title: Anti-agrin autoantibodies in myasthenia gravis.
abstract: OBJECTIVE
  Because the extracellular matrix protein agrin is essential for neuromuscular junction formation and maintenance, we tested the hypothesis that autoantibodies against agrin are present in sera from patients with myasthenia gravis (MG).
  
  
  METHODS
  We determined the presence of anti-agrin antibodies in 54 sera from patients with generalized MG using a solid-phase ELISA with purified mini-agrin protein. Thirty of the 54 sera were seronegative for antibodies against the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK), 15 had elevated levels of anti-MuSK, and 9 had elevated levels of anti-AChR autoantibodies. Sixteen sera from healthy volunteers served as control.
  
  
  RESULTS
  Five sera with elevated levels of anti-agrin antibodies were identified. The concentration of the antibodies ranged between 0.04 and 0.12 nM. Four of the 5 agrin-positive sera were also positive for anti-MuSK, one was positive for anti-AChR, and 2 had elevated levels of anti-low-density lipoprotein receptor-related protein 4 (LRP4) autoantibodies. Some of the sera stained adult mouse neuromuscular junctions and reacted with native mini-agrin expressed in 293HEK cells.
  
  
  CONCLUSIONS
  The results provide evidence for agrin as a novel target protein for autoantibodies in patients with MG. Anti-agrin antibodies were always detected in combination with autoantibodies against MuSK, LRP4, or AChRs, indicating a high incidence of autoantibodies against several neuromuscular proteins in the agrin-positive MG cases.
authors.affiliation: From the Institute for Physiology, Department of Physiological Genomics (C.G., Y.Z., J.M., S.K.), and Friedrich-Baur-Institute (B. Schoser), Ludwig-Maximilians University, Munich; Department of Neurology (B. Schalke), University of Regensburg; Department of Neurology (A.M.), University of Tübingen, Germany; and Laboratory of Molecular Biology of the Cell (V.R., L.S.), University of Lyon, France. A.M. is currently affiliated with the Department of Neurology, University Hospital Erlangen, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Gasperi
authors.affiliation: From the Institute for Physiology, Department of Physiological Genomics (C.G., Y.Z., J.M., S.K.), and Friedrich-Baur-Institute (B. Schoser), Ludwig-Maximilians University, Munich; Department of Neurology (B. Schalke), University of Regensburg; Department of Neurology (A.M.), University of Tübingen, Germany; and Laboratory of Molecular Biology of the Cell (V.R., L.S.), University of Lyon, France. A.M. is currently affiliated with the Department of Neurology, University Hospital Erlangen, Germany.
authors.forename: Arthur
authors.initials: A
authors.lastname: Melms
authors.affiliation: From the Institute for Physiology, Department of Physiological Genomics (C.G., Y.Z., J.M., S.K.), and Friedrich-Baur-Institute (B. Schoser), Ludwig-Maximilians University, Munich; Department of Neurology (B. Schalke), University of Regensburg; Department of Neurology (A.M.), University of Tübingen, Germany; and Laboratory of Molecular Biology of the Cell (V.R., L.S.), University of Lyon, France. A.M. is currently affiliated with the Department of Neurology, University Hospital Erlangen, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Schoser
authors.affiliation: From the Institute for Physiology, Department of Physiological Genomics (C.G., Y.Z., J.M., S.K.), and Friedrich-Baur-Institute (B. Schoser), Ludwig-Maximilians University, Munich; Department of Neurology (B. Schalke), University of Regensburg; Department of Neurology (A.M.), University of Tübingen, Germany; and Laboratory of Molecular Biology of the Cell (V.R., L.S.), University of Lyon, France. A.M. is currently affiliated with the Department of Neurology, University Hospital Erlangen, Germany.
authors.forename: Yina
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the Institute for Physiology, Department of Physiological Genomics (C.G., Y.Z., J.M., S.K.), and Friedrich-Baur-Institute (B. Schoser), Ludwig-Maximilians University, Munich; Department of Neurology (B. Schalke), University of Regensburg; Department of Neurology (A.M.), University of Tübingen, Germany; and Laboratory of Molecular Biology of the Cell (V.R., L.S.), University of Lyon, France. A.M. is currently affiliated with the Department of Neurology, University Hospital Erlangen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Meltoranta
authors.affiliation: From the Institute for Physiology, Department of Physiological Genomics (C.G., Y.Z., J.M., S.K.), and Friedrich-Baur-Institute (B. Schoser), Ludwig-Maximilians University, Munich; Department of Neurology (B. Schalke), University of Regensburg; Department of Neurology (A.M.), University of Tübingen, Germany; and Laboratory of Molecular Biology of the Cell (V.R., L.S.), University of Lyon, France. A.M. is currently affiliated with the Department of Neurology, University Hospital Erlangen, Germany.
authors.forename: Valerie
authors.initials: V
authors.lastname: Risson
authors.affiliation: From the Institute for Physiology, Department of Physiological Genomics (C.G., Y.Z., J.M., S.K.), and Friedrich-Baur-Institute (B. Schoser), Ludwig-Maximilians University, Munich; Department of Neurology (B. Schalke), University of Regensburg; Department of Neurology (A.M.), University of Tübingen, Germany; and Laboratory of Molecular Biology of the Cell (V.R., L.S.), University of Lyon, France. A.M. is currently affiliated with the Department of Neurology, University Hospital Erlangen, Germany.
authors.forename: Laurent
authors.initials: L
authors.lastname: Schaeffer
authors.affiliation: From the Institute for Physiology, Department of Physiological Genomics (C.G., Y.Z., J.M., S.K.), and Friedrich-Baur-Institute (B. Schoser), Ludwig-Maximilians University, Munich; Department of Neurology (B. Schalke), University of Regensburg; Department of Neurology (A.M.), University of Tübingen, Germany; and Laboratory of Molecular Biology of the Cell (V.R., L.S.), University of Lyon, France. A.M. is currently affiliated with the Department of Neurology, University Hospital Erlangen, Germany.
authors.forename: Bertold
authors.initials: B
authors.lastname: Schalke
authors.affiliation: From the Institute for Physiology, Department of Physiological Genomics (C.G., Y.Z., J.M., S.K.), and Friedrich-Baur-Institute (B. Schoser), Ludwig-Maximilians University, Munich; Department of Neurology (B. Schalke), University of Regensburg; Department of Neurology (A.M.), University of Tübingen, Germany; and Laboratory of Molecular Biology of the Cell (V.R., L.S.), University of Lyon, France. A.M. is currently affiliated with the Department of Neurology, University Hospital Erlangen, Germany. skroeger@LMU.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Kröger
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D018171:Agrin / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000097:blood / Q000276:immunology*; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology; D011978:Receptors, Nicotinic / Q000276:immunology
chemical_list: D018171:Agrin; D001323:Autoantibodies; C539275:CHRNG protein, human; D026502:LDL-Receptor Related Proteins; C551781:LRP4 protein, human; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases