Neutrophils are the most abundant cell type in the innate immune system and are associated with the pathogenesis of NMOSD. [11,12] Studies on animal models of experimental autoimmune encephalomyelitis have shown that the reduction in neutrophils may delay disease progression. Neutrophils may play an important role in the pathogenesis of experimental autoimmune encephalomyelitis by producing cytokines, damaging the blood-brain barrier, and promoting inflammation in the brain parenchyma. [13] It is now well established that neutrophils are the main inflammatory cells involved in early pathogenesis in models of NMOSD. [14] Inflammatory cells infiltrating the lesions in NMOSD mainly include neutrophils, macrophages, and eosinophils, with relatively few T lymphocytes. [11] During the pathogenesis of NMOSD, neutrophils are the first inflammatory cells to enter the lesion; entering may occur within a few hours after the onset of inflammation. Within 12 hours after onset, perivascular complement activation and loss of AQP4 with early myelin loss occur. In the chronic phase (seven days), there were almost no neutrophils in the lesion, and macrophages dominated and infiltrated extensively into the white matter. [11,15] In the present study, the WBC counts and absolute neutrophil counts during episodes of NMOSD were significantly higher than those in remission of NMOSD and the control group, whereas in patients with NMOSD in remission, there were no statistically significant differences compared with the controls, suggesting that neutrophils play a role during episodes of NMOSD. This finding is consistent with the pathophysiological process of NMOSD. Therefore, treatment for NMOSD should block the persistent inflammation produced by the apoptosis of neutrophils, promote the apoptosis of neutrophils, enhance the regression of inflammation, inhibit excessive tissue injury, and avoid persistent chronic inflammation. [16]
The NLR is a systemic inflammatory marker based on routine blood tests, which are low in cost and easy to obtain. The NLR can reflect both the increase in neutrophils and the decrease in lymphocytes during the inflammatory response. The NLR has been correlated not only with some autoimmune diseases [9,17] but also with neurological disorders, such as Parkinson’s disease [18] and Alzheimer’s disease. [19] Several studies have verified that the NLR is correlated with the prognosis of diseases such as rheumatoid arthritis, [9] cancer, [20, 21] and stroke. [22]
Studies concerning NLR and NMOSD are rarely reported. Neutrophils are involved in the pathogenesis of NMOSD, [11, 13, 14] and the NLR can reflect changes in neutrophils in vivo. The present study revealed that the NLR was significantly higher in patients experiencing episodes of NMOSD than in patients in remission and controls. The change in NLR was due to an increase in the absolute neutrophil count and a decrease in the absolute lymphocyte count. Thus, it was suggested that the NLR could be used as one of the peripheral inflammatory biomarkers of disease activity in patients with NMOSD. The NLR and absolute neutrophil counts of patients with NMOSD at the attack stage were significantly higher than those of patients in remission, indicating that the inflammatory response in NMOSD onset might be more intense than that in remission, which also verified the difference in pathogenesis between the two different stages. This result suggests that the index has a moderate prediction value, indicating that the NLR might be a useful additional peripheral inflammatory biomarker in assessing disease activity in patients with NMOSD.
PLR is gaining importance as an indicator of inflammation. PLR in combination with NLR can better reflect the changes in inflammation in vivo and avoid the influence of other factors on the absolute counts of leukocyte subtypes. The present study revealed no statistically significant differences in the absolute platelet count between patients with NMOSD at the attack stage, remission stage and the controls, but the absolute lymphocyte count of patients experiencing episodes of NMOSD was significantly lower than that of patients in remission and the controls. The PLR of patients with NMOSD attack stage was significantly higher than that of the controls, which may make the decrease of absolute lymphocytes count of patients with NMOSD attack stage larger. There was a significant decrease in absolute lymphocyte count during episodes in patients with NMOSD, but there was no consistent change in PLR. There was no significant difference in PLR between the NMOSD attack stage and remission stage, but P =0.058, which was close to statistical significance. This value might be correlated with the small number of patients with NMOSD, so it would be necessary to expand the number of cases in further studies. This study investigated the sensitivity and specificity of NLR and PLR to inflammatory changes in NMOSD patients by drawing ROC curves. It was found that the changes in NLR in patients with attack stage were statistically significant compared with those in remission stage and the controls and better reflected inflammatory changes than PLR.
Drug use in patients with NMOSD may affect the WBC count, absolute neutrophil count, and absolute lymphocyte count, thereby affecting NLR and PLR. Some NMOSD patients took immunosuppressants in the onset and remission stages, and the proportion of immunosuppressants in the remission stage was significantly higher than that in the onset stage, which may partially affect NLR and PLR.
In conclusion, NLR might significantly increase in patients with NMOSD during episodes, and the increase in NLR might be correlated with inflammatory activity in NMOSD. The NLR could be used as a peripheral inflammatory biomarker of disease activity during an episode in patients with NMOSD and has some clinical applications. NLR can be a useful complement to MRI and CSF in the diagnosis of MS disease and is easier to achieve than the latter. However, the present study was a single-center study, and the number of patients enrolled was relatively small. The patients were taking different medications before relapse and after relapse, which might affect the results and have certain limitations. Further expansion is needed to increase the number of patients.