Immune System Glitch Linked to Four Times Higher Risk of Death

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People with an immune system flaw that causes the overproduction of an antibody molecule called a free light chain are four times more likely to die of diseases including cancer, diabetes and cardiac and respiratory disease than those with normal levels, according to researchers from the Mayo Clinic.

In the study, the research team evaluated blood samples from nearly 16,000 people age 50 and older who were enrolled in a population-based study of plasma cell disorders in Olmsted County, Minn. Participants with the highest levels of free light chains, those in the top 10%, were nearly four times more likely to die than people with lower levels.

Even after the team accounted for other factors that could affect likelihood of death, such as age, gender and kidney function, people with high levels of free light chains were at twice the risk.

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The researchers suggest that high levels of free light chains may indicate an increased immune response to infection, inflammation, or some other serious disorder. Previous research in patients with plasma disorders such as lymphoma or and other blood cancers has shown that those with high levels of free light chains have an increased risk of death, but the current study suggests the risk may apply to the general population too.

Measuring free light chain levels is as easy as a blood test. This is usually done to monitor the levels in patients with plasma disorders to assess how they are responding to treatment. Dr. Vincent Rajkumar, a Mayo Clinic hematologist and lead author of the new study, and his colleagues first noted the association between free light chains and death risk during earlier research of melanoma precursors.

“It’s interesting that levels that are abnormal years prior to an event can be a predictor. A test that tells you something about a patient before anything adverse occurs is valuable,” says Rajkumar.

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Still, Rajkumar cautions that patients should not start relying on the test to determine their death risk. “We do not recommend this test as a screening test because it will only cause alarm,” he says. “We do not know why this is associated with higher rates of death. You typically screen when you know how to treat what you are screening for. We do not yet know what to do about it, so until then, we recommend caution.”

The findings may still have some immediate use for patient care, however. “This can help patients who come in with unspecified complaints. If physicians are aware of the study, they can further pursue what’s wrong with the patient even if they cannot determine what is ailing them right then,” says Rajkumar.

More research is needed to determine the precise mechanisms that underlie the association between high levels of free light chains and death risk, and ultimately, to identify whether interventions can reduce that risk.

The study was published in the June issue of Mayo Clinic Proceedings.

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