Novel Immune Target Identified in Multiple Sclerosis
About half of a subgroup of patients have antibodies against a brain potassium channel
WEDNESDAY, July 11 (HealthDay News) -- About half of a subgroup of patients with multiple sclerosis have autoantibodies to a potassium channel in the brain, according to a study published in the July 12 issue of the New England Journal of Medicine.
To identify the target of the immune response in multiple sclerosis, Rajneesh Srivastava, from the Technische Universität in Munich, Germany, and colleagues screened serum immunoglobulin G (IgG) from a subgroup of patients with multiple sclerosis who displayed specific binding of IgG to glial cells. Results were validated in other groups of patients with multiple sclerosis.
The researchers found that the membrane protein ATP-sensitive inward rectifying potassium channel (KIR4.1) was the target of the IgG autoantibodies. In the combined datasets analyzed, antibodies to KIR4.1 were present in 46.9 percent of patients with multiple sclerosis, 0.9 percent of patients with other neurological diseases, and no healthy individuals. These antibodies bound to KIR4.1 on the first extracellular loop. Following injection of KIR4.1 serum IgG from multiple sclerosis patients into the cisternae magnae of mice there was loss of KIR4.1 expression, expression of glial fibrillary acidic protein was altered in astrocytes, and the complement cascade was activated where KIR4.1 was expressed in the cerebellum.
"In summary, putting aside a priori assumptions in the search for autoantigens in multiple sclerosis, these investigators took an unbiased approach that resulted in the identification of an unexpected but plausible antigenic target," write the authors of an accompanying editorial. "The specific role of antibodies to KIR4.1 in the pathogenesis of multiple sclerosis awaits further definition."
Several authors disclosed financial relationships with pharmaceutical and biotechnology companies.
Full Text (subscription or payment may be required) (http://www.nejm.org/doi/full/10.1056/NEJMoa1110740 )Editorial (subscription or payment may be required) (http://www.nejm.org/doi/full/10.1056/NEJMe1204118 )