Double-negative neuromyelitis optica spectrum disorder

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Double-negative neuromyelitis optica spectrum disorder

https://journals.sagepub.com/doi/full/1 ... 5231199819

Abstract

Most patients with neuromyelitis optica spectrum disorders (NMOSD) test positive for aquaporin-4 antibody (AQP4-IgG) or myelin oligodendrocyte glycoprotein antibodies (MOG-IgG).

Those who are negative are termed double-negative (DN) NMOSD and may constitute a diagnostic and therapeutic challenge.

DN NMOSD is a syndrome rather than a single disease, ranging from a (postinfectious) monophasic illness to a more chronic syndrome that can be indistinguishable from AQP4-IgG+ NMOSD or develop into other mimics such as multiple sclerosis. Thus, underlying disease mechanisms are likely to be heterogeneous.

This topical review aims to (1) reappraise antibody-negative NMOSD definition as it has changed over time with the development of the AQP4 and MOG-IgG assays; (2) outline clinical characteristics and the pathophysiological nature of this rare entity by contrasting its differences and similarities with antibody-positive NMOSD; (3) summarize laboratory characteristics and magnetic resonance imaging findings of DN NMOSD; and (4) discuss the current treatment for DN NMOSD.

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MOG-IgA characterizes a subgroup of patients with central nervous system demyelination

https://proceedings.science/bctrims-202 ... li?lang=en

Abstract

Introduction:

The differential diagnosis of patients with seronegative demyelinating central nervous system (CNS) disease is challenging. In this regard, mounting evidence suggests that immunoglobulin (Ig) A plays a role in the pathogenesis of different autoimmune diseases. Yet, little is known about the presence and clinical relevance of IgA antibodies against myelin oligodendrocyte glycoprotein (MOG) in CNS demyelination.

Objective:

To investigate the frequency and associated clinical features of MOG-IgA in a cohort of patients with demyelinating CNS disease and healthy participants.

Design/Methods: We conducted an observational, retrospective, longitudinal, multicenter study measuring MOG-IgA in serum using a live cell-based assay. We included 1339 patients with neuromyelitis optica spectrum disorder (NMOSD), other CNS demyelinating diseases, and multiple sclerosis (MS), as well as healthy controls (HC).

Results:

Of included isolated MOG-IgA patients, 61% (n=11/18) were females and median age was 31.5 years (range: 3-76). Among patients double-seronegative for AQP4-IgG and MOG-IgG (n=1126/1339; 84%), isolated MOG-IgA was identified in 6% (n= 3/50) of patients with NMOSD, in 2% (n=5/228) of patients with other CNS demyelinating disease, and in 1% (n=10/848) of patients with multiple sclerosis (MS) but in none of the HC (n=0/110). The most common disease manifestation in isolated MOG-IgA seropositive patients was myelitis (65%, n=11/17), followed by more frequent brainstem syndrome (44%, n=7/16; p=0.05 [0.048]), and infrequent manifestation of ON (27%, n=4/15; p=0.02) compared to MOG-IgG patients. Among patients fulfilling 2017 McDonald criteria for MS, MOG-IgA was associated with less frequent type II oligoclonal bands (OCBs) (38%, n=3/8) compared to MOG-IgG/IgA seronegative MS patients (93%, n=325/351; p<0.0001). Further, most patients with isolated MOG-IgA presented events of demyelination after recent infection/vaccination (64%, n=7/11).

Conclusion and relevance:

We identified MOG-specific IgA in a subgroup of AQP4-/MOG-IgG double-seronegative patients, suggesting MOG-IgA as a novel diagnostic biomarker for patients with CNS demyelination.