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OUR IMMUNE SYSTEM WORKS hard to fight viruses, bacteria and infections. However, in some of us, the immune system doesn't work like it should. When you have an autoimmune disease, it causes your immune cells to attack your body. This can happen anywhere in the body. Autoimmune diseases are more common in women and are thought to be caused by both genetics and environmental factors.


There are more than 80 autoimmune diseases, according to the National Institute of Environmental Health Sciences. In the U.S., autoimmune diseases affect more than 24 million people, the NIEHS reports. Some of the most common autoimmune diseases include:

Autoimmune thyroid disease.
Inflammatory bowel disease.
Lupus (also called systemic lupus erythematosus).
Multiple sclerosis.
Rheumatoid arthritis.
Type 1 diabetes.

https://health.usnews.com/conditions/au ... and-cancer

Researchers have launched a clinical trial to test an immunotherapy drug in patients who have both cancer and an autoimmune disease, such as rheumatoid arthritis, lupus, or multiple sclerosis.

Immunotherapy drugs enhance the ability of the immune system to detect and kill tumor cells. In recent years, these therapies have benefited a growing number of patients, including some patients with advanced cancers.

But doctors have not known whether immunotherapy is safe and effective for people who have both cancer and an autoimmune disease, because such patients have been excluded from clinical trials of immunotherapy drugs.

“Having an overactive immune system is the main reason that many patients with both cancer and autoimmune diseases have not been included in hundreds of clinical trials of immunotherapy drugs,” said Hussein Tawbi, M.D., Ph.D., of the University of Texas MD Anderson Cancer Center and one of the lead investigators for the new trial.

For many doctors who treat patients with both diseases, the lack of information on the effects of immunotherapy in such patients has led to a “clinical conundrum,” Dr. Tawbi continued.

“As doctors, we have been afraid of using these drugs in patients with autoimmune diseases because we don’t have evidence that they are safe for these patients,” he added. “There’s no guidance on how to handle these cases.”

The main concerns, Dr. Tawbi explained, are that “the immune-related side effects may be more severe in patients with both diseases, or that their autoimmune conditions may get much worse because of immunotherapy.”

In addition, because these patients have been excluded from clinical trials, doctors don’t know “whether they may respond better [than other patients]—or possibly worse because they could be on therapy to suppress the immune system,” he added.

The new clinical trial, which is sponsored by NCI, is intended to help researchers understand the potential harms and benefits of using immunotherapy in patients with certain autoimmune diseases.

The trial could also yield insights into the biology of autoimmune diseases, which could help researchers explore new treatments, according to Dr. Tawbi.

“This study is the first of its kind,” he said. “What we learn may allow us to extend the promise of immunotherapy in a safe manner to patients who have cancer and an existing autoimmune disease.”

Between 10% and 30% of cancer patients have an autoimmune disease as well, so the results of the trial could have implications for many patients, said Elad Sharon, M.D., M.P.H., of NCI’s Cancer Therapy Evaluation Program and another leader of the study.

https://www.cancer.gov/news-events/canc ... ical-trial

“Releasing the Brakes” on the Immune System”

“Autoimmune diseases occur when the immune system goes awry and starts to attack the body’s healthy tissues.

Immunotherapy drugs, such as immune checkpoint inhibitors, “release the brakes” on the immune system, allowing immune cells to detect and attack tumor cells.

In some patients, immunotherapy can cause the immune system to recognize some of the body’s healthy tissues as foreign and attack them. This can lead to side effects such as inflammation of the inner lining of the colon, the lungs, or heart muscle.

Some doctors have been concerned that stimulating the immune system against tumors might “unleash the wrath of autoimmunity,” causing potentially severe and even life-threatening complications, Dr. Tawbi noted.

To address such concerns, the new clinical trial will enroll 260 people who have advanced cancer and an autoimmune disease, including dermatomyositis, systemic sclerosis, rheumatoid arthritis, lupus, inflammatory bowel disease, Crohn’s disease, multiple sclerosis, and Sjogren’s syndrome.

Before and after hand x-rays from a woman with rheumatoid arthritis.
X-ray images of the hand of a woman with rheumatoid arthritis (left) and 8 years later (right).
Credit: Mikael Häggström, Creative Commons
Participants will receive nivolumab (Opdivo), an immune checkpoint inhibitor approved by the Food and Drug Administration to treat a number of cancers, including Hodgkin lymphoma and liver, lung, kidney, and bladder cancers.

To determine the safety of the drug in the new trial, the researchers will monitor participants for the sudden emergence of severe autoimmune symptoms, known as flares. The researchers will assess the drug’s effectiveness by tracking patients’ responses to treatment, how long patients survive without their diseases getting worse, and how long patients survive. “

“The Expanding Use of Immunotherapy”

“In recent years, the use of immunotherapy for patients with cancer has been expanding rapidly. Immune checkpoint inhibitors, for example, have been tested in a growing number of cancer types, in combination with other therapies, and in patients with different stages of disease.

These efforts underscore the need to develop scientific evidence to guide decisions about whether to use a rapidly growing class of treatments for patients with autoimmune disease and cancer, according to
Dr. Sharon. “

“If we can learn how to use immunotherapy to treat people with both cancer and autoimmune diseases, then we could offer these patients potentially curative therapy,” he added.”

D.ap wrote: ↑Sat Sep 26, 2020 10:12 am “The Expanding Use of Immunotherapy”

“In recent years, the use of immunotherapy for patients with cancer has been expanding rapidly. Immune checkpoint inhibitors, for example, have been tested in a growing number of cancer types, in combination with other therapies, and in patients with different stages of disease.

These efforts underscore the need to develop scientific evidence to guide decisions about whether to use a rapidly growing class of treatments for patients with autoimmune disease and cancer, according to
Dr. Sharon. “

“If we can learn how to use immunotherapy to treat people with both cancer and autoimmune diseases, then we could offer these patients potentially curative therapy,” he added.”

The bend that breaks the brake


“A single amino acid change puts a bend in a protein that switches off immune cells, releasing the brakes on the immune system.”

https://elifesciences.org/digests/46689 ... -the-brake

The bend that breaks the brake


“A single amino acid change puts a bend in a protein that switches off immune cells, releasing the brakes on the immune system.

Left unchecked the immune system can cause devastating damage to healthy tissue. To prevent this from happening, immune cells have built-in off switches that dampen their activation. One such switch is a protein called FcγRIIB that sits on the outer surface of immune cells and binds to proteins known as antibodies, which are produced as part of the immune response. Its role is to act as a brake on the immune system, and stop it from getting out of control.

Overactive immune cells can lead to autoimmune diseases such as systemic lupus erythematosus, also known as SLE for short, which causes damage to the skin, joints and other organs. Previous work suggests that SLE is correlated with a specific mutation in the FcγRIIB gene, but it is unclear how the mutation and the disease are connected.

Proteins are made out of building blocks called amino acids, which have different chemical properties. A swap of one amino acid for another can have big consequences for the structure of a protein. In the case of FcγRIIB, the mutation that correlates with SLE changes an amino acid called isoleucine for another called threonine. Isoleucine does not mix well with water and is commonly found buried in the middle of proteins or inside cell membranes. Threonine, on the other hand, can readily interact with the hydrogen atoms in water and other amino acids.”