Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy Subtypes

Abstract

ObjectiveThe objective of this study is to investigate whether chronic inflammatory demyelinating polyneuropathy (CIDP) and its subtypes differ in their type 1 T-helper (TH1) cell response against nodal/paranodal neurofascin (NF186, NF155) as well as myelin protein zero (P0 180–199) and myelin basic protein (MBP 82–100).MethodsInterferon-gamma (IFN-γ) enzyme-linked immunospot assay was used to detect antigen-specific T cell responses in 48 patients suffering typical CIDP (n = 18), distal acquired demyelinating polyneuropathy (n = 8), multifocal acquired demyelinating sensory and motor polyneuropathy (MADSAM; n = 9), and sensory CIDP (n = 13) compared to other non-immune polyneuropathy (ON; n = 19) and healthy controls (n = 9).ResultsCompared to controls, MADSAM and sensory CIDP patients showed broadest IFN-γ T cell responses to all four antigens. Positive IFN-γ responses against two or more antigens were highly predictive for CIDP (positive predictive value = 0.95) and were found in 77% of CIDP patients. Patients with limited antigen-specific response were females, more severely affected with neuropathic pain and proximal paresis. The area under the receiver operating characteristics curve (AUC) of NF186 in MADSAM was 0.94 [95% confidential interval (CI) 0.82–1.00] compared to ON. For sensory CIDP, AUC of P0 180–199 was 0.94 (95% CI 0.86–1.00) and for MBP 82–100 0.95 (95% CI 0.88–1.00) compared to ON.ConclusionCell-mediated immune responses to (para)nodal and myelin-derived antigens are common in CIDP. TH1 response against NF186 may be used as a biomarker for MADSAM and TH1 responses against P0 180–199 and MBP 82–100 as biomarkers for sensory CIDP. Larger multicenter studies study are warranted in order to establish these immunological markers as a diagnostic tools.

The immune response and aging in chronic inflammatory demyelinating polyradiculoneuropathy

“…Immune cells Regarding specific immune cells that may be involved in anti-NF155-positive CIDP, one study was interested in studying autoreactive Th1 cell responses against NF155, NF186, P0 (aa 180-199), and myelin basic protein (MBP) (aa 82-100) in typical CIDP and its variants [92]. Using IFN-γ enzyme-linked immunosorbent assay (ELISA), the authors found more instances of IFNγ secretion in response to NF155 by PBMCs derived from typical CIDP patients (9/18 patients) compared to other non-immune neuropathy (ON) patients and healthy controls.…”

T Cells as an Emerging Target for Chronic Pain Therapy

“…In another study in CRPS patients, the number of Tregs did not change, but the specific sub-subset of CD39+ Treg was decreased (Heyn et al, 2019). In contrast, a stronger Th1 response was observed in T cells from patients with neuropathic pain as compared to controls when the cells were stimulated in vitro with myelin-derived antigen (Diederich et al, 2018). Further analysis reported changes in specific markers for sub-subsets of T cells.…”

Autoantibodies Against the Node of Ranvier in Seropositive Chronic Inflammatory Demyelinating Polyneuropathy: Diagnostic, Pathogenic, and Therapeutic Relevance

“…The paranodal localization of NF155 suggests that disruption of the paranodal structure may be necessary before autoantibodies are able to bind in vivo ( 68 , 69 ). Recently, neurofascin and compact myelin antigen-specific T cell response pattern have been analyzed in CIDP subtypes ( 79 ).…”