Researchers have identified the cells that unleash allergy symptoms such as sneezing.

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By Mitch LeslieAug. 2, 2017 , 2:00 PM

If you sneeze your way through ragweed season or need a restraining order against your neighbors cat, researchers finally know what part of your immune system you should blame. A new study nails down the specific group of cells that orchestrates allergic reactions, a result that could help scientists determine not only why some people have allergies, but also how to block them.

Its exciting for those of us who are looking at potential ways to treat allergic diseases, says Thomas Casale, an allergist and immunologist at the University of South Florida in Tampa who wasnt connected to the study.

Allergies stem from mistaken identity, when some of our immune cells respond to benign substancesknown as allergensthat include pollen, mold spores, and certain foods. Researchers know that the culprits that touch off allergic symptoms belong to a group of T cells known as TH2 cells. But not all TH2 cells are culpable. Some guard us against parasites and other invaders. Sorting the beneficial TH2 cells from the rogues has proveddifficult, however.

In the new study, researchers led by T cell biologist Erik Wambre and immunologist William Kwok of the Benaroya Research Institute at Virginia Mason in Seattle, Washington, obtained blood samples from patients who were sensitive to pollen from alder trees, a common cause of winter and spring allergies. An allergic patients TH2 cells recognize and respond to an allergen because they carry receptor, proteins that match allergen molecules. To tag immune cells carrying receptors for alder pollen, the team added customized fluorescent proteins known as MHCII tetramers to the patients blood samples.

Along with receptors, TH2 cells are dotted with marker proteins. Like sports fans wearing their favorite teams jersey, immune cells proclaim their identity with these marker proteins. The researchers analyzed the tagged cells to determine their combination of markers. Compared with other TH2 cells, one group sported more copies of two marker proteins and fewer copies of four others. Although none of the proteins was exclusive to the cells, together they provided a signature for this clique of TH2 cells, which the researchers dubbed TH2A cells. T cells can sometimes shift identifies, but the researchers found that TH2A cells remained distinct, even after several cellular generations. When these cells are born, they are born to be pathogenic, Wambre says.

As they report online today in Science Translational Medicine, Wambre, Kwok, and colleagues found that the cells were abundant in the blood of patients with allergies to a variety of triggers, including grass pollen and house dust mites. But they were absent from the blood of people who werent sensitive. The team also tested patients undergoing an experimental treatment called oral immunotherapy to alleviate their peanut allergies. Over about 20 weeks, the participants receive larger and larger doses of allergy inducing peanut proteins, and this repeated exposure eventually allows them to tolerate peanuts.

We saw a dramatic decrease in TH2A cells after the success of the treatment, Wambre says. The number of these cells in the patients that reacted to peanuts fell by about 90%. Kwok says that the evidence he and his colleagues have accumulated suggests that people with allergies make this specific subset of T cells that probably lead to allergic symptoms.

The work could ultimately benefit patients through new treatments and better ways to monitor the disease, says immunologist Andrew Luster of Massachusetts General Hospital in Charlestown. For example, he notes, scientists could assess trials of oral immunotherapywhich attempts to quell patients allergies with edible doses of food allergensby tracking which treatments were eliminating TH2A cells. Another option, Kwok adds, is that if researchers can determine what molecular signals steer certain T cells to become TH2A cells, they may be able to develop ways to prevent formation of the cells. If researchers succeed in that, they might also prevent a lot of sniffling and scratching.

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Got allergies? Scientists may have finally pinpointed the cells that trigger reactions - Science Magazine

Newswise CHAPEL HILL, NC A team of scientists from the UNC School of Medicine and North Carolina State University (NCSU) has developed promising research towards a possible stem cell treatment for several lung conditions, such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and cystic fibrosis often-fatal conditions that affect tens of millions of Americans.

In the journal Respiratory Research, the scientists demonstrated that they could harvest lung stem cells from people using a relatively non-invasive, doctors-office technique. They were then able to multiply the harvested lung cells in the lab to yield enough cells sufficient for human therapy.

In a second study, published in the journal Stem Cells Translational Medicine, the team showed that in rodents they could use the same type of lung cell to successfully treat a model of IPF a chronic, irreversible, and ultimately fatal disease characterized by a progressive decline in lung function.

The researchers have been in discussions with the FDA and are preparing an application for an initial clinical trial in patients with IPF.

This is the first time anyone has generated potentially therapeutic lung stem cells from minimally invasive biopsy specimens, said co-senior author of both papers Jason Lobo, MD, an assistant professor of medicine at UNC and medical director of lung transplant and interstitial lung disease.

Co-senior author Ke Cheng, PhD, an associate professor in NCSUs Department of Molecular Biomedical Sciences and the UNC/NCSU Joint Department of Biomedical Engineering, said, We think the properties of these cells make them potentially therapeutic for a wide range of lung fibrosis diseases.

These diseases of the lung involve the buildup of fibrous, scar-like tissue, typically due to chronic lung inflammation. As this fibrous tissue replaces working lung tissue, the lungs become less able to transfer oxygen to the blood. Patients ultimately are at risk of early death from respiratory failure. In the case of IPF, which has been linked to smoking, most patients live for fewer than five years after diagnosis.

The two FDA-approved drug treatments for IPF reduce symptoms but do not stop the underlying disease process. The only effective treatment is a lung transplant, which carries a high mortality risk and involves the long-term use of immunosuppressive drugs.

Scientists have been studying the alternative possibility of using stem cells to treat IPF and other lung fibrosis diseases. Stem cells are immature cells that can proliferate and turn into adult cells in order to, for example, repair injuries. Some types of stem cells have anti-inflammatory and anti-fibrosis properties that make them particularly attractive as potential treatments for fibrosis diseases.

Cheng and Lobo have focused on a set of stem cells and support cells that reside in the lungs and can be reliably cultured from biopsied lung tissue. The cells are called lung spheroid cells for the distinctive sphere-like structures they form in culture. As the scientists reported in an initial paper in 2015, lung spheroid cells showed powerful regenerative properties when applied to a mouse model of lung fibrosis. In their therapeutic activity, these cells also outperformed other non-lung-derived stem cells known as mesenchymal stem cells, which are also under investigation to treat fibrosis.

In the first of the two new studies, Lobo and his team showed that they could obtain lung spheroid cells from human lung disease patients with a relatively non-invasive procedure called a transbronchial biopsy.

We snip tiny, seed-sized samples of airway tissue using a bronchoscope, Lobo said. This method involves far less risk to the patient than does a standard, chest-penetrating surgical biopsy of lung tissue.

Cheng and his colleagues cultured lung spheroid cells from these tiny tissue samples until they were numerous enough in the tens of millions to be delivered therapeutically. When they infused the cells intravenously into mice, they found that most of the cells gathered in the animals lungs.

These cells are from the lung, and so in a sense theyre happiest, so to speak, living and working in the lung, Cheng said.

In the second study, the researchers first induced a lung fibrosis condition in rats. The condition closely resembled human IPF. Then the researchers injected the new cultured spheroid cells into one group of rats. Upon studying this group of animals and another group treated with a placebo, the researchers saw healthier overall lung cells and significantly less lung inflammation and fibrosis in the rats treated with lung spheroid cells.

Also, the treatment was safe and effective whether the lung spheroid cells were derived from the recipients own lungs or from the lungs of an unrelated strain of rats, Lobo said. In other words, even if the donated stem cells were foreign, they did not provoke a harmful immune reaction in the recipient animals, as transplanted tissue normally does.

Lobo and Chen expect that when used therapeutically in humans, lung spheroid cells initially would be derived from the patient to minimize any immune-rejection risk. Ultimately, however, to obtain enough cells for widespread clinical use, doctors might harvest them from healthy volunteers, as well as from whole lungs obtained from organ donation networks. The stem cells could later be used in patients as-is or matched immunologically to recipients in much the same way transplanted organs are typically matched.

Our vision is that we will eventually set up a universal cell donor bank, Cheng said.

Cheng, Lobo, and their teams are now planning an initial study of therapeutic lung spheroid cells in a small group of IPF patients and expect to apply later this year for FDA approval of the study. In the long run, the scientists hope their lung stem cell therapy will also help patients with other lung fibrosis conditions of which there are dozens, including COPD, cystic fibrosis, and fibro-cavernous pulmonary tuberculosis.

The lead authors of the two papers were Phuong-Uyen C. Dinh and Jhon Cores, both graduate research assistants in Chengs laboratory.

The National Institutes of Health, the UNC General Assembly Research Opportunities Initiative, and the NC State Chancellors Innovation Fund funded this research.

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Scientists Create Stem Cell Therapy for Lung Fibrosis Conditions - Newswise (press release)

In a groundbreaking experiment, an international team of scientists on Wednesday officially reported the successful elimination of a genetic disease from human embryos.

Its potentially a huge step for medicine -- but also a controversial one. While these embryos, which a team led by researchers at the Oregon Health and Science University edited using a novel gene-editing procedure known as CRISPR-Cas9, were destroyed rather than implanted into a womb, some say this type of genetic manipulation opens the door to other possibilities in human engineering.

Below are answers to some of the common questions about this research.

In short, this experiment showed that it is potentially possible to correct a genetic disease in an embryo with a high chance of success. In order to show this, the researchers created human embryos designed to have a specific genetic mutation responsible for a type of heart disease known as hypertrophic cardiomyopathy. This genetic disease, which occurs in one out of 500 people, can cause sudden death, as well as a host of other cardiac problems such as heart failure and arrhythmias.

Using a technique known as CRISPR-Cas9, the scientists were able to target the faulty genes as the cells in the embryo divided -- swapping them out for a properly functioning form of the gene. What was novel about this study is that researchers were able to nudge the embryo to use its own native machinery to perform the repair with a high degree of efficiency using a correct form of the gene already present in the cell. In this particular experiment, the researchers used CRISPR-Cas9 on 58 embryos containing the mutation. After the procedure, they found that the mutation was corrected in 42 embryos -- a success rate of 72 percent.

