Investigation of the KIR4.1 potassium channel as a putative antigen in patients with multiple sclerosis: a comparative study

被引:65
作者
Brickshawana, Adipong [1 ,3 ]
Hinson, Shannon R. [2 ]
Romero, Michael F. [4 ,5 ]
Lucchinetti, Claudia F. [3 ]
Guo, Yong [3 ]
Buttmann, Mathias [7 ]
McKeon, Andrew [2 ]
Pittock, Sean J. [2 ,3 ]
Chang, Min-Hwang [5 ]
Chen, An-Ping [5 ]
Kryzer, Thomas J. [2 ]
Fryer, James P. [2 ]
Jenkins, Sarah M. [6 ]
Cabre, Philippe [8 ]
Lennon, Vanda A. [1 ,2 ,3 ]
机构
[1] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA
[2] Mayo Clin, Dept Lab Med & Pathol, 200 First St SW, Rochester, MN 55905 USA
[3] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA
[4] Mayo Clin, Dept Hypertens & Nephrol, Rochester, MN 55905 USA
[5] Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN 55905 USA
[6] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA
[7] Univ Wurzburg, Dept Neurol, Wurzburg, Germany
[8] CHRU Ft France, Pierre Zobda Quitman Hosp, Fort De France, Martinique, France
基金
美国国家卫生研究院;
关键词
ENVIRONMENTAL RISK-FACTORS; NEUROMYELITIS-OPTICA; AQUAPORIN-4; ANTIBODIES; LESIONS; ENCEPHALITIS; AUTOIMMUNITY; DISORDERS; SPECTRUM; DISEASE;
D O I
10.1016/S1474-4422(14)70141-3
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background Antibodies have been implicated in the pathogenicity of multiple sclerosis by findings of immunoglobulins in patients' CSF and often IgG and complement in lesions, and by a 2012 report that nearly half of patients' serum samples contain IgG specific for a glial potassium-channel, KIR4.1. We aimed to establish the frequency of KIR4.1-binding IgG in serum and CSF of patients with multiple sclerosis, and whether KIR4.1 immunoreactivity is retained or lost in demyelinating lesions. Methods Using ELISA with a KIR4.1 peptide, we tested archival serum from 229 population-based and 57 dinic-based patients with multiple sclerosis, 99 healthy controls, and 109 disease controls, and CSF from 25 patients with multiple sclerosis and 22 disease controls. We tested all CSF and serum samples from 50 of the dinic-based patients with multiple sclerosis on cells expressing functional KIR4.1, using cell-based immunofluorescence and immunoprecipitation (solubilised recombinant human KIR4.1). We assessed KIR4.1 immunoreactivity in archival brain samples from 15 patients with histopathologically confirmed multiple sclerosis (22 plaques [eight early active, eight inactive, and six remyelinated], 13 periplaque regions and eight normal-appearing white-matter and grey-matter regions) and from three controls with non-neurological diseases. Findings Three of 286 serum samples from patients with multiple sclerosis and two of 208 serum samples from controls showed KIR4.1 reactivity on ELISA; none of the CSF samples from patients or controls showed KIR4.1 reactivity. IgG in none of the 50 serum samples from clinic-based patients immunoprecipitated KIR4.1, but a commercial KIR4.1-specific control IgG did. By immunofluorescence, one of 50 serum samples from patients with multiple sclerosis yielded faint plasmalemmal staining on both KIR4.1-expressing and non-expressing cells; 16 bound faintly to intracellular components. In all cases, IgG binding was quenched by absorption with liver powder or lysates from non-transfected cells. Binding by the KIR4.1-specific control IgG was quenched only by lysates containing KIR4.1. IgG in none of the 25 CSF samples from patients with multiple sclerosis bound to KIR4.1-transfected cells. Glial KIR4.1 immunoreactivity was increased relative to expression in healthy control brain in all active demyelinating lesions, remyelinated lesions, and periplaque white matter regions. Interpretation We did not detect KIR4.1-specific IgG in serum or C SF from patients with multiple sclerosis or KIR4.1 loss from glia in multiple sclerosis lesions. Serological testing for KIR4.1-specific IgG is unlikely to aid diagnosis of multiple sclerosis. The target antigen of multiple sclerosis remains elusive.
引用
收藏
页码:795 / 806
页数:12
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