AIMP1 Protein May Be Promising Biomarker for NMOSD, Study Shows

High levels of inflammatory protein in blood linked to worse disability

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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People with neuromyelitis optica spectrum disorder (NMOSD) have elevated levels of the pro-inflammatory protein AIMP1 in the bloodstream, and higher levels seem to correlate with worse disability, a study showed.

These AIMP1 levels dropped markedly after anti-inflammatory therapy, but still remained higher among patients in remission than in people without NMOSD.

The findings suggest that AIMP1 might be involved in NMOSD development, the researchers noted, and bloodstream levels of this protein appear to be a promising predictor of NMOSD severity and an indicator of treatment effectiveness.

The biomarker study, “Secreted aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1) is a promising predictor for the severity of acute AQP4-IgG positive neuromyelitis optica spectrum disorder,” was published in the journal Multiple Sclerosis and Related Disorders.

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This illustration shows damage to the myelin sheath that surrounds and protects nerve fibers.

Levels of 3 Inflammatory Biomarkers Linked to Worse Disease in NMOSD

AIMP1 levels may predict treatment effectiveness

In NMOSD, self-reactive antibodies target and damage astrocytes, cells of the nervous system that help regulate and support nerve cells. The autoimmune condition is marked by inflammation that mainly affects the spinal cord and the optic nerve, which sends and receives signals from the eye.

Emerging evidence suggests that an immune regulatory protein called aminoacyl-tRNA synthetase complex interacting with multifunctional protein-1 — dubbed AIMP1 — participates in both harmful inflammation and damage to the blood-brain barrier. That highly selective membrane regulates which substances from the blood are able to reach the brain and spinal cord.

AIMP1 has shown potential as a bloodstream marker of disease severity in other autoimmune conditions, such as rheumatoid arthritis, lupus, and ANCA-associated vasculitis. Yet its utility in NMOSD has not been addressed.

To learn more, researchers in China collected blood samples from 94 NMOSD patients who tested positive for self-reactive antibodies against aquaporin-4 (AQP4-IgG), a water transport protein on the surface of astrocytes. The patients’ mean age was 46.5, and most (92.6%) were women.

Among the participants, 25.5% had inflammation of the optic nerve (optic neuritis), 37.2% had spinal cord inflammation (acute myelitis), and 29.8% had both. A total of 69 were in an acute disease phase, defined as current symptomatic activity of fewer than 30 days, while 25 were in remission, with relief of symptoms lasting more than 30 days.

Of those in the acute phase, 21 received intravenous (into-the-vein) methylprednisolone (IVMP) pulse therapy, in which high doses of anti-inflammatory medicine are delivered intermittently into the bloodstream to reduce side effects. Remission patients were treated with various immunosuppressants.

Neurological disability was assessed using the Expanded Disability Status Scale (EDSS), in which scores up to 3.5 are considered mild disability, and scores of 4 or higher reflect moderate-to-severe disability. A group of 33 gender- and age-matched healthy individuals were included as controls.

Results revealed that the mean AIMP1 level in the bloodstream across all NMOSD participants was significantly higher than in controls — 34.7 vs. 17.4 picograms per mL of blood (pg/mL).

Before IVMP therapy, AIMP1 levels reached a mean of 45.4 pg/mL, but significantly dropped to a mean of 14.3 pg/mL after treatment. Further, AIMP1 levels in remission patients were significantly lower (33.8 pg/mL) than in those in the acute phase, but were still higher than those found in controls.

Significantly higher AIMP1 levels also were found in acute patients with moderate-to-severe disability than in those with mild disability. Still, acute patients with mild disability had elevated levels of AIMP1 compared with controls. Nine of 31 acute patients (29%) showed evidence of blood-brain barrier impairment.

Prediction analysis estimated that 31.2 pg/mL of AIMP1 in the bloodstream of NMOSD patients was the optimal cutoff value to predict acute NMOSD before IVMP therapy. A level of 49.6 pg/mL predicted acute NMOSD with moderate-to-severe disability.

When the 49.6 pg/mL cutoff value was applied, the proportion of patients with acute moderate-to-severe NMOSD in the group with AIMP1 levels below the cutoff was 30%, while 88.9% of those with AIMP1 above the cutoff had moderate-to-severe disability levels.

Finally, after adjusting for influencing factors, statistical calculations showed an AIMP1 level above 49.6 pg/mL was the only independent predictor for EDSS severity in NMOSD.

“AIMP1 may be involved in the pathogenesis [development] of AQP4-IgG-[positive] NMOSD disease and predict the disease activity, severity, or effect of treatment in patients with NMOSD,” the researchers concluded, adding, “Further studies should be performed to reveal the precise mechanisms of AQP4-IgG-[positive] NMOSD.”