Blood test for natural killer cells could improve NMOSD diagnosis: Study
Impaired signaling between NK and B-cells likely contribute to disease
Written by |
Measuring the blood levels of natural killer (NK) cells, a type of immune cell, may serve as a diagnostic biomarker for neuromyelitis optica spectrum disorder (NMOSD), a study showed.
Blood tests consistently showed significantly lower NK cell proportions and counts in NMOSD patients than in healthy individuals and in those with other nervous system diseases.
Experiments also suggested that altered gene activity within NK cells and impaired signaling between NK cells and B-cells, the immune cells that produce NMOSD-driving antibodies, likely contribute to the disease.
“Our findings position NK cell reduction and dysfunction as central features of NMOSD [development] and establish NK cell proportion and gene activity as potential biomarkers for diagnosis, differential diagnosis, and disease progression,” the scientists wrote.
The study, “Natural killer cell reduction and dysfunction define a pathogenic and diagnostic axis in neuromyelitis optica spectrum disorder,” was published in the Journal of Neuroinflammation.
Natural killer cells part of body’s first line of defense
NMOSD is characterized by inflammation and damage to the spinal cord and optic nerves, which carry visual signals from the eyes to the brain. This can result in symptoms such as muscle weakness and vision problems.
Most NMOSD cases are caused by self-reactive antibodies targeting AQP4, a protein highly present on astrocytes, which support cells in the nervous system. The resulting immune response drives astrocyte loss, myelin damage (the protective coating on nerve fibers), and nerve cell death.
“There is an urgent need for novel, reliable, complementary, and readily available biomarkers to improve diagnosis … in NMOSD” and to provide differentiation from related diseases, including multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), the researchers wrote.
NK cells are part of the innate immune system, the body’s first line of defense, and “have been increasingly implicated in NMOSD [development],” the researchers wrote. However, the precise role of NK cells in NMOSD is not fully understood, particularly how they interact with immune B-cells, which produce antibodies, including those targeting AQP4.
No relationship found between NK cell changes and NMOSD severity
To learn more, a team of researchers collected blood samples from 83 adults with NMOSD and 129 healthy individuals who served as a control group. Participants were divided into a discovery set (31 patients and 31 age- and sex-matched controls) and a validation set (52 patients and 98 controls).
Analyses of various immune cell types showed clear differences between NMOSD patients and healthy controls.
In the discovery set, patients had significantly lower median proportions of NK cells (9.35% vs. 16.05%) and absolute NK cell counts (106 cells vs. 285 cells). At the same time, the proportion of B-cells was significantly higher in patients (17.58% vs. 11.2%). These differences were confirmed in the validation set.
These NK cell measures showed good performance at distinguishing NMOSD patients from healthy controls, as reflected by area under the curve (AUC) values generally above 0.8 in the discovery and validation sets. AUC ranges from zero to one, and the higher the AUC value, the better the discriminative potential.
Still, no relationship was found between NK cell changes and NMOSD severity, as measured by the Expanded Disability Status Scale.
Our findings establish NK cell reduction and dysfunction as central features of NMOSD [immune mechanisms]. Impaired NK-B cell crosstalk through [IFN-gamma] may play a mechanistic role in disease progression, offering new avenues for therapeutic targeting.
Monitoring immune cells across the different stages of NMOSD, including the acute phase (active disease), post-treatment phase, and remission, revealed persistent changes in NK cells.
NK cell proportion remained significantly lower in patients than in healthy controls during both the acute and post-treatment phases (1.97 % vs. 14.82%). Although NK cell proportion increased during remission, they did not reach levels seen in healthy individuals, “suggesting that NK% may reflect disease activity to some extent,” the researchers wrote.
B-cell proportion increased compared with healthy controls during the acute and post-treatment phases, then decreased significantly during remission. This decrease is consistent with the effects of therapies that reduce B-cells, the team noted.
Researchers also assessed whether NK cell measures could distinguish NMOSD from other nervous system diseases, including MS, MOGAD, autoimmune encephalitis, and viral encephalitis. Statistical analyses adjusted for age and sex showed that NK cell proportion in NMOSD patients was significantly lower than in people with MS (9.27% vs. 11.28%) and autoimmune encephalitis (9.27% vs. 13.09%).
NK cell counts were also significantly lower compared with MS (50 cells vs. 168 cells) and MOGAD (50 vs. 124 cells). No significant differences were found relative to viral encephalitis. NK cell measures also showed “considerable AUC values” to distinguish NMOSD from these conditions, the team wrote.
Further analyses showed altered gene activity patterns in NK cells affecting the production of immune signaling proteins, immune regulation, and cell movement. In addition, signaling between NK cells and B-cells via the immune signaling protein IFN-gamma was reduced, likely contributing to disease-driving B-cell activation.
“Our findings establish NK cell reduction and dysfunction as central features of NMOSD [immune mechanisms],” the team concluded. “Impaired NK-B cell crosstalk through [IFN-gamma] may play a mechanistic role in disease progression, offering new avenues for therapeutic targeting.”
