Lu sur https://www.ncbi.nlm.nih.gov/pubmed/28626780
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IgG-specific cell-based assay detects potentially pathogenic MuSK-Abs in seronegative MG.
Huda S1, Waters P1, Woodhall M1, Leite MI1, Jacobson L1, De Rosa A1, Maestri M1, Ricciardi R1, Heckmann JM1, Maniaol A1, Evoli A1, Cossins J1, Hilton-Jones D1, Vincent A1.
Neurol Neuroimmunol Neuroinflamm. 2017 Jun 5;4(4):e357. doi: 10.1212/NXI.0000000000000357. eCollection 2017 Jul.
To increase the detection of MuSK-Abs using a CBA and test their pathogenicity.
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.
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.
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.
- CLASSIFICATION OF EVIDENCE:
This study provides Class III evidence that an IgG-specific MuSK-CBA identifies patients with MG.