Abstract | BACKGROUND: METHODS: Using ELISA with a KIR4.1 peptide, we tested archival serum from 229 population-based and 57 clinic-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 clinic-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: FUNDING: The National Institutes of Health, the National Multiple Sclerosis Society, and the Mayo Clinic Robert and Arlene Kogod Center on Aging.
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Authors | Adipong Brickshawana, Shannon R Hinson, Michael F Romero, Claudia F Lucchinetti, Yong Guo, Mathias Buttmann, Andrew McKeon, Sean J Pittock, Min-Hwang Chang, An-Ping Chen, Thomas J Kryzer, James P Fryer, Sarah M Jenkins, Philippe Cabre, Vanda A Lennon |
Journal | The Lancet. Neurology
(Lancet Neurol)
Vol. 13
Issue 8
Pg. 795-806
(Aug 2014)
ISSN: 1474-4465 [Electronic] England |
PMID | 25008548
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Ltd. All rights reserved. |
Chemical References |
- Autoantigens
- Biomarkers
- Immunoglobulin G
- Kcnj10 (channel)
- Potassium Channels, Inwardly Rectifying
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Autoantigens
(blood, cerebrospinal fluid, immunology)
- Biomarkers
(blood, cerebrospinal fluid)
- Child
- Female
- Humans
- Immunoglobulin G
(biosynthesis, blood, cerebrospinal fluid)
- Male
- Middle Aged
- Multiple Sclerosis
(blood, cerebrospinal fluid, diagnosis)
- Population Surveillance
- Potassium Channels, Inwardly Rectifying
(blood, cerebrospinal fluid)
- Protein Binding
(physiology)
- Young Adult
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