Contactin-1 autoimmunity: Serologic, neurologic, and pathologic correlates

Neurol Neuroimmunol Neuroinflamm. 2020 May 27;7(4):e771. doi: 10.1212/NXI.0000000000000771. Print 2020 Jul.


Objective: To determine serologic characteristics, frequency, phenotype, paraneoplastic associations, and electrodiagnostic and histopathologic features accompanying contactin-1 autoimmunity.

Methods: Archived sera known to produce synaptic tissue-based immunofluorescence patterns were reevaluated, and contactin-1 specificity was confirmed by recombinant protein assays. Screening of 233 chronic/relapsing demyelinating neuropathies for additional cases was performed.

Results: We identified 10 contactin-1 IgG seropositive cases. Frequency of contactin-1 immunoglobulin (Ig) G among tested Mayo Clinic chronic/relapsing demyelinating neuropathies was 2%. Sensory predominant presentations (n = 9, 90%), neuropathic pain (n = 6, 60%), and subacute progression (n = 5, 50%) were commonly encountered among contactin-1 neuropathies. Two patients had chronic immune sensory polyradiculopathy-like phenotype at presentation. Electrodiagnostic studies were consistent with demyelination (slowed conduction velocities and/or prolonged distal latencies) without conduction block. Markedly elevated CSF protein (median 222 mg/dL, range 69-960 mg/dL), thickening/gadolinium enhancement of nerve roots (4/5), and subperineural edema on nerve biopsy (4/4) were other characteristic features. Three cases were diagnosed with paraneoplastic demyelinating neuropathies (thymoma, n = 1; breast cancer, n = 1; plasmacytoma, n = 1). Four of the 9 patients treated with IV immunoglobulin demonstrated initial clinical improvement, but the favorable response was sustained in only 1 case (median follow-up, 60 months). Sustained clinical stabilization or improvement was observed among 3 of the 6 cases in whom second-line therapies (rituximab, cyclophosphamide, and azathioprine) were used.

Conclusion: Contactin-1 IgG has a distinct sensory predominant presentation commonly associated with neuropathic pain, with demyelinating changes on electrophysiologic studies. A paraneoplastic cause should be considered. Testing of contactin-1 IgG among cases with similar presentations may guide immunotherapy selection, especially second-line immunotherapy consideration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Autoimmune Diseases of the Nervous System* / diagnosis
  • Autoimmune Diseases of the Nervous System* / metabolism
  • Autoimmune Diseases of the Nervous System* / pathology
  • Autoimmune Diseases of the Nervous System* / physiopathology
  • Contactin 1 / immunology*
  • Electrodiagnosis
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Young Adult


  • Autoantibodies
  • CNTN1 protein, human
  • Contactin 1