In severe cases of COVID-19, Emory researchers have been observing an exuberant activation of B cells, resembling acute flares in systemic lupus erythematosus (SLE), an autoimmune disease.
The findings point towards tests that could separate some COVID-19 patients who need immune-calming therapies from others who may not. It also may begin to explain why some people infected with SARS-CoV-2 produce abundant antibodies against the virus, yet experience poor outcomes.
The results were published online on Oct. Read more
Emory rheumatologist Arezou Khosroshahi was the lead author on a differential diagnosisÂ case report in New England Journal of MedicineÂ published in October, which describesÂ an example of IgG4-related disease. This autoimmune conditionâ€™s name was agreed upon only recently, at an international conference she co-directed in 2011.
This review calls IgG4-related disease an â€œorphan disease with many faces.â€Â It sounds like each case has the potential to be an episode of House. As Khosroshahi explains:
â€œMost patients undergo invasive procedures for resection or biopsy of the affected organ to exclude other conditions. Unfortunately, most of those patients get dismissed by the clinicians, given the good news that their disease was not malignancy. Many of them have recurrence of the condition in other organs after a few months or years.â€
Rheumatologist Arezou Khosroshahi, MD
In the case report, a woman was admitted to Massachusetts General Hospital, because of shoulder and abdominal pain and an accumulation of fluid around her lungs. Surgeons removed a softball-sized mass from her right lung. The mass did not appear to be cancerous, but instead seemed to be the result of some kind of fibrous inflammation, and the patientÂ was treated with antibiotics. Read more
A common cause of bone loss is an overactive parathyroid gland, which doctors usually treat with surgery. New research on how excess parathyroid hormone affects immune cells suggests that doctors could repurpose existing drugs to treat hyperparathyroidism without surgery.
The results were publishedÂ October 8 inÂ Cell Metabolism. [My apologies for not posting thisÂ in October.]
“Surgery is sometimes not an appropriate remedy for hyperparathyroidism because of the condition of the patient, and it is also expensive,” says lead author Roberto Pacifici, MD. “Also, the one pharmacological treatment that is available, cinacalcet, is not always the ideal solution. This work could potentially lead to alternatives.”
Roberto Pacifici, MD
Researchers at Emory University School of Medicine led by Pacifici teamed up with doctors from the University of Turin in Italy, combining observations of human patients with an overactive parathyroid with experiments on mice.
The drugs identified as potential treatments are: calcium channel blockers, now used to treat high blood pressure, and antibodies that block the inflammatory molecule IL-17A, under development for the skin disease psoriasis. Clinical trials would be necessary to show that these drugs are effective against parathyroid hormone-induced bone loss in humans. Read more
I was struck by one part of Mirko Paiardini’s paper that was published this week in Journal of Clinical Investigation. It describes aÂ treatment aimed at repairing immune function in SIV-infected monkeys, with an eye toward helping people with HIV one day.Â One of the goals of their IL-21 treatment is to restoreÂ intestinal Th17 cells, which are depleted by viral infection.Â In this context, IL-21’s effect is anti-inflammatory.
However, Th17 cells are also involved in autoimmune disease. A recent Cell Metabolism paper from endocrinologist Roberto Pacifici and colleagues examinesÂ Th17 cells, with the goal of treating bone loss coming from an overactive parathyroid. In that situation, too many Th17 cells are bad and they need to be beaten back. Fortunately, bothÂ an inexpensive blood pressure medication and a drugÂ under development for psoriasisÂ seem to do just that.
Emory immunologistsÂ have identified corresponding cells in which long-lived antibody production resides. A subset of plasma cells keep a catalog of how an adultâ€™s immune system responded to infections decades ago, in childhood encounters with measles or mumps viruses.
The results, published Tuesday, July 14 inÂ Immunity, could provide vaccine designers with a goalpost when aiming for long-lasting antibody production.
â€œIf youâ€™re developing a vaccine, you want to fill up this compartment with cells that respond to your target antigen,â€ says co-senior author F. Eun-Hyung Lee, MD, assistant professor of medicine at Emory University School of Medicine and director of Emory Healthcareâ€™s Asthma, Allergy and Immunology program.
The findings could advance investigation of autoimmune diseases such as lupus erythematosus or rheumatoid arthritis, by better defining the cells that produce auto-reactive antibodies.
Lee says that her team’s research on plasma cells in humansÂ provided insights unavailable from mice, since mice don’t live as long and their plasma cellsÂ also have a different patternÂ of protein markers.Â More here.
Can it really be possible to transform a person’s own cells into a weapon against various forms of disease? And what if those very cells could be retrained to attack cancer cells or to prevent autoimmune diseases?
Answers to these questions and many more are about to soon be realized, as Emory University Hospital will serve as the launch site for the very appropriately-named EPIC (Emory Personalized Immunotherapy Center).
The new Center, which is the creation of Dr. Jacques Galipeau, MD, professor of hematology and medical oncology & pediatrics of Emory University, will soon be operational after final touches have been put on construction of the lab. This cell processing facility will foster development of novel personalized cellular therapies for Emory patients facing catastrophic ailments and unmet medical needs.
