Clinical features of LRP4/agrin-antibody-positive myasthenia gravis: A multicenter study

Muscle Nerve. 2020 Sep;62(3):333-343. doi: 10.1002/mus.26985. Epub 2020 Jun 10.


Introduction: Our aim in this study was to identify the prevalence and clinical characteristics of LRP4/agrin-antibody-positive double-seronegative myasthenia gravis (DNMG).

Methods: DNMG patients at 16 sites in the United States were tested for LRP4 and agrin antibodies, and the clinical data were collected.

Results: Of 181 DNMG patients, 27 (14.9%) were positive for either low-density lipoprotein receptor-related protein 4 (LRP4) or agrin antibodies. Twenty-three DNMG patients (12.7%) were positive for both antibodies. More antibody-positive patients presented with generalized symptoms (69%) compared with antibody-negative patients (43%) (P ≤ .02). Antibody-positive patients' maximum classification on the Myasthenia Gravis Foundation of America (MGFA) scale was significantly higher than that for antibody-negative patients (P ≤ .005). Seventy percent of antibody-positive patients were classified as MGFA class III, IV, or V compared with 39% of antibody-negative patients. Most LRP4- and agrin-antibody-positive patients (24 of 27, 89%) developed generalized myathenia gravis (MG), but with standard MG treatment 81.5% (22 of 27) improved to MGFA class I or II during a mean follow-up of 11 years.

Discussion: Antibody-positive patients had more severe clinical disease than antibody-negative patients. Most DNMG patients responded to standard therapy regardless of antibody status.

Keywords: LRP4; agrin; clinical features; myasthenia gravis; neuromuscular transmission disorders; seronegative myasthenia gravis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Agrin / immunology*
  • Autoantibodies*
  • Female
  • Humans
  • LDL-Receptor Related Proteins / immunology*
  • Male
  • Middle Aged
  • Myasthenia Gravis / diagnosis*
  • Myasthenia Gravis / epidemiology
  • Myasthenia Gravis / immunology
  • Prevalence
  • Symptom Assessment
  • United States


  • Agrin
  • Autoantibodies
  • LDL-Receptor Related Proteins
  • LRP4 protein, human