Study Suggests Causes for Lupus' Impact on Immune System

Certain cells seem to malfunction and create inflammation instead of fighting the disease, research say

Tuesday, March 8, 2016

TUESDAY, March 8, 2016 (HealthDay News) -- Scientists have found new clues that help explain what's going wrong in the immune systems of people with lupus -- insight they hope will lead to new therapies, or help guide current treatment choices.

Lupus has several forms, but the most common is systemic lupus erythematosus (SLE). In SLE, the immune system mistakenly produces antibodies against the body's own tissue. The onslaught can have widespread effects, damaging the skin, joints, heart, lungs, kidneys and brain, according to the Lupus Foundation of America.

The disease mostly strikes women, usually starting in their 20s or 30s, the foundation says.

In the new study, the researchers found evidence that in people with lupus, some of the immune system's "B cells" mature the wrong way -- so that they promote inflammation instead of fighting it.

The findings, published online March 8 in the journal Immunity, could help in developing new lupus therapies, said senior researcher Claudia Mauri. She is a professor of immunology at University College London in the United Kingdom.

In people without lupus, anti-inflammatory B cells appear to prevent excessive production of a protein called interferon-alpha, explained Mauri.

That's a critical job because too much interferon-alpha leads to too many B cells that produce antibodies, the study authors said. Antibodies are necessary soldiers in the body's defense against infection, but in lupus, some of those antibodies target the body itself.

"We will continue to work to develop new [treatment] strategies that harness the anti-inflammatory B cells in patients with SLE," Mauri said.

Right now, a number of drugs are used to treat lupus, including immune-system suppressors such as cyclophosphamide and tacrolimus, and anti-malaria drugs like hydroxychloroquine -- which can ease the fatigue, joint pain and skin rash that lupus commonly causes, according to the Lupus Foundation of America.

In some cases, doctors try a drug called rituximab, an IV medication designed to kill off certain B cells. Rituximab is approved to treat certain cancers and rheumatoid arthritis -- another autoimmune disease; but some lupus patients respond to the medication, too, the study authors said.

It's been unclear, though, why only certain lupus patients see benefits from rituximab, according to the researchers. Mauri said the new findings suggest a reason. People's response to rituximab may depend on whether they have normal activity in two genes related to interferon-alpha.

That, Mauri said, suggests that lupus patients should have gene testing before they're placed on rituximab. But, she stressed, "long-term studies -- where patients get tested before, during and after treatment -- are needed to prove that hypothesis unequivocally."

A rheumatologist who was not involved in the study agreed. "At this point, more work is needed, including looking at feasibility and cost issues," said Dr. Rosalind Ramsey-Goldman, a professor of medicine at Northwestern University Feinberg School of Medicine, in Chicago.

Ramsey-Goldman also agreed that the findings could eventually lead to new therapies, or point researchers in the direction of existing drugs for other conditions that could be "repurposed" to fight lupus.

The findings are based on blood samples from nearly 100 healthy volunteers and 200 people with lupus. Mauri's team found that lupus patients seemed to have an imbalance among three types of immune cells: B cells that produce antibodies; B cells that regulate inflammation; and cells that produce interferon-alpha.

Essentially, there is a lack of anti-inflammatory B cells, which leads to overproduction of interferon-alpha. That, in turn, boosts that number of antibody-producing B cells, the study found.

The root cause of it all remains a mystery, however, Mauri said.

And not all lupus patients would have this particular abnormality, according to Ramsey-Goldman. "SLE is probably a syndrome with multiple different immune system abnormalities," she said.

In general, Ramsey-Goldman explained, lupus is thought to arise from a combination of genetic susceptibility to autoimmune diseases and certain environmental factors.

Researchers still don't know what those factors are. But the suspects include certain infections, such as the Epstein-Barr virus, and on-the-job exposure to silica dust, according to the Lupus Foundation of America.

SOURCES: Claudia Mauri, Ph.D., professor, immunology, University College London, U.K.; Rosalind Ramsey-Goldman, M.D., Dr.Ph., professor, medicine, Northwestern University Feinberg School of Medicine, Chicago; March 8, 2016, Immunity, online

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