Anti-rituximab antibodies in patients with refractory autoimmune nodopathy with anti-neurofascin-155 antibody

Abstract

BackgroundRecent studies have reported that similar to other IgG4 autoimmune diseases, such as muscle-specific kinase antibody-associated myasthenia gravis, most anti-neurofascin-155 (anti-NF155) nodopathies respond well to rituximab treatment, regardless of the dosage. However, there are still a few patients for which rituximab is ineffective for unknown reasons. Currently, there are no studies on the mechanism of ineffective treatment with rituximab.MethodsA 33-year-old Chinese man presenting with numbness, tremor, and muscle weakness for 4 years was recruited for this study. Anti-NF155 antibodies were identified by cell-based assay and confirmed by immunofluorescence assay on teased fibers. The anti-NF155 immunoglobulin (IgG) subclasses were also detected by immunofluorescence assay. Anti-rituximab antibodies (ARAs) were quantitatively analyzed using enzyme-linked immunosorbent assay (ELISA), and peripheral B cell counts were determined by flow cytometry.ResultsThe patient exhibited anti-NF155 IgG4-antibody positivity. After the first round of rituximab infusion, the patient showed stratified outcomes with improvements in numbness, muscle weakness and ambulation. However, after three rounds of rituximab infusion, the patient’s symptoms deteriorated, and the numbness, tremor and muscle weakness returned. No obvious improvement was found after plasma exchange and another round of rituximab treatment. 14 days after the last treatment with rituximab, ARAs were detected. And the titers gradually decreased on day 28 and 60 but remained higher than normal. Peripheral CD19+ B cell counts were less than 1% within the 2-month period following the final rituximab administration.ConclusionsIn this study, ARAs presented in a patient with anti-NF155 nodopathy undergoing rituximab treatment and showed an unfavorable impact on rituximab efficacy. This is the first case to report the occurrence of ARAs in patients with anti-NF155 antibodies. We suggest that ARAs should be tested early during the initial intervention, especially in patients who respond poorly to rituximab treatment. In addition, we believe it is necessary to investigate the association between ARAs and B cell counts, their effect on clinical efficacy, and their potential adverse reactions in a larger cohort of patients with anti-NF155 nodopathy.

Case Report: Telitacicept in treating a patient with NF155+ autoimmune nodopathy: a successful attempt to manage recurrent elevated sero-anti-NF155 antibodies

“…Some researchers believe that pretreatment with PE and IA may aid in antibody clearance and expedite recovery, although this requires further investigation. There are also reports of NF155+ AN patients producing anti-rituximab antibodies post-treatment, diminishing rituximab’s efficacy ( 16 ). In our case, the initial treatment with PE and rituximab was unsuccessful in improving the patient’s clinical symptoms, and anti-NF155 antibody titers even increased significantly ( Figure 1B ).…”

Exploring the depths of IgG4: insights into autoimmunity and novel treatments

“…This variability in response is likely due to the heterogeneity of the underlying immunopathologies ( 59 ) and an increasing significance of long-lived plasma cells in the immunopathogenesis as the disease progresses over time. In some instances, disease progression occurred post-anti-CD20 mediated BCDT administration ( 205 ), potentially linked to the presence of anti-RTX antibodies, known to impede responsiveness of anti-CD20 mediated BCDT in IgG4-mediated nodo-paranodopathies ( 206 ). Ocrelizumab, another BCDT targeting CD19 with lower immunogenic potential, has proven to be a successful alternative in patients developing anti-RTX mAbs ( 207 ).…”

Current Findings on the Spectrum of Neuronal Autoantibodies Associated with Psychotic Disorders

“…This evidence deserves further investigation in large-scale studies. While neurofascin 155 (NF155) autoantibodies have also appeared in schizophrenia and healthy controls (Daguano Gastaldi et al, 2022), they are unlikely to be of pathogenically significant, as they are more likely to coincide with neuromuscular peripheral nervous system disorders (Tan et al, 2022;Bai et al, 2023) and are involved in impaired electrical nerve conduction. Below we discuss autoantibodies against membrane surface antigens in 4.1 and autoantibodies against intracellular antigens in 4.2 and autoantibodies against unknown not further specified antigens in 4.3 (see Table 1 for details of described studies).…”