Blood Levels of Anti-HMGB1 Antibodies May Help in Diagnosing Sjögren’s

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by Steve Bryson, PhD |

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Levels of antibodies that target the nuclear protein HMGB1 are elevated in the bloodstream of adults with Sjögren’s syndrome, a study reported.

Detecting anti-HMGB1 antibodies in the blood may support a clinical diagnosis of Sjögren’s syndrome, its researchers suggested.

The study, “Anti-HMGB1 antibody is a potential characteristic autoantibody for Sjögren’s syndrome,” was published in the journal Nature Scientific Reports.

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In Sjögren’s syndrome, the immune system mistakenly attacks the glands that produce tears and saliva, causing symptoms of dryness in the eyes and mouth, but other tissues can also be affected.

Diagnosing Sjögren’s can be challenging because the underlying cause is unknown, and its symptoms are similar to those of other conditions. As a result, no single test can confirm the presence of Sjögren’s, but rather requires a series of tests and questions.

A Sjögren’s hallmark is the presence of antinuclear autoantibodies (ANAs) in the bloodstream — self-reactive antibodies that target components of the cell nucleus, the compartment that contains a cell’s genetic information. These autoantibodies, however, are found in various autoimmune diseases.

Around 70% of people with Sjögren’s have antibodies against the nuclear protein Ro (SS-A), while approximately 45% have antibodies against the nuclear protein La (SS-B). These antibodies can also be found in patients with other autoimmune conditions, as well as healthy people.

HMGB1 is another nuclear protein that plays a key role in inflammation-related immune regulation. Studies indicate that autoantibodies against HMGB1 are present in various autoimmune diseases, but whether this protein is an immune target in Sjögren’s is unknown.

Researchers at Changhai Hospital in Shanghai, China, examined the blood of 93 adults with Sjögren’s syndrome alongside that of 96 age-matched healthy individuals. Patients’ ages ranged from 23 to 80, and 88 were female.

Blood tests showed the levels of anti-HMGB1 antibodies were significantly higher in the bloodstream of Sjögren’s patients than healthy adults (9.96 vs. 4.9 relative units per milliliter, or RU/ml, of blood).

At a cutoff value set at 8 RU/mL, the levels of anti-HMGB1 antibodies were able to discriminate people with and without Sjögren’s with a sensitivity of 64.5% and a specificity of 96.9%. Sensitivity refers to a test’s ability to correctly identify people with a condition, while specificity refers to its ability to correctly identify those without a condition.

Among the 93 Sjögren’s patients, 87 (93.5%) tested positive for antinuclear autoantibodies, and 61 (70.1%) carried anti-HMGB1 antibodies. A total of 63 (66.7%) patients tested positive for anti-SS-A antibodies, and 37 (39.8%) were positive for anti-SS-B antibodies.

In patients with anti-HMGB1 antibodies, 25 (28.7%) also had anti-SS-A and anti-SS-B antibodies, and 18 (20.7%) had anti-SS-A antibodies. Anti-HMGB1 antibodies alone were found in 18 (20.7%) patients.

Of the 26 (29.9%) people without anti-HMGB1 antibodies, 20 (23.0%) had anti-SS-A antibodies, 12 (13.8%) had anti-SS-B antibodies, and six others (6.9%) had neither.

Cellular imaging analysis demonstrated that anti-HMGB1 antibodies had a similar nuclear pattern as ANAs. To confirm these results, the team created a cell line lacking HMGB1, then added the blood serum of a Sjögren’s patient. Control cells with HMGB1 tested positive, whereas those without HMGB1 did not.

“The results of this study show that the anti-HMGB1 antibody may be one of the characteristic autoantibodies of [Sjögren’s syndrome],” the scientists concluded. “The detection of anti-HMGB1 antibody can provide laboratory evidence for clinical diagnosis of [Sjögren’s syndrome], and further improve the accuracy of [Sjögren’s syndrome] diagnosis based on the existing detection indicators.”

Further research into the role of HMGB1 in Sjögren’s syndrome “may lead to the development of new drugs or treatment strategies” for the disease, they wrote.