Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

<jats:sec><jats:title>Objective:</jats:title><jats:p>To increase the detection of MuSK-Abs using a CBA and test their pathogenicity.</jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p>Sera from 69 MuSK-RIA–positive patients with myasthenia gravis (MG) (Definite MuSK-MG), 169 patients negative for MuSK-RIA and AChR-RIA (seronegative MG, SNMG), 35 healthy individuals (healthy controls, HCs), and 16 NMDA receptor-Ab–positive (NMDAR-Ab) disease controls were tested for binding to MuSK on a CBA using different secondary antibodies.</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>Initially, in addition to 18% of SNMG sera, 11% of HC and 19% of NMDAR-Ab sera showed positive binding to MuSK-transfected cells; this low specificity was due to anti-IgG(H+L) detection of IgM bound nonspecifically to MuSK. Using an IgG Fc gamma-specific secondary antibody, MuSK-Abs were detected by CBA in 68/69 (99%) of Definite MuSK-MG, 0/35 HCs, 0/16 NMDAR-Ab, and 14/169 (8%) of SNMG sera, providing increased sensitivity with high specificity. The RIA-negative, CBA-positive MuSK-IgG sera, but not IgM-MuSK–binding sera, reduced agrin-induced AChR clustering in C2C12 myotubes, qualitatively similar to RIA-positive MuSK-Abs.</jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p>An IgG-specific MuSK-CBA can reliably detect IgG MuSK-Abs and increase sensitivity. In the MuSK-CBA, IgG specificity is essential. The positive sera demonstrated pathogenic potential in the in vitro AChR-clustering assay, although less effective than Definite MuSK-MG sera, and the patients had less severe clinical disease. Use of IgG-specific secondary antibodies may improve the results of other antibody tests.</jats:p></jats:sec><jats:sec><jats:title>Classification of evidence:</jats:title><jats:p>This study provides Class III evidence that an IgG-specific MuSK-CBA identifies patients with MG.</jats:p></jats:sec>

Original publication

DOI

10.1212/nxi.0000000000000357

Type

Journal article

Journal

Neurology - Neuroimmunology Neuroinflammation

Publisher

Ovid Technologies (Wolters Kluwer Health)

Publication Date

07/2017

Volume

4

Pages

e357 - e357