Objective: To increase the detection of MuSK-Abs using a CBA and test their pathogenicity. Methods: 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. Results: 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 (H1L) 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. Conclusions: 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. GLOSSARY AChEI 5 acetylcholinesterase inhibitor; CBA 5 cell-based assay; CI 5 confidence interval; DMEM 5 Dulbecco Modified Eagle Medium; FCS 5 fetal calf serum; HC 5 healthy control; HEK 5 human embryonic kidney; MG 5 myasthenia gravis; MGFA 5 Myasthenia Gravis Foundation of America; PSA 5 Penicillin, Streptomycin, and Amphotericin; RT 5 room temperature ; SNMG 5 seronegative MG. Several methods are available for the detection of antigen-specific antibodies (Abs) in the serum or CSF of patients with autoantibody-mediated CNS and peripheral nervous system diseases. 1 In the case of suspected autoimmune myasthenia gravis (MG), sera are routinely tested by radioimmunoprecipitation assays (RIAs) for Abs to AChR or MuSK. However, indirect immu-nofluorescence on live cells transiently transfected with AChRs and clustered by rapsyn, as they are at the neuromuscular junction, increases the detection of AChR-IgG 2-5 ; CBAs have been found to be sensitive and specific for many antibodies, e.g., for aquaporin-4 (AQP-4) antibodies in patients with neuromyelitis optica. 6 Here, to see whether a CBA might increase sensitivity for From the Nuffield Department of Clinical Neurosciences (

Jordan is a medium-high risk country for MS, with prevalence higher than what has previously been reported, possibly representing an increase in incidence. Clinical and demographic characteristics are similar to most reports worldwide.

Patients with MeS displayed more severe and extensive periodontal disease compared to subjects without MeS. Additional large-scale longitudinal epidemiologic and interventional studies are needed to establish whether periodontal disease is a contributing factor to or a result of MeS.