Neuromyelitis optica (NMO) is a kind of demyelinating disorder that preferentially affects the optic nerves and spinal cord and results in permanent vision loss. NMO pathogenesis is thought to involve binding of anti-aquaporin-4 (AQP4) auto-antibodies to astrocytes, which causes complement-dependent cytotoxicity (CDC) and downstream inflammation leading to oligodendrocyte and neuronal injury. Vasculocentric deposition of activated complement is a prominent feature of NMO pathology. In recent years, a number of groups have found complements play an important role in the pathogenesis of NMO, and basic researches in NMO therapy due to its specificity and uniformity. Its inhibition would protect against proteins in the classical complement pathway so that cure the disease. This review will expound the the role of complement signaling pathway in the pathogenesis of NMO, and provide reference for a more in-depth understanding and clinical treatments of NMO.
Objective To observe the correlation of serum aquaporin 4 (AQP4) antibodies and condition and visual prognosis in patients with severe neuromyelitis optica spectral disorders (NMOSD). Methods Fifty NMOSD patients with visual acuity of 20/200 or worse in at least one eye were enrolled in this retrospective analysis. There were 12 males and 38 females. The age ranged from 17 to 65 years, with the mean of (39.86±2.02) years. The patients were divided into two groups according to the serum AQP4-IgG status. The ophthalmologic examination, serum anti-nuclear antibodies (ANA), myelin oligodendrocyte glycoprotein (MOG) antibody detection and vision prognosis were compared and analyzed. Glucocorticoid therapy was delivered to 46 patients who were within 1 month of onset. The visual acuity of the patients after treatment was divided into complete recovery, partial recovery, stabilization and reduction, and the visual acuity of the two groups were analyzed. Results Among 50 patients, there were 30 (60%) seropositive patients (positive group), 20 (40%) seronegative patients (negative group). The positive group had significantly higher ratio of female to male (P=0.004), and more binocular optic neuritis (ON) (P=0.010) compared with the negative group. More recurrence ON were also found in the positive group, but without statistic difference between two groups (P=0.167). There was no difference of age, course, and vision damage degrees and abnormal orbital MRI scanning between two groups (P＞0.05). Among 24 patients who underwent serum ANA detection in the positive group, 8 patients were positive. All of 18 patients who underwent serum ANA detection in the negative group were negative. The difference of the ratio of serum ANA positive patients between two groups was significant (P=0.030). Serum MOG antibody detection in the positive group was negative (0/10). Sixteen patients who underwent MOG antibody detection in negative group, 4 patients were positive. After treatment, there were 23.3%, 23.3%, 53.3% patients with vision of complete recovery, partial recovery and reduction in the positive group; 25.0%, 30.0%, 25.0% patients with vision of complete recovery, partial recovery and reduction in the negative group, respectively. There was no difference in proportion of vision with complete recovery and partial recovery between two groups (P=0.163, 0.607), but significant difference was observed in proportion of vision with stabilization and reduction between two groups (P=0.021, 0.048). Conclusions The positive serum AQP4 antibody is common in patients with severe NMOSD. The patients with AQP4 antibody in the serum are more likely combined with immunological serological markers and poor vision prognosis.
ObjectiveTo observe the thickness of per-papillary retinal fiber layer (pRNFL) and structural changes of inner macular segmented layers in optic neuritis (ON) patients with positive aquaporin-4 antibody[AQP4-Ab(+)]. Methods60 ON patients (84 eyes) including 30 of AQP4-Ab(+) ON patients (42 eyes) and AQP4-Ab(-) ON patients (42 eyes), and 40 age-gender matched health controls(80 eyes) were recruited in present study. There was no statistical significance in gender (χ2=0.568) and age (χ2=1.472) between the three groups (P > 0.05). There was no statistical significance in the percentage of different course (χ2=0.000) and logMAR best corrected visual acuity (Z=-1.492) between AQP4-Ab(+)ON and AQP4-Ab(-)ON group (P=1.000, 0.136). All subjects were examined by Spectralis-OCT. The thickness of per-papillary, nasal, nasal lower, temporal lower, temporal, temporal upper, nasal upper and papillomacular bundle (PMB) were analyzed as well as nasal pRNFL/temporal pRNFL (N/T). The macular area was divided into three concentric circles which including central region with 1 mm diameter, inner area with > 1 mm but≤3 mm diameter, and outer ring area with > 3 mm but≤6 mm diameter. The macular volume in each partition and volume in macular RNFL (mRNFL), macular ganglion cell layer (mRGCL), macular inner plexiform layer (mIPL) and macular inner nuclear layer (mINL) were analyzed. ResultsCompared to HC group, the thickness of pRNFL, every quadrants and PMB were decreased significantly in ON group (P=0.000); the macular volume and the volume of mRNFL, mRGCL, mIPL were also decreased significantly in ON group (P=0.000); but there was no statistical difference in mINL volume between two groups (P=0.700). Compared to AQP4-Ab(-)ON group, the thickness of nasal and nasal lower were decreased significantly in AQP4-Ab(+)ON group (P=0.010, 0.000); the macular and mIPL volume were also decreased significantly in AQP4-Ab(+)ON group (P=0.038, 0.033); the thickness of inferior, superior and inferior mIPL in outer ring area and nasal mRNFL in inner area were decreased significantly in AQP4-Ab(+)ON group (P < 0.05). ConclusionsCompared to AQP4-Ab(-)ON patients, the pRNFL thickness and mIPL volume decreased in AQP4-Ab(+)ON patients. The thinner pRNFL area is mainly located in nasal, nasal lower quadrants, and inferior, superior mIPL.