Anti-MAG IgM: differences in antibody tests and correlation with clinical findings

Abstract

Objectives Anti-myelin-associated glycoprotein (MAG) antibody is associated with clinically heterogeneous polyneuropathies. Our purpose was to compare neuropathy phenotypes identified by different anti-MAG tests' results. Methods Cohort study: Sera from 40 neuropathy anti-MAG EIA positive patients were tested for anti-MAG by Western blot (WB), for anti-peripheral nerve myelin (PNM) on monkey nerve by immunofluorescence assay (IFA), and for anti-HNK1 on rat CNS slices by IFA. Anti-sulfatide antibodies, for comparison, were also tested by EIA. Results Among 40 anti-MAG EIA positive sera, 85% also had anti-PNM IFA reactivity and 67.5% bind HNK1 on rat CNS. Anti-HNK1 positive patients had the classical predominantly distal acquired demyelinating symmetric (DADS) neuropathy with a benign course, while anti-PNM positive but anti-HNK1 negative patients had predominantly axonal neuropathy with a high frequency of anti-sulfatide reactivity and the worst long-term prognosis. Anti-MAG EIA positive patients without anti-PNM or anti-HNK1 IFA reactivity had a CIDP-like polyneuropathy. Conclusion Different methods to test for anti-MAG antibodies identify different clinical and electrophysiological findings, as well as long-term outcome. HNK1 reactivity is the strongest marker of DADS.

Molecular Mimicry of SARS-CoV-2 Spike Protein in the Nervous System: A Bioinformatics Approach

“…An approach to study the potential effect of antibodies on these proteins is based on the manifestations of IgM monoclonal gammopathy (IgMMG), in which IgM antibodies are directed against the post-translational modification mediated by GlcUAT-P (B3GA1_HUMAN) (present in phosphacan, MAG, and L1) [48] , [49] , [50] . This study focused on one hexapeptide and four pentapeptides in phosphacan and one pentapeptide in MAG, which are similar to those in SP and not adjacent to this epitope.…”

“…This study focused on one hexapeptide and four pentapeptides in phosphacan and one pentapeptide in MAG, which are similar to those in SP and not adjacent to this epitope. They are exposed in the antibody-accessible extracellular domains, yielding neo-epitopes of [48] , [51] . MAG is particularly important as it is associated with a large number of GoMYA biological processes involved in myelination and is also related to axons through key myelin components in the PNS and CNS.…”

A diagnostic score for anti‐myelin‐associated‐glycoprotein neuropathy or chronic inflammatory demyelinating polyradiculoneuropathy in patients with anti‐myelin‐associated‐glycoprotein antibody

“…To establish a score that might help in distinguishing anti-MAG neuropathy from CIDP, lists of clinical and electrophysiological features that are more likely to be present in anti-MAG neuropathy (see below) [4][5][6][7][8]13] and features that are more often encountered in CIDP and that are not part of the anti-MAG neuropathy typical phenotype were arbitrarily selected from the literature [9,13]. There is agreement in the literature on the clinical definition of typical anti-MAG neuropathy, which is described as a distal, chronic, slowly progressive, symmetric, predominantly sensory polyneuropathy, with ataxia, relatively mild or no weakness, and often upper limb tremor [1,[4][5][6][7][8][11][12][13]. Nerve conduction studies in patients with typical anti-MAG neuropathy may reveal specific electrophysiological features which can help to distinguish it from CIDP, typically uniform symmetrical and predominantly distal reduced conduction velocity (TLI < 0.25) without conduction block [1,[4][5][6][7][8][11][12][13].…”

“…There is agreement in the literature on the clinical definition of typical anti-MAG neuropathy, which is described as a distal, chronic, slowly progressive, symmetric, predominantly sensory polyneuropathy, with ataxia, relatively mild or no weakness, and often upper limb tremor [1,[4][5][6][7][8][11][12][13]. Nerve conduction studies in patients with typical anti-MAG neuropathy may reveal specific electrophysiological features which can help to distinguish it from CIDP, typically uniform symmetrical and predominantly distal reduced conduction velocity (TLI < 0.25) without conduction block [1,[4][5][6][7][8][11][12][13]. Four features (three clinical and one electrophysiological) supportive of the diagnosis of anti-MAG neuropathy were therefore arbitrarily chosen (Table 1).…”

“…It is still unclear whether these atypical phenotypes are part of the spectrum of anti-MAG neuropathy or represent false-positive patients with different neuropathies. Several studies failed to find an anti-MAG antibody titer cut-off able to distinguish the two groups of patients [5][6][7][8].…”