Clinical Characterization of Neurofascin-155 IgG4 and Contactin-1 IgG Dual Positive Neuropathies
Shemonti Hasan1, Haidara Kherbek1, Pallab Sarker1, Jae Nam1, Aaron Berkowitz3, Alan Salgado4, Kyle Wuthrich5, Christopher Klein2, John Mills2, Divyanshu Dubey2
1Neurology, Mayo Clinic, 2Mayo Clinic, 3University of California San Franscisco, 4Neurology, University of Michigan, 5USF Health Neurology
Objective:
To evaluate the frequency and characterize the clinical phenotype of patients positive for both neurofascin-155 and contactin-1 antibodies.
Background:
Clinical features associated with neurofascin-155 IgG4 or contactin-1 IgG seropositive autoimmune nodopathies have been described. However, clinical description of those with neurofascin-155 and contactin-1 autoantibody dual positive is lacking
Design/Methods:
Patients were identified through service neural autoantibody evaluation at Mayo Clinic Neuroimmunology Laboratory. Clinical information was gathered from the managing provider.
Results:
Among 1194 patients tested for autoimmune nodopathy panel between August 2022 and October 2023, 10 (0.8%; 1 female, 9 male) were positive for both antibodies. Clinical information was available for six patients. Median age of symptom onset was 64 years (range: 33-82). All patients were clinically and electrodiagnostically suspected to have chronic inflammatory demyelinating polyneuropathy. Median time from symptom onset to nadir was four months (range: 1.5-6). Among patients who underwent CSF evaluation (n=4), median nucleated cell count was 2.5 cells/mm3 (range: 1-9), and median protein was 255 mg/dL (range: 59-627). All nerve conduction studies (NCS) demonstrated polyradiculoneuropathy phenotype. Only one NCS was purely demyelinating but the majority (5/6, 83%) had features of demyelination and co-existing axonal loss. Additional symptoms included neuropathic pain (3, 50%), cranial neuropathy (3, 50%), dysautonomia (2, 33%), ataxia (5, 83%) and tremors (2, 33%). Membranous glomerulonephropathy was confirmed in one (17%). Median modified Rankin score at nadir was 5 (range: 3-5) and following immunotherapy including rituximab was 1 (range: 1-5) at the last follow up (n=5), with three improving by >1 point
Conclusions:
Neurofascin-155 and contactin-1 autoantibody dual seropositivity is rarely encountered. Our study demonstrates these patients have clinical features and treatment response resembling other neurofascin-155/contactin-1 IgG autoimmune nodopathies. Additional experimental studies are needed to evaluate the clinical and analytical specificity of these antibody results.