Natural killer (NK) cells and natural killer T (NKT) cells seem to play a crucial role in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD), according to a new study published in the Journal of Neuroinflammation. They exert their activity by expressing complement receptors and CD16 after being activated and migrating to the periphery. This triggers antibody-dependent cellular cytotoxicity and the prolonged production of autoantibodies leading to an escalating autoimmune activity.

According to the authors of the study, more research is needed to better understand how immune complexes, complement, and cytokines change these cells and how they are involved in NMOSD.

Read more about the pathophysiology of NMOSD

In the present study, a team of researchers led by Michael Levy, MD, PhD, from the Department of Neurology, Massachusetts General Hospital and Harvard Medical School in Boston, MA compared the expression of CD16 on immune cells modulated by complement activity in NK cells and NKT cells in patients with NMOSD, patients with other diseases, and healthy controls.

The researchers obtained peripheral blood samples from 45 aquaporin-4 (AQP4)-positive patients with NMOSD, 18 patients with other diseases including myelin-oligodendrocyte glycoprotein associated disease (MOGAD), multiple sclerosis (MS), Crohn’s disease, neuropsychiatric systemic lupus erythematosus, rheumatoid arthritis, transverse myelitis, ankylosing spondylitis, and AQP4 negative NMOSD, and 19 healthy controls. They analyzed the expression of CD16 and complement receptors in these samples.

They found that the number of NKT cells was higher in the blood of patients with NMOSD compared to disease controls and healthy controls. However, the proportion of cells that were CD16 positive was lower

The number of NK cells was within the normal range in patients with NMOSD. However, the ratio of NK cells that were CD16 positive was also significantly lower than disease or healthy controls. 

In both types of cells obtained from patients with NMOSD, the expression of the C5 complement receptor was much higher compared to both disease and healthy controls as were the activation markers CD69 and CD83. 

Finally, the researchers reported that patients with NMOSD who had the V/V genotype of the FCGR3A gene had lower NK cell proportion with activation, and fewer CD16-expressing NKT cells compared to those with the F/F genotype.

“Our results support an immunopathogenesis model in which complement pathway activation in NK/NKT cells upregulates CD16 expression that binds to antibody/antigen complexes,” the researchers wrote. “In the context of NMOSD, these complement-sensitive cells may be responsible for the escalating autoimmune activity”.

Reference

Nishiyama S, Wright AE, Lotan I, et al. Upregulated complement receptors correlate with Fc gamma receptor 3A-positive natural killer and natural killer-T cells in neuromyelitis optica spectrum disorder. J Neuroinflammation. Published online December 12, 2022. doi:10.1186/s12974-022-02661-1