IFNa-kinoid shows promise against lupus

The first study to show results using active immunotherapy against the signaling protein interferon alpha in the treatment of lupus will be presented this week at the American College of Rheumatology Annual Scientific Meeting in Chicago.

Systemic lupus erythematosus, also called SLE or lupus, is a chronic inflammatory disease that can affect the skin, joints, kidneys, lungs, nervous system, and/or other organs of the body. The most common symptoms include skin rashes and arthritis, often accompanied by fatigue and fever. Lupus occurs mostly in women, typically developing in individuals in their twenties and thirties - prime child-bearing age.

Interferon alpha (IFNa) is a protein (called a cytokine) made by cells of the immune system, which stimulates the production of autoantibodies in people with lupus. This stimulation of autoantibodies causes an attack on a person's immune system, and blocking cytokines is a potential target in the treatment of people with lupus.

Immunization to stop the effects of cytokines has already been proven beneficial in animals with lupus, and — for the first time — researchers have looked at an immunization strategy with INFa-kinoid in a study of people with lupus. In the IFNa-kinoid, the structure of the IFN cytokine is artificially modified by linking it to another molecule, called a carrier. This modified cytokine is then 'seen' by the immune system, and the immune system starts making antibodies against cytokines - ideally blocking their harmful effects in the body.

"Based on the pivotal role played by Type-I IFN (including IFNa) in the mechanisms underlying lupus, targeted therapy directed against this molecule might reduce the signs and symptoms of lupus, says the study's lead investigator, Frédéric Houssiau, MD, PhD; head of the Rheumatology Department and full professor of Rheumatology at Université catholique de Louvain, Brussels, Belgium. "The objective of our study was to demonstrate the safety and the feasibility of a new approach that uses the patient's own immune system against their IFNa."

Twenty-eight patients with mild to moderate, seropositive lupus were enrolled in the study, and the researchers looked at four dosage levels (30, 60, 120 and 240 milligrams) of INFa-kinoid, which were injected directly into the muscle on days zero, seven, 28 and (optionally) 84.

The researchers looked for any negative effects, as well as blood and biochemical responses that might occur with each dose. Responses in the immune system were assessed by using several different scoring systems that evaluate the degree of lupus disease activity.

The researchers found that immunization with IFNa-kinoid was safe - as only a few minor, short-term local and systemic reactions followed immunization, and only minor, short-term infections were reported. The only two serious negative reactions reported were two lupus flares: one in someone who received the immunization, and one in someone who received placebo.

All participants who received the immunization demonstrated an anti-IFNa antibody response, and these antibodies peaked and then declined after the last immunization was received.

"Anti-DNA antibodies and low complement are hallmarks of active lupus disease," says Dr. Houssiau. "Patients with such findings were, logically, found to have an IFNa signature; that is, they have elevated levels of genes related to IFNa. In this subset of patients, treatment with the IFNa-kinoid was able to turn down the IFNa signature safely."

The next step, according to Dr. Houssiau, is to design and to perform a trial to evaluate the drug's effectiveness.

Source: American College of Rheumatology

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