Analysis: Quicker Autoimmune-Disorder Rx

By ASTARA MARCH

A new discovery might mean patients with autoimmune diseases can be treated with a quick shot in a doctor’s office, instead of enduring the current, cumbersome process of going to the hospital for a three-hour infusion, say U.S. and international researchers.

A team at Cornell Weill Medical Center in New York City say they have found a way to isolate the active ingredient in the intravenous immune globulin (IVIG) used to treat autoimmune diseases like multiple sclerosis and lupus. That active ingredient blocks the function of interferon gamma, a major culprit in the chronic inflammation seen in these diseases.

Thus, this tiny portion — 0.5 percent — of the IVIG solution that actually does the work can be reduced to a simple injection, the researchers said.

If this becomes available and is as effective as the full intravenous treatment, it would be very helpful to patients: more convenient, less expensive, and safer, Virginia Ladd, president of the American Autoimmune and Related Diseases Association, told United Press International.

If the discovery can be translated to medical practice, the resulting simplified treatment would be easier for patients and also safer, the researchers said.

The standard IVIG treatment is made by harvesting gamma globulin from thousands of blood samples. The risk of contamination by dangerous organisms, such as HIV or hepatitis C, is high, and sometimes whole batches are recalled because of this problem.

In addition, when there is a shortage in blood donations, there is a shortage of IVIG as well, and people with immunodeficiency diseases, whose life is dependent on IVIG, can be in serious trouble, the researchers noted.

IVIG is also time-consuming and expensive to make and administer.

People with autoimmune problems must come to the hospital for three to four hours a day on three consecutive days to receive enough IVIG to have an effect on their disorder. They can have allergic reactions to the product and the sheer amount of fluid they must receive can overload their kidneys.

We may be able to eliminate many of these problems, Lionel Ivashkiv, rheumatologist and director of Basic Research at the Hospital for Special Surgery/Cornell Weill Medical Center in New York, N.Y., told United Press International. Our study showed us that we can make the immune complexes that are the active component of IVIG in the laboratory using antibody/antigen systems that are commonplace and innocuous. Doing so would eliminate all the risks of contamination associated with human blood products and the problems associated with intravenous infusions, because they could be given in a single injection in a doctor’s office.

However, Ivashkiv cautioned that the new approach appears limited to use in people with autoimmune diseases. People with immune deficiencies will still be dependent on IVIG, he said.

Ivashkiv and his colleagues happened upon the discovery while trying to find a way to block the inflammatory factors responsible for autoimmune disorders, such as multiple sclerosis, lupus erythematosus, Kawasaki disease, and chronic lymphocytic leukemia, so they decided to study how IVIG works in more detail.

They and others had discovered that IVIG attaches to a receptor on the outside of cells called FcyRllb and stops it from activating inflammatory factors. The team wondered if interferon gamma, which is found in high amounts in many chronic autoimmune diseases, was one of the factors IVIG impacts. To find out, they treated mouse and human white blood cells called macrophages with IVIG. Macrophages are scavenger cells that use interferon gamma to kill invading bacteria, but when treated with IVIG, they couldn’t do so.

The next step was to see what part of IVIG was actually doing the work. IVIG is comprised of 99.5 percent gamma globulin and 0.5 percent immune complexes. When macrophages were treated with gamma globulin alone, their performance was not affected, but when they were cultured with immune complexes, the macrophages were again stopped in their tracks.

When asked how soon patients could benefit from the experimental treatment, Ivashkiv said he thought the discovery might be able to get to the bedside in little more than three years.

That is because the researchers have already tested the therapy on human cells with no adverse effects, the components of the treatment have been in use for many years and are already approved in the United States and abroad, and because other researchers are also working on the same problem, he noted.

Our coalition involved scientists here in the United States, Canada, and Australia, said Ivashkiv, plus there is a Canadian group led by Vinayakimar Siragam and Alan Lazarus who are working on a similar immune complex preparation to treat immune thrombocytopenic purpura (ITP), which causes low platelet counts. We are happy about their work, because it uses a different mechanism than ours, so it will work better for different problems.

Ivashkiv said that, since there were no safety or toxicity issues with the new treatment, human clinical trials could begin in the very near future.

Really, there are no barriers to human testing, (except for) deciding on the kind of immune complex that should be used, said Ivashkiv. As soon as we find a partner with experience developing pharmaceutical products to help us do this, we can begin.