Patients with neuromyelitis optica spectrum disorder (NMOSD) exhibit increased expression of CD226 on type 1 T regulatory (Tr1) cells, according to a study published in Brain And Behavior.

The CD226 levels on Tr1 cells also tended to correlate with NMOSD severity and the expression levels would decrease following treatment with methylprednisolone and rituximab. CD226 is involved in the regulation of immune cells such as the differentiation of initial T cells and the polarization of Th1 cells.

“This study provides a new basic insight into CD226 expression pattern on Tr1 cells, which have great potential to be biomarkers for monitoring the development and treatment of NMOSD,” the study’s authors said.

Continue Reading

The study also found that overall, Tr1 and Foxp3+Treg cells were decreased in patients with NMOSD when compared to blood samples taken from healthy volunteers. The authors hypothesized that Tr1 and Treg cells might be involved in the pathogenesis of NMOSD.

Read more about NMOSD pathophysiology

On the Tr1 cells observed in patients with NMOSD, the levels of CD226 were significantly higher compared to healthy volunteers. No significant difference was observed in the CD226 levels on Foxp3+Treg cells between NMOSD and healthy controls, however.

Following treatment with 1 g of methylprednisolone and 100 mg of rituximab for 1 month, the levels of Tr1 and Treg cells became elevated. Also after treatment, the Tr1 cells expressed less CD226 while the expression on Treg cells was unchanged.

Higher levels of CD226 on Tr1 cells were found to be positively correlated with disease severity quantified through the amount of affected spinal cord segments observed on magnetic resonance imaging. Interestingly, higher levels of CD226 on Tr1 cells also had a positive correlation with Barthel Index scores.

“This study provides pivotal information to understand the mechanisms implicated in NMOSD and inspires new ideas for diagnosis and treatment of the diseases by considering the individual conditions based primarily on the CD226 expression analysis,” the authors concluded.

The data from 18 patients with NMOSD and 10 healthy volunteers were analyzed for the study between January 1, 2015, and December 31, 2018. Not all of the patients had data for each individual analysis, however.


Chen P, Wu M, Wang N, et al. Expression of CD226 is upregulated on Tr1 cells from neuromyelitis optica spectrum disorder patients. Brain Behav. Published online May 19, 2022. doi:10.1002/brb3.2623