Researchers at the Mayo Clinic measured levels of the immune-system molecules known as free light chains in 15,859 Minnesotans age 50 and up, and found that people whose levels were in the top 10% were four times more likely than the other study participants to die over the next 13 years.
Doctors commonly test for free light chains to diagnose and manage blood disorders and blood-related cancers, such as multiple myeloma or lymphoma. This study, which was published this week in the journal Mayo Clinic Proceedings, is the first to link high levels of free light chains with earlier death in a group of people without any known blood disorders.
Normally, light chains bind with so-called heavy chains to form infection-fighting antibodies. The presence of unattached “free” light chains has long been recognized as a signal that the immune system has gone awry, either due to inflammation, infection, or both, says lead author Vincent Rajkumar, M.D., a hematologist at the Mayo Clinic, in Rochester, Minn.
Elevated free light chain levels have been observed in people with kidney dysfunction, and are also seen in autoimmune disorders such as rheumatoid arthritis and lupus. Even after the researchers took into account the kidney function, age, and gender of the participants, however, those with the highest free light chain levels were still twice as likely as their peers to die during the study.
Free light chain levels appeared to be equally effective at predicting death from many different causes, including cancer, heart disease, lung disease, and diabetes.
It’s not clear from the findings why, exactly, free light chains are linked to a higher risk of early death. High levels could be a marker of inflammation, which is associated with heart disease and numerous other health problems. But it’s also possible they’re a sign of normal, age-related deterioration of the immune system, the study notes.
And it’s still unclear how this test might be useful in generally healthy people. For now, Rajkumar and his colleagues urge doctors not to use the test as a screening instrument, as that will simply serve to alarm patients.
On the other hand, Rajkumar says, if doctors order the test for a specific reason and it comes back high, they may want to use that information to test for additional problems that could then be treated. “It might be telling you something you might be missing,” he says.
Neil Blumberg, M.D., a professor of pathology and laboratory medicine at the University of Rochester Medical Center, in Rochester, N.Y., says he’s skeptical that free light chain tests are more powerful than existing tests that measure immune-system function or markers of inflammation, such as C-reactive protein.
The study authors didn’t compare the free light chain test with these other tests, Blumberg points out, and it “may not measure anything that we don’t get with white cell count or C-reactive protein or 15 other tests which are cheaper and easier to do.”
Besides, Blumberg says, if a person’s test results were to come back sky-high, the advice for preventing an early death would likely be what patients hear from their doctors already. “We really don’t need any more tests to tell us we ought to lose weight, exercise, [and] eat a less pro-inflammatory diet,” he says.