Potassium channel KIR4.1 clue to multiple sclerosis

By Stephanie Leveene

The potassium channel KIR4.1 is a potential immune target in certain patients with multiple sclerosis (MS), report researchers in TheNew England Journal of Medicine.

Bernhard Hemmer (Technical University Munich, Germany) and colleagues investigated whether the autoantibody response in MS has specific targets.

Serum samples from patients with MS were taken and compared with those from two control groups of healthy patients and patients with other neurologic conditions. Immunoglobulin (Ig)G antibodies were isolated and purified, revealing that IgG targeted brain glial cells in 58% of the patients with MS.

Serum from MS patients bound membrane proteins but not cytoplasmic proteins more avidly than serum from controls. Further analysis showed that IgG from MS serum specifically bound the central nervous system (CNS) membrane protein KIR4.1.

In total, nearly 47% of 397 patients with MS had KIR4.1 antibodies compared with approximately 1% of 329 patients with other neurologic diseases and 0% of 59 healthy controls.

There was no significant difference in KIR4.1 antibody prevalence between the different types of MS and no correlation between antibody positivity and clinical characteristics or age.

When KIR4.1 serum IgG was injected into cisternae magnae of mice, there was an alteration of glial fibrillary acidic protein and loss of KIR4.1 expression, suggesting that "multiple sclerosis-specific anti-KIR4.1 serum IgG can recognize its target antigen in the CNS and induce structural damage to glial cells," Hemmer et al say.

In a related editorial, Anne Cross (Washington University, St Louis, Missouri, USA) and Emmanuelle Waubant (University of California, San Francisco, USA) describe KIR4.1 as "an unexpected but plausible antigenic target."

They note that while autoantibodies do not play a primary role in MS pathology, they may perpetuate the breakdown of the CNS, which is a hallmark of the disease.

It is also possible that patients with MS who have KIR4.1 antibodies may not respond as well to current therapies. They conclude that "the specific role of antibodies to KIR4.1 in the pathogenesis of multiple sclerosis awaits further definition."

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