OBJECTIVE: To investigate the rheumatic antibodies on characteristics of neuromyelitis optic spectrum disorders. METHODS: All the patients were tested for AQP4-IgG. There were three groups, AQP4+NMOSD, AQP4-NMOSD and control group. MRI was performed. Clinical characteristics, including sex, age, disease duration, the number and type of relapse, autoantibodies, and MRI, OCT results and the scores obtained from EDSS at the time of attack and remission were prospectively recorded. Patients and controls underwent peripapillary RNFL and macular volume OCT scanning. RESULTS: In AQP4+ NMOSD patients with optic neuritis (ON), significant associations were identified between various antibodies and OCT parameters. Specifically, INF110 was significantly correlated with dsDNA (r = 0.384, p = 0.023), FT was associated with AHA (r = -0.416, p = 0.015), and optic disc area showed a strong negative correlation with AMA M2 (r = -0.562, p <
0.001). For AQP4-NMOSD individuals, TMP 30 showed a significant relationship with PM-Scl (r = -0.410, p = 0.027), nRNP (r = 0.622, p <
0.001), AHA (r = 0.701, p <
0.001), p-ANCA (r = -0.435, p = 0.018), c-ANCA (r = -0.428, p = 0.021), and CCP (r = -0.428, p = 0.021). SUP 28 was correlated with PCNA (r = 0.426, p = 0.021), INF 110 with nRNP (r = 0.630, p <
0.001) and AHA (r = 0.706, p <
0.001), TMV with nRNP (r = -0.650, p <
0.001) and AHA (r = -0.708, p <
0.001), and FT with nRNP (r = -0.378, p = 0.043) and AHA (r = -0.464, p = 0.011). CONCLUSIONS: Rheumatic antibodies may be as biomarker to induce the severe worsening of development of NMOSD patients.