Abstract

Myasthenia Gravis (MG) is an autoimmune disease characterised by a defect in the transmission of nerve impulses to muscles. Patients with a diagnosis of MG may test negative for both acetylcholine receptor (AChR) and muscle specific kinase (MuSK) antibodies on conventional immunoprecipitation assays. These patients are often termed seronegative (SNMG). Recent studies using cell-based assays have demonstrated the presence of low affinity IgG antibodies, with complement activating abilities that bind preferentially to clustered AChRs or MuSK on transfected cell membranes. Our objectives were (1) to audit the investigation of suspected MG at Addenbrooke's hospital. (2) To identify SNMG patients and test for sera AChR and MuSK antibodies using cell-based assays. (3) To test for low affinity antibodies at different stages of disease. We identified seven SNMG patients, one positive for low affinity MuSK and one positive for low affinity AChR antibodies respectively. Another individual was positive for AChR antibodies by the cell-based assay from the first serum sample, whereas the conventional assay showed positivity only in the sample taken 8 months later. This study highlights the potential importance of cell based assays for diagnosis and management of MG. The detection of antibodies in early stages of disease suggests the initial autoimmune response may be dominated by low affinity antibodies.

AV and her department receive royalties and payments for antibody assays.