Evaluation of KIR4.1 as an Immune Target in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS. Many findings suggest an autoimmune pathogenesis of MS. We recently identified a serum autoantibody against the inward rectifying potassium channel KIR4.1 in a subpopulation of adults and children affected by MS. The autoantibody binds to the extracellular domain of homotetrameric KIR4.1 complexes and seems to exert biological activity in vitro and vivo. Neuropathological studies revealed that KIR4.1 is widely expressed by oligodendrocytes and a subset of astrocytes in the subcortical white matter. In active MS lesions, we noted a loss of oligodendrocytes and perivascular astrocytes expressing KIR4.1. In early inactive MS lesions, apart from a general loss of oligodendrocytes we observed a differential loss of astrocytic KIR4.1 immunoreactivity but not of GFAP. Conversely, KIR4.1 immunoreactivity was restored along astrocytic fibers in late inactive MS lesions and found to be co-expressed with GFAP. In summary these findings suggest KIR4.1 as a target of the autoimmune response in MS and a possible role of the channel in the pathogenesis of disease.