Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy

Abstract

Background and objectives: To study the clinical and laboratory features of antineurofascin-155 (NF155)-positive autoimmune nodopathy (AN).

Methods: Patients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up.

Results: Forty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2-4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = -0.88, p < 0.001) and with maximum I-RODS achieved (r = -0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients.

Discussion: Anti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases.

Classification of evidence: This study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab.

Figure 1. Baseline Serum NfL in Anti-NF155 + Patients With AN and Healthy Controls

Patients with anti-NF155 + AN had significantly higher sNfL levels than HC. The line in the center represents the median value, and the whiskers indicate the interquartile range. AN = autoimmune nodopathy; CIDP = chronic inflammatory demyelinating polyradiculoneuropathy; HC = healthy control; NF155 = neurofascin-155; sNfL = serum neurofilament light chain.

Figure 2. Clinical Status, NF155 Titers, and sNfL Levels After Rituximab Treatment Induction: Kinetics

Rituximab treated anti-NF-155 patients with follow-up samples at regular time points show improvement in the mRS scale, a decrease in NF155 titers, and a decrease in sNfL levels starting on the third month of treatment infusion. The line in the center represents the median value, and the whiskers indicate the interquartile range. mRS = modified Rankin Scale; NF155 = neurofascin-155; NF155 = neurofascin-155; sNfL = serum neurofilament light chain.

Figure 3. Rituximab Treatment Response: Clinical Status, NF155 Titers, and sNfL Levels

Clinical improvement is present in patients treated with first-line therapies or rituximab but only the rituximab-treated group improved significantly. Anti-NF155 titers and sNfL levels decreased only in rituximab-treated group. The line in the center represents the median value, and the whiskers indicate the interquartile range. IVIg = IV immunoglobulin; mRS= modified Rankin Scale; NF155= neurofascin-155; sNfL= serum neurofilament light chain.