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Diederich, Jan-Markus; Staudt, Maximilian; Meisel, Christian; Hahn, Katrin; Meinl, Edgar; Meisel, Andreas; Klehmet, Juliane (2018): Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy Subtypes. In: Frontiers in Neurology, Vol. 9, 171
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Abstract

Objective: The 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 (PO 180-199) and myelin basic protein (MBP 82-100). Methods: Interferon-gamma (IFN-gamma) 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). Results: Compared to controls, MADSAM and sensory CIDP patients showed broadest IFN-gamma T cell responses to all four antigens. Positive IFN-gamma 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 (Cl) 0.82-1.00] compared to ON. For sensory CIDP, AUG of PO 180-199 was 0.94 (95% Cl 0.86-1.00) and for MBP 82-100 0.95 (95% Cl 0.88-1.00) compared to ON. Conclusion: Cell-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 PO 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.