https://journals.sagepub.com/doi/full/1 ... 5231199819
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.
https://proceedings.science/bctrims-202 ... li?lang=en
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.
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).
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.