KIR4.1 Antibodies in Blood May Precede MS by Years

Antibodies against the inward rectifying potassium channel (KIR4.1) protein may be present in blood of healthy patients destined to develop multiple sclerosis (MS), results of a small study suggest.

"If our results can be replicated in larger populations, our findings may help to detect MS earlier in a subgroup of patients," said study author Viola Biberacher, MD, from the Technical University in Munich, Germany. "Finding the disease before symptoms appear means we can better prepare to treat and possibly even prevent those symptoms," she added.

The results were released February 21 and will be presented at the upcoming 66th Annual Meeting of the American Academy of Neurology (AAN) in Philadelphia, Pennsylvania, in April.

Toward a Blood Test for MS?

Antibodies against KIR4.1 have been found in some people with clinically isolated syndrome or MS. "However, it is unknown whether the antibody response to KIR4.1 precedes the onset of MS or emerges after the disease already is established," Dr. Biberacher and colleagues note in a meeting abstract.

To investigate, they screened plasma from 16 healthy blood donors with subsequent diagnosis of MS (pre-MS) and an equal number of age- and sex-matched healthy blood donors who did not develop MS for KIR4.1-specific antibodies using an enzyme-linked immunosorbent assay. The samples were collected 2 to 9 months before the first clinical attack of MS.

Pre-MS patients had a significantly higher KIR4.1 antibody titer than their healthy peers (P = .0185), the investigators found. Seven pre-MS patients were considered positive for KIR4.1 antibodies, 2 showed borderline activity, and 7 were negative.

In contrast, all 16 healthy controls tested negative for the KIR4.1 antibody.

In a longitudinal analysis looking at additional time points up to 6 years before and after disease onset, KIR4.1 antibodies were found in pre-MS patients several years before the first clinical attack.

The finding that KIR4.1 antibodies may develop years before MS onset suggests "a role of the autoantibody in how the disease develops," Dr. Biberacher said in a statement.

"The next step is to confirm these findings in larger groups and determine how many years before onset of disease the antibody response develops," she added.

"Interesting" Finding in "Multifactorial" Disease

Lily K. Jung-Henson, MD, a neurologist specializing in MS at the Swedish Medical Center, Seattle, Washington, said, "The key finding is the presence of KIR4.1 antibodies in patients who develop MS, and absence in those who do not go on to develop MS."

Dr. Jung-Henson said it's also interesting in terms of subsequent risk for MS that as many people developed antibodies as those who did not. "This suggests that the development of MS is multifactorial, and even if KIR4.1 antibodies are implicated, it is not a wholesale process," she told Medscape Medical News.

The study was supported by the German Federal Ministry of Education and Research. The authors have disclosed no relevant financial relationships. Dr. Jung-Henson was principal investigator in the CARE MS 2 phase 3 trial of alemtuzumab and also had a major involvement in fingolimod and BG-12 trials.

66th Annual Meeting of the American Academy of Neurology (AAN), April 26 to May 3, 2014. Abstract 3211.

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