LRP4 Autoimmune Reactivity in a Diverse Double-Seronegative Myasthenia Gravis Patient Population (P1.125)

Objective: To assess the frequency of low density lipoprotein receptor-related protein 4 (LRP4) autoimmune reactivity in a population of anti-acetylcholine receptor (AChR) and anti-muscle-specific kinase (MuSK) double-seronegative (DSN) myasthenia gravis (MG) patients. Background: LRP4, a receptor for agrin, has a central role in the formation of the neuromuscular junction. Autoantibodies to LRP4 have been identified in DSN MG cohorts at rates ranging from 0% to 54%, depending on the assay method and patient demographics. The clinical presentation of LRP4 antibody-positive patients is thought to be associated with a mild clinical course and a better response to therapy as compared to other myasthenia gravis subgroups. Design/Methods: We analyzed serum specimens from a demographically diverse population of DSN MG patients (n, mean age±SD, age range; 150, 60±17, 10–92) in the United States who had previously tested negative for AChR and MuSK autoantibodies. These specimens and normal healthy individuals (101, 38±12, 19–69) were tested for reactivity to LRP4 using a dual-labeled immunofluorescence assay. Results: Reactivity to LRP4 was found in 3% (4/150) of the DSN MG specimens but in none of the healthy controls. Of the 4 individuals who had LRP4 autoantibodies, generalized myasthenia gravis was reported in a 58-year-old man and isolated ptosis in a 50-year-old woman. Clinical information for the other two individuals with antibodies to LRP4 was not available. Conclusions: The results of this study suggest that LRP4 autoantibodies are present in a small percentage of DSN MG patients. Characterizing the clinical features of LRP4 antibody-positive individuals with MG may provide useful information regarding their prognosis and treatment response. Study Supported by: Quest Diagnostics Disclosure: Dr. Morneau has received personal compensation for activities with Quest Diagnostics as an employee. Dr. Sansoucy has received personal compensation for activities with Quest Diagnostics. Dr. Sansoucy has received research support from Quest Diagnostics. Dr. Goldberger has received personal compensation for activities with Quest Diagnostics as an employee. Dr. Trela has received personal compensation for activities with Quest Diagnostics as an employee. Dr. Clarke has received personal compensation for activities with Quest Diagnostics as an employee. Dr. Higgins has received personal compensation for activities with Quest Diagnostics.