title: Clinical application of clustered-AChR for the detection of SNMG.
abstract: Myasthenia gravis (MG) is an autoantibody-mediated disease of the neuromuscular junction (NMJ). However, accumulating evidence has indicated that MG patients whose serum anti-acetylcholine receptor (AChR) antibodies are not detectable (serumnegative MG; SNMG) in routine assays share similar clinical features with anti-AChR antibody-positive MG patients. We hypothesized that SNMG patients would have low-affinity antibodies to AChRs that would not be detectable using traditional methods but that might be detected by binding to AChR on the cell membrane, particularly if they were clustered at the high density observed at the NMJ. We expressed AChR subunits with the clustering protein rapsyn (an AChR-associated protein at the synapse) in human embryonic kidney (HEK) cells, and we tested the binding of the antibodies using immunofluorescence. With this approach, AChR antibodies to rapsyn-clustered AChR could be detected in the sera from 45.83% (11/24) of SNMG patients, as confirmed with fluorescence-activated cell sorting (FACS). This was the first application in China of cell-based AChR antibody detection. More importantly, this sensitive (and specific) approach could significantly increase the diagnosis rate of SNMG.
authors.affiliation: Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, China.|Department of Neurology, Renji Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiutian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Renji Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yangtai
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Jiang
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D002462:Cell Membrane / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D009157:Myasthenia Gravis / Q000097:blood*; D011950:Receptors, Cholinergic / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics
chemical_list: D001323:Autoantibodies; D011950:Receptors, Cholinergic; D011994:Recombinant Proteins