Figure - available from: Journal of Central Nervous System Disease
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Visual symptoms, MRI optic lesion and VEP findings in relation to anti-NF 155 antibodies among CCPD/CIDP patients from major published cohorts.
Source publication
Optic nerve demyelination is one of the clinical features of combined central and peripheral demyelination (CCPD), an entity with heterogenous immunopathogenesis and clinical characteristics, overlapping between multiple sclerosis (MS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Of interest, earlier studies among patients with CID...
Citations
... These antibodies were found to mediate axonal damage and exacerbate clinical disease in animal models of MS. However, it later transpired that these antibodies were not specific to MS and were found in a subset of patients with chronic inflammatory demyelinating polyneuropathy and also in some patients with combined CNS and PNS demyelination [53][54][55][56] . ...
... Pathogenic autoantibodies need to recognize an epitope that is expressed on the surface of Functional roles in demyelinating disease have also been proposed for antibodies that target nodal and paranodal proteins such as NF155 and NF186 [53][54][55][56] . In most cases with these antibodies, IgG4 is the predominant subclass of these antibodies, so the underlying mechanism could be steric interference with their target antigen rather than immune-mediated damage 96 . ...
... Some patients with combined CNS and PNS demyelination have been found to harbour antibodies against nodal and/or paranodal proteins [53][54][55][56] . When such antibodies are identified, we could investigate whether these patients remain part of the disease spectrum of MS or whether they, like patients with AQP4 or MOG antibodies, have a condition that is pathogenetically distinct from the overall MS population. ...
The role of autoantibodies in multiple sclerosis (MS) has been enigmatic since the first description, many decades ago, of intrathecal immunoglobulin production in people with this condition. Some studies have indicated that MS pathology is heterogeneous, with an antibody-associated subtype — characterized by B cells (in varying quantities), antibodies and complement — existing alongside other subtypes with different pathologies. However, subsequent evidence suggested that some cases originally diagnosed as MS with autoantibody-mediated demyelination were more likely to be neuromyelitis optica spectrum disorder or myelin oligodendrocyte glycoprotein antibody-associated disease. These findings raise the important question of whether an autoantibody-mediated MS subtype exists and whether pathogenic MS-associated autoantibodies remain to be identified. Potential roles of autoantibodies in MS could range from specific antibodies defining the disease to a non-disease-specific amplification of cellular immune responses and other pathophysiological processes. In this Perspective, we review studies that have attempted to identify MS-associated autoantibodies and provide our opinions on their possible roles in the pathophysiology of MS. Numerous studies have attempted to identify pathogenic autoantibodies in people with multiple sclerosis (MS), but their results are conflicting. In this Perspective, the authors explore the available evidence and provide their own opinions on a possible role for autoantibodies in MS.
Background
The frequency of nodal‐paranodal antibodies in HIV‐infected patients with chronic immune mediated radiculo‐neuropathies (IMRN) has not been previously described.
Methods
HIV‐infected patients who met the inclusion criteria for chronic IMRN were screened for IgG antibodies directed against nodal (neurofascin (NF)186) and paranodal (NF155, contactin‐1 (CNTN1) and contactin‐associated protein, Caspr1) cell adhesion molecules, using a live, cell‐based assay.
To explore potential pathogenicity, binding of human IgG to myelinated co‐cultures was assessed by incubation with patients’ sera positive for nodal or paranodal antibodies. Normal human serum was added as a source of complement to assess for complement activation as a mechanism for myelin injury.
Results
Twenty‐four HIV‐infected patients with IMRN were included in the study, 15 with CIDP, 4 with ventral root radiculopathies (VRR) and 5 with dorsal root ganglionopathies (DRG). Five patients with CIDP had combined central and peripheral demyelination. Three patients (12.7 %) tested positive for neurofascin IgG1 antibodies in the following categories: 1 patient with VRR was NF186 positive and 2 patients were NF155 positive with DRG and mixed sensory‐motor demyelinating neuropathy with optic neuritis respectively.
Conclusion
The frequency of nodal‐paranodal antibodies is similar among IMRN regardless of HIV status. Interpretation of the results in the context of HIV is challenging as there is uncertainty regarding pathogenicity of the antibodies, especially at low titres. Larger prospective immune studies are required to delineate pathogenicity in the context of HIV, and to establish a panel of antibodies to predict for a particular clinical phenotype.
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