According to Galipeau, the premise of EPIC and its overlying mission will focus on cellular and biological therapies that use a patientâ€™s own cells as a weapon to seek and destroy cells that actually make a person sick. In partnership with the Winship Cancer Institute of Emory University, Childrenâ€™s Healthcare of Atlanta, Aflac Cancer & Blood Disorders Center and the Emory School of Medicine, EPIC seeks to improve the health of children and adults afflicted with cancer and immune disease.
â€œFirst and foremost, we seek to bring a level of care and discovery that is first in Georgia, first in human and first in child. Blood and marrow derived cells have been used for more than a quarter century to treat life threatening hematological conditions and are now established therapies worldwide. More recently, the use of specific adult somatic cells from marrow, blood and other tissues are being studied in cellular medicine of a wide array of ailments including heart, lung, neurological and immune diseases,â€ says Galipeau. â€œThe use of blood borne immune cells can also be exploited for treatment of cancer, autoimmune disease, organ transplantation and chronic viral illnesses such as HIV.â€
Galipeau said that once operational, EPIC willÂ begin by working with Crohnâ€™s disease in pediatric and adult patients, an inflammatory bowel disease. Symptoms of Crohnâ€™s disease include severe abdominal pain, diarrhea, fever, weight loss, and the inability for a child to properly grow. Resulting bouts of inflammation may also affect the entire digestive tract, including the mouth, esophagus and stomach.Â In some cases, a radical surgery involving the removal of part of the lower intestinal tract is required.
â€œThere is no current answer for what specifically causes Crohnâ€™s disease, nor is there a cure. But we hope that through our research and efforts, we will be able to first target the inflammatory mechanisms in these patients through immunotherapy, and in turn reduce the amount of flare-ups and limitÂ the damage that occurs from this disease,â€ says Galipeau.
Galipeau says the EPIC program could represent a powerful cornerstone to the launch and the development of an entirely new, Emory-based initiative which bundles the strengths of the School of Medicine, Emory University Hospital, Children’s Healthcare of Atlanta, and many Woodruff Health Sciences Center centers of excellence,â€ says Galipeau.
â€œMy ultimate goal is to elevate the biomedical scientific and scholarly enterprise to aÂ higher level – making a difference in the lives of people. The EPIC program and multi-levels of support could be a fundamental underpinning to our success.â€
B cells are workhorses of the immune system. Their main function is to produce antibodies against bacteria or viruses when they encounter something that they recognize.Â But recently researchers have been getting hints that certain kinds of B cells can also have a calming effect on the immune system. This property could come in handy with hard-to-treat conditions such as graft-vs-host disease, multiple sclerosis, or Crohn’s disease.
Hematologist Jacques Galipeau has found that B cells treated with an artificial hybrid molecule called GIFT15 turn into “peacemakers”. These specially treated B cells can tamp down the immune system in an experimental animal model of multiple sclerosis, suggesting that they could accomplish a similar task with the human disease.
Galipeau’s paper inÂ Nature Medicine from August 2009 says succinctly: “We propose that autologous GIFT15 B regulatory cells may serve as a new treatment for autoimmune ailments.”Â Galipeau, a recent arrival to Emory from McGill University in Montreal, explains this tactic and other aspects of personalized cell therapy in the video above. Read more
Today, S. Sam Lim, MD, assistant professor of medicine, Emory School of Medicine, and chief of rheumatology at Grady Memorial Hospital, will host a live chat on the Lupus Foundation of America website to help educate people with lupus about the need to adhere to their medications as prescribed.
S. Sam Lim, MD
Lim heads two lupus clinics and is involved in several federal, state and privately funded projects, including the CDC-funded Georgia Lupus Registry. He also serves on the Medical Scientific Advisory Committee of the Lupus Foundation of America and its Georgia Chapter.
Lupus (systemic lupus erythematosus, or SLE) is a chronic inflammatory disease that can affect various parts of the body, especially the skin, joints, blood, and kidneys. The potentially life-threatening autoimmune disease affects an estimated 1.5 million Americans.
Medications cannot cure lupus, but they play an important role in managing the signs and symptoms of lupus and can often prevent or slow organ damage. Medication treatment for lupus often involves reaching a balance between preventing severe, possibly life-threatening organ damage, maintaining an acceptable quality of life and minimizing side effects.
Because most lupus symptoms are caused by inflammation, nonsteroidal anti-inflammatory drugs (NSAIDs) and antimalarial medications are usually enough to reduce symptoms, says Lim. Medications range in strength from mild to extremely strong, and often several drugs are used in combination to control the disease.
According to a new study published in the journal Arthritis Care and Research, depression is a leading reason why patients with systematic lupus erythematosus (SLE) may not take their medication.
Good communication between people with lupus and their doctors is essential to ensure effective management of the medicines that are prescribed, says Lim. An array of drug therapies is now available, and more than 30 clinical studies are underway of potential new treatments for lupus. Lim recently received a $1 million grant from the Georgia Department of Human Resources to continue his work gathering data for the five-year-old Georgia Lupus Registry, the largest, most comprehensive population-based lupus registry in the country.