December
Autoantibody to MOG suggests two distinct clinical subtypes of NMOSD
Yaping Yan 2 3
Yujing Li 2 3
Ying Fu 2 3
Li Yang 2 3
Lei Su 2 3
Kaibin Shi 2 3
Minshu Li 2 3
Qiang Liu 1 2 3
Aimee Borazanci 1 2
Yaou Liu 2 3
Yong He 0 2
Jeffrey L Bennett 2 4
Timothy L Vollmer 2 4
Fu-Dong Shi 1 2 3
0 State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University , Beijing 100875 , China
1 Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center , Phoenix 85013 , USA
2 Yan , Y., Li, Y., Fu, Y., Yang, L., Su, L., Shi, K., Li, M., Liu, Q., Borazanci, A., Liu, Y., He, Y., Bennet, J.L., Vollmer, T.L., and Shi, F.D. (2016). Autoantibody to MOG suggests two distinct clinical subtypes of NMOSD. Sci China Life Sci 59 , 1270-1281. doi: 10.1007/s11427-015-4997-y
3 Departments of Neurology and Immunology, Tianjin Neurological Institute, Tianjin Medical University General Hospital , Tianjin 300052 , China
4 Department of Neurology, University of Colorado School of Medicine , Aurora 80045 , USA
We characterized a unique group of patients with neuromyelitis optica spectrum disorder (NMOSD) who carried autoantibodies of aquaporin-4 (AQP4) and myelin-oligodendrocyte glycoprotein (MOG). Among the 125 NMOSD patients, 10 (8.0%) were AQP4- and MOG-ab double positive, and 14 (11.2%) were MOG-ab single positive. The double-positive patients had a multiphase disease course with a high annual relapse rate (P=0.0431), and severe residual disability (P<0.0001). Of the double-positive patients, 70% had MS-like brain lesions, more severe edematous, multifocal regions on spinal magnetic resonance imaging (MRI), pronounced decreases of retinal nerve fiber layer thickness and atrophy of optic nerves. In contrast, patients with only MOG-ab had a higher ratio of monophasic disease course and mild residual disability. Spinal cord MRI illustrated multifocal cord lesions with mild edema, and brain MRIs showed more lesions around lateral ventricles. NMOSD patients carrying both autoantibodies to AQP4 and MOG existed and exhibited combined features of prototypic NMO and relapsing-remitting form of MS, whereas NMOSD with antibodies to MOG only exhibited an “intermediate” phenotype between NMOSD and MS. Our study suggests that antibodies against MOG might be pathogenic in NMOSD patients and that determination of anti-MOG antibodies maybe instructive for management of NMOSD patients.
MOG antibody; AQP4 antibody; neuromyelitis optica spectrum disorder; phenotype
INTRODUCTION
Damage to astrocytes mediated by aquaporin-4 antibody
(AQP4-ab) has been implicated as the cause of
neuromyelitis optica spectrum disorder (NMOSD) (Lennon et al., 2005;
Ratelade et al., 2012; Saadoun et al., 2010). Despite using
*Corresponding author (email: )
**Corresponding author (email:
[email protected])
the best available assays, 10%–30% of patients with NMO
and NMOSD still test negative for AQP4-ab (Granieri et al.,
2012; Papadopoulos and Verkman, 2012; Waters et al.,
2012). This suggests that other autoantigens might exist in
AQP4-ab negative patients and drive the disease progress.
Current clinical practices, however, do not distinguish
AQP4-ab-positive from -negative NMOSD patients.
Nevertheless, published literature has suggested that these two
groups of patients may have distinctive clinical features
© The Author(s) 2016. This article is published with open access at link.springer.com
(Jarius et al., 2012; Jiao et al., 2014; Kitley et al., 2013).
Importantly, we do not know whether both groups would
respond similarly to disease modifying therapies. Thus, the
identification of disease markers, including additional
autoantibodies, and their roles in relevant pathophysiological
processes would be instructive in diagnosis and
management of these NMOSD patients.
Myelin antigens such as myelin oligodendrocyte
glycoprotein (MOG) may not only be targeted secondarily in late
stage of NMOSD, but also serve as autoantigens driving
immune response in NMOSD, particularly in AQP4
antibody negative patients. The presence of antibodies against
MOG revealed in several recent studies suggests that this
could be the case (Kitley et al., 2014; Kitley et al., 2012;
Mader et al., 2011; Rostasy et al., 2013; Sato et al., 2014;
Tanaka and Tanaka, 2014). Although MOG autoantibodies
(MOG-ab) were identified in NMOSD and later confirmed
in six independent studies (Kitley et al., 2014; Kitley et al.,
2012; Mader et al., 2011; Rostasy et al., 2013; Sato et al.,
2014; Tanaka and Tanaka, 2014), whether NMOSD patients
can carry antibodies to both AQP4 and MOG remains
controversial (Kezuka et al., 2012; Kitley et al., 2014;
Weinshenker and Wingerchuk, 2014; Woodhall et al.,
2013). If so, do they exhibit any unique clinical
characteristics? In this study, we used highly sensitive
fluorescenceactivated cell sorting (FACS) analysis methods (Reindl et
al., 2013; Zhou et al., 2006) and identifie (...truncated)