Long term follow-up in anti-contactin-1 autoimmune nodopathy

Objective To analyze long-term clinical and biomarker features of anti-contactin-1 (CNTN1) autoimmune nodopathy (AN). Methods Patients with anti-CNTN1+ AN detected in our laboratory from which clinical information was available were included. Clinical features and treatment response were retrospectively collected. Autoantibody, serum neurofilament light (sNfL) and serum CNTN1 levels (sCNTN1) were analyzed at baseline and follow-up. Results Thirty-one patients were included. Patients presented with progressive motor-sensory neuropathy (76.7%) with proximal (74.2%) and distal involvement (87.1%), ataxia (71.4%) and severe disability (median INCAT at nadir of 8)). Eleven patients (35%) showed kidney involvement. Most patients (97%) received IVIg but only one achieved remission with IVIg. Twenty-two patients (71%) received corticosteroids, and three of them (14%) did not need further treatments. Rituximab was effective in 21/22 patients (95.5%), with most of them (72%) receiving a single course. Four patients (12.9%) relapsed after a median follow-up of 25 months after effective treatment [12-48]. Anti-CNTN1 titers correlated with clinical scales at sampling and were negative after treatment in all patients but one (20/21). sNfL levels were significantly higher and sCNTN1 significantly lower in anti-CNTN1+ patients than in healthy controls (sNfL: 135.9 pg/mL vs 7.48 pg/mL, sCNTN1: 25.03 pg/mL vs 22186 pg/mL, p< 0.0001). Both sNfL and sCNTN1 returned to normal levels after successful treatment. Interpretation Patients with anti-CNTN1+ AN have a characteristic clinical profile. Clinical and immunological relapses are infrequent after successful treatment, suggesting that continuous treatment is unnecessary. Anti-CNTN1 antibodies, sNfL and aCNTN1 levels are useful to monitor disease status and treatment efficacy in these patients.