title: Antibodies to contactin-1 in chronic inflammatory demyelinating polyneuropathy.
abstract: OBJECTIVE
  Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a frequent autoimmune neuropathy with a heterogeneous clinical spectrum. Clinical and experimental evidence suggests that autoantibodies may be involved in its pathogenesis, but the target antigens are unknown. Axoglial junction proteins have been proposed as candidate antigens. We examined the reactivity of CIDP patients' sera against neuronal antigens and used immunoprecipitation for antigen unraveling.
  
  
  METHODS
  Primary cultures of hippocampal neurons were used to select patients' sera that showed robust reactivity with the cell surface of neurons. The identity of the antigens was established by immunoprecipitation and mass spectrometry, and subsequently confirmed with cell-based assays, immunohistochemistry with teased rat sciatic nerve, and immunoabsorption experiments.
  
  
  RESULTS
  Four of 46 sera from patients with CIDP reacted strongly against hippocampal neurons (8.6%) and paranodal structures on peripheral nerve. Two patients' sera precipitated contactin-1 (CNTN1), and 1 precipitated both CNTN1 and contactin-associated protein 1 (CASPR1). Reactivity against CNTN1 was confirmed in 2 cases, whereas the third reacted only when CNTN1 and CASPR1 were cotransfected. No other CIDP patient or any of the 104 controls with other neurological diseases tested positive. All 3 patients shared common clinical features, including advanced age, predominantly motor involvement, aggressive symptom onset, early axonal involvement, and poor response to intravenous immunoglobulin.
  
  
  CONCLUSIONS
  Antibodies against the CNTN1/CASPR1 complex occur in a subset of patients with CIDP who share common clinical features. The finding of this biomarker may help to explain the symptoms of these patients and the heterogeneous response to therapy in CIDP.
authors.affiliation: Neuromuscular Diseases Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Querol
authors.forename: Gisela
authors.initials: G
authors.lastname: Nogales-Gadea
authors.forename: Ricard
authors.initials: R
authors.lastname: Rojas-Garcia
authors.forename: Eugenia
authors.initials: E
authors.lastname: Martinez-Hernandez
authors.forename: Jordi
authors.initials: J
authors.lastname: Diaz-Manera
authors.forename: Xavier
authors.initials: X
authors.lastname: Suárez-Calvet
authors.forename: Miquel
authors.initials: M
authors.lastname: Navas
authors.forename: Josefa
authors.initials: J
authors.lastname: Araque
authors.forename: Eduard
authors.initials: E
authors.lastname: Gallardo
authors.forename: Isabel
authors.initials: I
authors.lastname: Illa
mesh_terms: D000368:Aged; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000097:blood* / Q000494:pharmacology; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002478:Cells, Cultured; D058967:Contactin 1 / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006624:Hippocampus / Q000166:cytology / Q000473:pathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009431:Neural Conduction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000097:blood* / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000378:metabolism; D044967:Serum; D018709:Statistics, Nonparametric; D014162:Transfection
chemical_list: D000906:Antibodies; C548669:CNTN1 protein, human; C403049:CNTNAP2 protein, human; D015816:Cell Adhesion Molecules, Neuronal; D058967:Contactin 1; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins