Background and objectiveNeuromyelitis optica spectrum disorders (NMOSD) are chronical inflammatory demyelinating diseases of the central nervous system (CNS) and the underlying mechanism remains unclear. Several recent studies have demonstrated that T cells play a pivotal role in the pathogenesis of NMOSD.In this study, we investigated CD8+ T cell phenotypes and levels of the cytotoxic protein granzyme B (GzmB), as well as their potential clinical application in NMOSD.MethodsIn this study, 90 peripheral blood samples were collected from 59 NMOSD patients with seropositive anti-aquaporin-4 (AQP4) antibodies and 31 sex- and age-matched healthy donors (HDs). Flow cytometry was used to detect circulating levels of GzmB and CD8+ T cell subpopulations, including naïve (TN, CCD7+CD45RA+), central memory (TCM, CCD7+CD45RA-), effector memory (TEM, CCD7-CD45RA-), terminal differentiation effector memory cells (TEMRA, CCD7-CD45RA+) in both groups. The associations between GzmB levels in CD8+T cells and clinical characteristics of NMOSD were evaluated.ResultsNMOSD patients exhibited significantly decreased proportions of CD8+TN cells and increased proportions of highly differentiated CD8+T cells (TEMRA) compared with HDs. In addition, levels of GzmB in CD8+ T cells were markedly higher in NMOSD patients than in HDs. Moreover, we observed that high proportions of GzmB-expressing CD8+ T cells were more common in patients with a poor response to immunotherapies, and showed a good potential to distinguish poor responders from responders (ACU=0.89). Clinical correlation analysis indicated that high levels of GzmB in CD8+ T cells were not only related to severe disability but also significantly associated with increased serum levels of neurofilament light (NFL) and glial fibrillary acidic protein (GFAP). Multivariate linear regression analyses further suggested that GzmB expression in CD8+ T cells was predominantly associated with disability and immunotherapy effectiveness in NMOSD, independent of the sex, age, and disease phase. Transcription factor T-bet in CD8+ T cells were also significantly elevated in NMOSD and were associated with increasing number of circulating CD8+TEMRA cells and GzmB-expressing CD8+T cells.ConclusionsOur study support the involvement of GzmB-expressing CD8+ T cells in the inflammatory response in patients with NMOSD and provide a potential biomarker for disease immunotherapy effectiveness and disability progression.

No abstract

No abstract

Objective: T lymphocytes, complement, and immunoglobulin play an important role in neuromyelitis optica spectrum disorders (NMOSD). As common clinical examination indicators, they have been used as routine indicators in many hospitals, which is convenient for being carried out in clinical work, but there are few articles of guiding significance for clinical practice. The purpose of this study was to study the relationship between commonly used immune indicators and clinical characteristics in patients with NMOSD. Methods: We compared clinical characteristics and clinical immune indicators in 258 patients with NMOSD and 200 healthy controls (HCs). We used multiple linear regression to study the relationship between immunotherapy, disease phase, sex, age, AQP4-IgG, and immune indicators. In addition, lymphocyte subsets were compared before and after immunotherapy in 24 of the 258 patients. We explored the influencing factors and predictors of severe motor disability. Results: The percentages of CD3 ratio (71.4% vs. 73.8%, p = 0.013), CD4 ratio (38.8% vs. 42.2%, p < 0.001), and CD4/CD8 ratio (1.43 vs. 1.66, p < 0.001) in NMOSD patients were significantly lower than those in the HC group. In addition, complement C4 (0.177 g/L vs. 0.221 g/L, p < 0.001) and peripheral blood IgG (10.95 g/L vs. 11.80 g/L, p = 0.026) in NMOSD patients were significantly lower than those in the HC group. CD3 percentage was correlated with blood collection age and disease stage; CD8 percentage was correlated with blood collection age, disease stage, and treatment; CD4/CD8 percentage was correlated with blood collection age and treatment; complement C4 was correlated with blood collection age and sex; and IgG was correlated with disease stage and treatment. Twenty-four patients before and after treatment showed that the percentages of CD3 ratio (74.8% vs. 66.7%, p = 0.001) and CD8 ratio (32.4% vs. 26.2%, p < 0.001) after treatment in NMOSD patients were significantly increased, and the percentage of CD3 before treatment was moderately negatively correlated with ARR (r = −0.507, p = 0.011). Binary logistic regression analysis showed that peripheral blood complement C3 is a serious influencing factor for severe motor disability (EDSS score ≥ 6 points). Peripheral blood complement C3 and C4 are predictors of severe motor disability (p < 0.05). Conclusion: Our results suggest that peripheral blood T lymphocytes, C3, C4 and immunoglobulin are convenient and routine clinical indicators that are convenient for implementation in clinical work. They have certain reference values for disease staging, recurrence, drug efficacy, and motor disability. They have improved our understanding of clinical immune indicators for NMOSD patients, but whether they can be used as biomarkers for clinical prognosis remains to be further studied.

No abstract