Objective: To investigate that how the effect of rheumatic immune antibodies on clinical manifestation and cerebrospinal fluid characteristics of neuromyelitis optic spectrum disorders (NMOSD). Methods: All 35 patients with NMOSD in the Second Hospital, Cheeloo College of Medicine, Shandong University from 2017 to 2019 were retrospectively reviewed. All patients underwent examination of serum ANA, dsDNA, SS-A, SS-B，Ro-52 , AMA M2, Jo-1, PM-Scl, Scl-70, Sm and et al. 6 positive-autoantibody patients are compared with 29 negative-autoantibody patients in gender, onset age, duration, number of attacks, EDSS, initial presentation (on, spinal cord or brain), CSF WBC, protein, Oligoclonal band and MBP. Results: The 6 NMOSD patients with all AQP4-IgG positive had positive autoantibodies (17.1%), with no diagnose as CTD. The frequency of SSA in the positive group was 50%, while Ro-52 was 75%, AMA-M2 was 33%, ANCA-PR3 was 17%, and AHA was 17%. They were significantly higher in NMOSD patients with auto-immune antibodies positive than those without auto antibodies (P<0.05). EDSS scores were positively correlated with two groups (NMOSD with or without auto antibodies). The positive group had much more EDSS scores than the negative group. The number of CSF cells in positive group was basically in normal range, median was 2.5x106. Median of CSF protein was 866mg/L, which was much higher than negative group. Conclusions: NMOSD patients with positive autoantibodies tends to be more frequent in the patients with AQP4-IgG, who have more severe intrathecal autoimmune inflammatory and disability. So they might need more intensive treatment in the future.