Antibodies against the node of Ranvier: a real-life evaluation of incidence, clinical features and response to treatment based on a prospective analysis of 1500 sera

Abstract

Introduction IgG4 antibodies against neurofascin (Nfasc155 and Nfasc140/186), contactin (CNTN1) and contactin-associated protein (Caspr1) are described in specific subtypes of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our objective was to assess, in a real-life practice, the incidence, the clinical features and the response to treatment of these forms of CIDP. Methods 1500 sera of patients suspected of having CIDP from France, Belgium and Switzerland were prospectively tested using a flow cytometry technique. The characteristics of patients with antibodies against the node of Ranvier were compared to 100 seronegative CIDP from our department. Results IgG4 antibodies against Nfasc155, CNTN1, and Caspr1 were, respectively, detected in 15 (prevalence 1%), 10 (0.7%) and 2 (0.2%) sera. Antibodies specific of the Nfasc140/186 were not detected. All subjects with antibodies against the node of Ranvier fulfilled diagnostic criteria for CIDP. CIDP with anti-Nfasc155 were younger, had more sensory ataxia and postural tremor than seronegative CIDP. CIDP with anti-CNTN1 had more frequent subacute onset and facial paralysis, commoner renal involvement with membranous glomerulonephritis and greater disability, than seronegative CIDP. CIDP with anti-Caspr1 had more frequent respiratory failure and cranial nerve involvement but not more neuropathic pain than seronegative CIDP. Intravenous immunoglobulins were ineffective in most seropositive patients. Rituximab produced dramatic improvement in disability and decreased antibodies titres in 13 seropositive patients (8 with anti-Nfasc155 and 5 with anti-CNTN1 antibodies). Conclusions Although rare, anti-paranodal antibodies are clinically valuable, because they are associated with specific phenotypes and therapeutic response.

Optic, trigeminal, and facial neuropathy related to anti‐neurofascin 155 antibody

“…Thus, the abnormal VEP frequency of 76.9% in the present NF155 + CIDP series is higher than the reported abnormal VEP frequencies in total CIDP patients, [29][30][31] which mostly reflects NF155 -CIDP cases, given the low frequency of NF155 + CIDP in Caucasians. [24][25][26] For VEP analysis, the monocular full visual field was stimulated; therefore, marked prolongation of P100 latencies in the absence of ophthalmological retinal lesions and occipital MRI lesions suggests the presence of subclinical demyelination in the optic nerves in most of our cases. NF155 is expressed in the terminal loop of not only Schwan cells but also oligodendrocytes; 32 therefore, it is reasonable that the optic nerves can be frequently affected by anti-NF155 antibodies.…”

“…In these previous studies, anti‐NF155 antibodies were not examined. However, the prevalence of anti‐NF155 antibodies is reported to be lower in Western countries (1% to 10% positive) 24–26 compared with Asian countries (18% and 21% positive); 14,27 therefore, it is conceivable that the results of these previous reports mostly reflected anti‐NF155 antibody‐negative (NF155 ‐ ) CIDP cases, particularly in the reports of Caucasians. Given that all NF155 + CIDP patients examined in this study had abnormal blink reflex, a higher frequency of blink reflex abnormalities is indicated for NF155 + compared with NF155 ‐ CIDP.…”

“…Head MRI of a 53-year-old female disease control patient with neuromyelitis optica spectrum disorder (NMOSD) (1-6) and of NF155 + CIDP patients (Case 8, 7-13; Case 9, 14-19; Case 12, 20-25, and Case 13, 26-31) are shown. Trigeminal nerve roots (the emitting portion of the trigeminal nerve from the brainstem)(1,7,14,20,26), intra-orbital ophthalmic and maxillary branches (2-4, 8-10, 15-17, 21-23, and 27-29) and mandibular branches at the level of the foramen ovale are shown in axial(5, 11, 18, 24 and 30) and coronal(6,12,19,25, and 31) views. The ophthalmic and maxillary branches (arrowheads) and mandibular branch (arrows) are identified in all NF155 + CIDP cases whereas these branches are hardly visible in the control.…”

Chronic inflammatory demyelinating polyradiculoneuropathy—Diagnostic pitfalls and treatment approach

“…If the case is indeed treatment‐refractory typical CIDP, combined PE and CCS or IVIg and CCS can be tried. In addition, patients with antibodies to neurofascin‐155 are refractory to IVIg but are quite sensitive to rituximab and probably PE, 75 whereas those with antibodies to contactin‐1 respond better to CCS than IVIg 76 . Irrespective of antibody status, rituximab appears to be a promising therapy even for antibody‐negative, treatment‐refractory CIDP, although not all patients respond 75 .…”

Anti-pan-neurofascin IgM in COVID-19-related Guillain-Barré syndrome: Evidence for a nodo-paranodopathy

“…Here, we describe a case of COVID-19-related Guillain-Barré syndrome in which clinical, pathobiological and neurophysiological evidence converged to suggest a paranodopathy with nodal involvement. Anti-neurofascin and anti-contactin antibodies were tested because of the absence of antiganglioside antibodies and according to the clinical phenotype (severe course, cranial nerve involvement and respiratory failure) [1] , [2] , [3] , [6] .…”