New GPR37 blood test predicts NMOSD severity, tracks treatment
Lower protein levels associate with recent relapse, worse neurological disability
A blood test measuring levels of the GPR37 protein may help diagnose neuromyelitis optica spectrum disorder (NMOSD), assess disease severity, and monitor treatment response, according to a new study.
The GPR37 test was also able to distinguish NMOSD from multiple sclerosis (MS) and other neurological disorders.
“Our findings suggest that GPR37 may serve as a promising biomarker not only for differential diagnosis and disease severity assessment in NMOSD but also for evaluating therapeutic response,” the researchers wrote.
The study, “Serum GPR37 as a novel biomarker for disease activity, disability, and differential diagnosis in NMOSD,” was published in Clinica Chimica Acta.
Distinguishing NMOSD from multiple sclerosis
NMOSD was once grouped with MS because both conditions are characterized by an abnormal immune attack on the central nervous system (CNS; brain and spinal cord) resulting in demyelination — the loss of myelin (the fatty coating around nerve fibers).
Now, NMOSD is known as a separate condition. It mainly impacts nerve-supporting cells (astrocytes), and the spinal cord and optic nerve, which relays signals from the eyes to the brain. MS, in comparison, directly attacks the myelin sheath, affecting several brain areas in addition to the spinal cord and optic nerve.
Recent studies identified the GPR37 protein as a key regulator of the maturation of oligodendrocytes — the cells that produce myelin. The protein is essential for producing and maintaining myelin in the CNS.
In the study, a research team in China explored whether blood levels of GPR37 can be used as a biomarker to help diagnose NMOSD and monitor disease activity and treatment response.
Researchers analyzed blood samples from 144 adults with NMOSD, 132 adults with MS, and 160 controls (healthy people and those with other neurological disorders not related to myelin degeneration). All were seen at a single Chinese hospital.
Results showed blood GPR37 levels were significantly lower in people with NMOSD and MS compared with controls as a whole, as well as those with other neurological disorders, including non-demyelinating disorders.
“This suggests that [blood] GPR37 may help distinguish demyelinating from non-demyelinating disorders,” the team wrote.
Among NMOSD patients, GPR37 levels were comparable between those with and without self-reactive antibodies against AQP4, a protein mainly found in astrocytes. However, levels dropped significantly during relapses, or periods of sudden symptom worsening, compared with remission (times with no or minimal symptoms).
In contrast, blood GPR37 levels in MS patients were similar during periods of relapse or remission, and between different types of MS.
GPR37 separates NMOSD from other disorders
GPR37 levels were significantly lower in NMOSD patients compared with MS patients, suggesting that measuring this protein could help distinguish NMOSD from other neurological conditions.
Using a cutoff GPR37 level of 24.65 micrograms per mL to distinguish between NMOSD and MS, the team correctly identified 87% of NMOSD patients and ruled out 42% of those who actually had MS.
Combining blood levels of GPR37 with blood levels of commonly used markers for inflammation and nutrition allowed the discrimination of NMOSD patients from MS patients with an accuracy of 82.9%.
A similar approach differentiated between people with and without MS with 95.5% accuracy. GPR37’s diagnostic performance for MS was 85.7%.
Tracking disease severity and treatment response
Further statistical analyses in the NMOSD group showed lower GPR37 levels were independently associated with a recent relapse and worse disease severity, as assessed by the Expanded Disability Status Scale.
“This suggests that GPR37 may reflect underlying [disease] processes related to neurological disability and inflammatory burden,” the researchers wrote.
For MS patients, however, GPR37 levels did not correlate with any demographic or clinical features. Still, GPR37 was not related to the annual relapse rate within either the NMOSD or MS groups.
Regarding treatment response, GPR37 levels rose significantly from before treatment to two weeks post-treatment in NMOSD and MS patients who had acute exacerbation. This upward trend in GPR37 continued over the subsequent six months of maintenance therapy.
The researchers said GPR37 may serve as a biomarker for CNS demyelinating diseases, and aid in diagnosing NMOSD and differentiating it from other neurological disorders. They also said they found new evidence that blood GPR37 levels may reflect disease severity and activity in NMOSD.
The team noted, however, that larger, multicenter studies are needed to confirm these findings.
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