Specific Protein in Tears May Better Diagnose Sjögren’s

The amount of a protein called ATG5 in tears may pinpoint people whose dry eye symptoms are related to Sjögren’s syndrome with greater accuracy than standard diagnostic tests, a study has found.

However, ATG5’s potential as a biomarker of the disorder should be investigated further, the researchers said.

The study, “Tear ATG5 as a Potential Novel Biomarker in the Diagnosis of Sjögren Syndrome,” was published in the journal Diagnostics.

Although inflammatory signals and immune system cells are both known to contribute to the development of Sjögren’s syndrome, there is some evidence to suggest that autophagy — a mechanism used by cells to clear out damaged or unnecessary components — also plays a role.

In a recent study, scientists at Seoul University and the Catholic University of Korea found elevated levels of autophagy markers in the tears and cells of the outer eye layer of people with dry eye symptoms related to Sjögren’s syndrome, but not in dry eye patients without the condition.

One such marker was ATG5, a key autophagy protein whose levels reflect increases or decreases in autophagy. Thus, the same team set out to investigate whether ATG5 in tears might signal the presence of Sjögren’s syndrome or even discriminate it better than other tests.

Current tests largely diagnose Sjögren’s syndrome through the effect it has on patients’ tears and the outer layer of the eye. Tests include tear breakup time (TBUT), which measures the rate of tear evaporation on the eye, the Schirmer I test, which determines if the eyes produce enough tears to remain moist, and the ocular staining score (OSS), which measures damage to the eye.

Although widely used, these tests show high variability and measurement errors, leading some researchers to seek out alternatives.

To test the usefulness of ATG5 in distinguishing dry eye patients with Sjögren’s from those without the disorder, the investigators compared patients using ATG5 levels and other ocular tests.

A total of 86 participants were enrolled, including 55 Sjögren’s syndrome patients with dry eyes, and 31 people with non-Sjögren’s dry eye, who served as controls. Compared with the control group, Sjögren’s patients were generally younger (average of 50.7 vs. 55.7 years) and had more severe dry eye symptoms, as assessed by a shorter breakup time, higher OSS scores, and more conjunctival staining.

Sjögren’s patients also had significantly greater amounts of ATG5 in their tears.

Among those with Sjögren’s, ATG5 levels correlated, albeit weakly, with OSS and TBUT scores. In contrast, the researchers observed no statistically significant correlation between ATG5 and other tests among controls.

In a final analysis, the investigators found that ATG5 had a much greater accuracy (98.4%) at distinguishing Sjögren’s from non-Sjögren’s cases than the other eye tests — whose accuracy ranged from 81.7% to 50.8%.

When researchers used 4.0 nanogram/milliliter/microgram as a cut-off value for discriminating Sjögren’s from non-Sjögren’s cases, tear ATG5 also a sensitivity (true-positive rate) of 94.6% and specificity (true-negative rate) of 93.6%. These were both much higher than the sensitivity and specificity obtained with other eye tests.

“The diagnostic performance of tear ATG5 far exceeds that of other ocular tests that are currently used as diagnostic criteria” for Sjögren’s syndrome, the researchers wrote.