If a feat similar to that seen in this experiment could be achieved in an afflicted embryo that was allowed to develop into a person, it would prevent the condition in this individual -- and it would also prevent their future sons and daughters from inheriting this condition well.

Moreover, there are thousands of genetic diseases, ranging from cystic fibrosis to sickle cell anemia, for which such a procedure could be relevant. Tests currently exist to diagnose many diseases prior to birth; however, at this time there is no therapy in use that actually alters the DNA of embryos prior to birth. Of course, the use of such a technique would inevitably raise the prospect of exerting all kinds of control over human reproduction -- as well as a host of new ethical questions.

Its not likely, at least for now. Currently, the U.S. Food and Drug Administration is barred from reviewing investigational medical studies involving editing of human embryos -- something which would be required in order to proceed with moving this research into practice. Additionally, the National Institutes of Health, which is an important source of science research funding in the United States, will not financially support research on gene editing of embryos. The research in this study was not supported by funding from the National Institutes of Health.

Right now, it is unclear. Importantly, even though this experiment was considered to be successful, it is not known how this method would perform in other cases -- for example, a case in which both copies of the gene were mutated rather than just one, which was the case in this experiment. Also, since the scientists destroyed these embryos at a very early stage of development, it is not possible to tell for sure how viable these embryos would actually have been in the long run, or whether there would have been any unforeseen complications with their development.

But along with these scientific questions are also big ethical questions -- ones that will only be answered as scientists, ethicists and the public reflect further on this groundbreaking step.

Will Garneau, M.D., is an internal medicine resident at the Johns Hopkins Hospital.

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Groundbreaking study demonstrates promise and controversy of gene editing in embryos - ABC News

For instance, according to a recent study published by JAMA Oncology, genetic profiling can predict which women with early-stage breast cancer have a lower risk for their cancer coming back after surgery, allowing up to 15 percent of patients to avoid unnecessary chemotherapy.

Most importantly, precision medicines can help patients live longer, healthier lives. Already, the first wave of precision medicines have entered mainstream clinical practice, including targeted therapies that now make it possible for patients with a once incurable form of leukemia, chronic myelogenous leukemia, to live close-to-normal life spans. Similarly, precision medicines are dramatically changing the treatment landscape for deadly cancers like non-small cell lung cancer and metastatic melanoma, not only increasing survival rates but also reducing the need for the costly procedures and hospitalizations that are now part of the standard of care for these diseases.

As a case study, consider acute myeloid leukemia (AML), one of the most serious and challenging blood cancers. Progress understanding and developing effective and safe therapy for patients with AML has been modest, and overall survival for patients with this terrible disease is measured in months. According to a study published by the journal, Biology of Blood and Marrow Transplantation, the average cost for the chemotherapy and stem cell transplantation involved in treating many patients with AML has been estimated to be between $280,000 and $500,000. Discovering why this disease occurs and developing targeted medicines to treat it are really the only alternatives to help these patients and to reduce the cost of treatment failures.

Yet, to realize the promise of precision medicines, we must act collectively across the health-care ecosystem to ensure that patients who desperately need these transformational therapies have access to them.

A problem that too many Americans face when prescribed specialty medicines to treat complex or rare conditions is high out-of-pocket costs. Many patients with the most serious illnesses face high deductibles and coinsurance requirements, which often put the latest, safest and most-effective treatments out of their reach. These patient cost-sharing barriers are one of the reasons half of the medicines used to treat chronic diseases are not taken as prescribed, contributing to the estimated $100 billion to $290 billion of unnecessary costs to the U.S. health-care system from medication non-adherence, as cited by the Annals of Internal Medicine and the New England Journal of Medicine.

We must do better. We need to work together to ensure access to these medicines and reduce the financial burden on patients. Towards this end, Celgene is proactively working with major commercial U.S. health-care payers on arrangements designed to give eligible patients access to our most recently approved medicine a precision therapy with an accompanying diagnostic test without deductibles, co-pays and co-insurance. By partnering with payers to offset and even eliminate patient cost-sharing as an obstacle to treatment, our hope is to prevent some of the financial burden that leads to many of the problems currently impacting patient care.

Our action is just one step in what will be needed to ensure access to the medicines Americans grappling with devastating diseases need. As health-care stakeholders, it is up to all of us to work together to develop market-based solutions to ensure that medical innovation continues to be valued, and that patients have affordable health care. We're not there yet, but we are getting closer. Celgene is working with U.S. commercial health-care payers to step up to that challenge. We are also committed to engaging with policy-makers on finding ways to develop innovative contracting strategies that can benefit patients with government insurance as well. We encourage others in the health-care ecosystem to join us in finding solutions to these challenges.

Commentary by Mark Alles, CEO of Celgene.

For more insight from CNBC contributors, follow @CNBCopinion on Twitter.

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Getting patients access to 'precision' medicines is crucial - CNBC