Glaucoma, a disease that afflicts nearly 70 million people worldwide, is something of a mystery despite its prevalence. Little is known about the origins of the disease, which damages the retina and optic nerve and can lead to blindness.
A new study from MIT and Massachusetts Eye and Ear has found that glaucoma may in fact be an autoimmune disorder. In a study of mice, the researchers showed that the body’s own T cells are responsible for the progressive retinal degeneration seen in glaucoma. Furthermore, these T cells appear to be primed to attack retinal neurons as the result of previous interactions with bacteria that normally live in our body.
The discovery suggests that it could be possible to develop new treatments for glaucoma by blocking this autoimmune activity, the researchers say.
“This opens a new approach to prevent and treat glaucoma,” says Jianzhu Chen, an MIT professor of biology, a member of MIT’s Koch Institute for Integrative Cancer Research, and one of the senior authors of the study.
Dong Feng Chen, an associate professor of ophthalmology at Harvard Medical School and the Schepens Eye Research Institute of Massachusetts Eye and Ear, is also a senior author of the study. The paper’s lead authors are Massachusetts Eye and Ear researchers Huihui Chen, Kin-Sang Cho, and T.H. Khanh Vu.
One of the biggest risk factors for glaucoma is elevated pressure in the eye, which often occurs as people age and the ducts that allow fluid to drain from the eye become blocked. The disease often goes undetected at first; patients may not realize they have the disease until half of their retinal ganglion cells have been lost.
Most treatments focus on lowering pressure in the eye (also known as intraocular pressure). However, in many patients, the disease worsens even after intraocular pressure returns to normal. In studies in mice, Dong Feng Chen found the same effect.
“That led us to the thought that this pressure change must be triggering something progressive, and the first thing that came to mind is that it has to be an immune response,” she says.
To test that hypothesis, the researchers looked for immune cells in the retinas of these mice and found that indeed, T cells were there. This is unusual because T cells are normally blocked from entering the retina, by a tight layer of cells called the blood-retina barrier, to suppress inflammation of the eye. The researchers found that when intraocular pressure goes up, T cells are somehow able to get through this barrier and into the retina.
The Mass Eye and Ear team then enlisted Jianzhu Chen, an immunologist, to further investigate what role these T cells might be playing in glaucoma. The researchers generated high intraocular pressure in mice that lack T cells and found that while this pressure induced only a small amount of damage to the retina, the disease did not progress any further after eye pressure returned to normal.
Further studies revealed that the glaucoma-linked T cells target proteins called heat shock proteins, which help cells respond to stress or injury. Normally, T cells should not target proteins produced by the host, but the researchers suspected that these T cells had been previously exposed to bacterial heat shock proteins. Because heat shock proteins from different species are very similar, the resulting T cells can cross-react with mouse and human heat shock proteins.
To test this hypothesis, the team brought in James Fox, a professor in MIT’s Department of Biological Engineering and Division of Comparative Medicine, whose team maintains mice with no bacteria. The researchers found that when they tried to induce glaucoma in these germ-free mice, the mice did not develop the disease.
The researchers then turned to human patients with glaucoma and found that these patients had five times the normal level of T cells specific to heat shock proteins, suggesting that the same phenomenon may also contribute to the disease in humans. The researchers’ studies thus far suggest that the effect is not specific to a particular strain of bacteria; rather, exposure to a combination of bacteria can generate T cells that target heat shock proteins.
One question the researchers plan to study further is whether other components of the immune system may be involved in the autoimmune process that gives rise to glaucoma. They are also investigating the possibility that this phenomenon may underlie other neurodegenerative disorders, and looking for ways to treat such disorders by blocking the autoimmune response.
“What we learn from the eye can be applied to the brain diseases, and may eventually help develop new methods of treatment and diagnosis,” Dong Feng Chen says.

MITnews.mit.edu/2018/glaucoma-autoimmune-disease-0810

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.