Two new studies find potential genetic cause and new treatment method for autoimmune diseases

The American Autoimmune Related Diseases Association, Inc. (AARDA) is spotlighting two new research studies originally reported in ScienceDaily. The first study advances understanding of a potential cause of autoimmune disease, while the second examines a new treatment approach that could have wide-ranging implications for many autoimmune diseases.

In both cases, AARDA believes the research is promising and additional studies are needed to confirm the findings.

Potential Genetic Trigger of ADs Identified

Researchers at the Hospital for Special Surgery (HSS) in New York City, reporting in the June issue of Arthritis and Rheumatism, have found virus-like elements within the human genome that may be a potential genetic trigger of systemic autoimmune disease.

According to ScienceDaily (June 27, 2016):
"For their study, the HSS researchers hypothesized that the abnormal expression of genetic elements known as LINE-1 ( L1) retroelements might trigger an innate immune response similar to that produced by outside viruses and contribute to an overproduction of interferons.

Interferons are molecules our body produces in the presence of viruses and other pathogens to mobilize the immune system. They're part of the complex immune response to combat danger. However, if levels of interferon are too high, instead of playing a protective role it can contribute to the development of autoimmune disease."
The researchers sought to understand why a class of interferon known as type 1 interferon, is excessively produced in patients with SLE and Sjogren's syndrome.

"Our genomes are packed with sequences derived from viruses that were inserted many thousands of years ago, and these virus-like sequences can move around, causing genetic mutations and contributing to the evolution of our genomes. We hypothesized that they sometimes generate virus-like RNA sequences that can be detected by the immune system," said Mary K. Crow, MD, physician-in-chief at Hospital for Special Surgery and senior study author.

"Our findings support the hypothesis that L1 retroelements, perhaps along with other virus-derived genomic elements, may contribute to the development of autoimmune disorders characterized by high levels of type 1 interferon," said Dr. Crow, chair, Department of Medicine, and Benjamin M. Rosen Chair in Immunology and Inflammation Research at HSS. "Although it may not be the only cause, it's intriguing to think that virus-derived elements in our own genome are either quiet and don't cause any trouble, or they get stirred up and contribute to disease."

Commenting on the study, Noel R. Rose, MD, Ph.D., chairman emeritus of AARDA's Scientific Advisory Board, said the findings, "Iook very much like what I have always called the "adjuvant effect". All of us are prone to develop some autoimmunity (self-reactive lymphocytes) depending upon our genetics. But we need an extra push -- the adjuvant to move from benign autoimmunity to autoimmune disease. Often the adjuvant is supplied by infection or the body's response to infection. This study suggests that an interferon-like molecule is the adjuvant."

Promising New AD Treatment in PreClinical Study Reported
A new treatment approach used in a preclinical study may hold promise for a wide array of autoimmune disease. Scientists at the University of Pennsylvania School of Medicine (Penn) have developed "a method for removing the subset of antibody-making cells that produce autoimmune disease without harming the immune system,"

ScienceDaily (June 30, 2016) reports:
"The key element in the new strategy is based on an artificial target-recognizing receptor, called a chimeric antigen receptor, or CAR, which can be engineered into patients' T cells. In human trials, researchers remove some of patients' T cells through a process similar to dialysis and then engineer them in a laboratory to add the gene for the CAR so that the new receptor is expressed in the T cells. The new cells are then multiplied in the lab before re-infusing them into the patient. The T cells use their CAR receptors to bind to molecules on target cells, and the act of binding triggers an internal signal that strongly activates the T cells -- so that they swiftly destroy their targets.

Current therapies for autoimmune disease, such as prednisone and rituximab, suppress large parts of the immune system, leaving patients vulnerable to potentially fatal opportunistic infections and cancers.

The Penn researchers demonstrated their new technique by successfully treating pemphigus vulgaris, an otherwise fatal autoimmune disease, in a mouse model, without apparent off-target effects which could harm healthy tissue. The results are published in an online First Release paper in Science.

"This is a powerful strategy for targeting just autoimmune cells and sparing the good immune cells that protect us from infection," said co-senior author Aimee S. Payne, MD, PhD, the Albert M. Kligman Associate Professor of Dermatology.
Payne and her co-senior author Michael C. Milone, MD, PhD, an assistant professor of Pathology and Laboratory Medicine, adapted the technique from the promising anti-cancer strategy by which T cells are engineered to destroy malignant cells in certain leukemias and lymphomas.

"Our study effectively opens up the application of this anti-cancer technology to the treatment of a much wider range of diseases, including autoimmunity and transplant rejection," Milone said.

AARDA's Rose said of the study, "What a great example of the 'Ying-Yang' synergy between cancer research and research on the autoimmune diseases. Many of the key ideas behind CAR T cells arose from years of fundamental research on autoimmunity. Now a new method of cancer immunotherapy is being applied to treating autoimmune disease.
"You never know where basic research will take you."