Reviewed by Robert Jasmer, MD
; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Almost half of multiple sclerosis (MS) patients had potassium-channel autoantibodies associated with known or possible adverse effects on neural tissue, German investigators reported.
IgG antibodies to KIR4.1 occurred in 47% of almost 400 MS patients compared with fewer than 1% of patients with other neurologic conditions and none of 59 healthy serum donors.
KIR4.1 appears to represent the first autoantigen associated with multiple sclerosis, as reported online in the New England Journal of Medicine.
"The antibody is present in a subgroup of persons with multiple sclerosis -- 47% of the group that we analyzed -- and it has biologic effects in vivo," Bernhard Hemmer, MD, of the Technical University of Munich, and co-authors wrote in their summation.
"[Previously reported] observations, combined with the findings we describe here, suggest that KIR4.1 is a candidate autoantigen in multiple sclerosis," they added.
MS has an unknown etiology, uncertain pathogenic mechanism, clinical heterogeneity, and unpredictable therapeutic response, all of which contribute to the disease's complexity. Autoreactive T cells have been hypothesized as a key player in pathogenesis. However, several lines of evidence have implicated B-cell involvement, the authors noted in their introduction.
Direct evidence of clinically relevant autoantibodies in MS has remained elusive, though. Moreover, candidate molecular targets for humoral responses have emerged, they continued.
Recently, a specific serum autoantibody against water channel aquaporin-4 (AQP4) has been described in patients with neuromyelitis optica, historically considered an MS variant. Identification of the autoantibody suggests neuromyelitis optica is a distinct disease entity, providing impetus for new investigations to identify MS-specific autoantibody responses.
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