours in less than one square meter of space.
www.hologic.com