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

Abstract

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.

• Authors: Divyanshu Dubey, Josephe A Honorat, Shahar Shelly, Christopher J Klein, Lars Komorowski, John R Mills, Stefanie Brakopp, Christian Probst, Vanda A Lennon, Sean J Pittock, Andrew McKeon
• Journal: Neurology(R) neuroimmunology & neuroinflammation (Neurol Neuroimmunol Neuroinflamm) Vol. 7 Issue 4 (07 2020) ISSN: 2332-7812 [Electronic] United States
• PMID: 32461352 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Chemical References

• Autoantibodies
• CNTN1 protein, human
• Contactin 1

Topics

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