Three novel antibodies may lead to the early diagnosis of Sjogren’s syndrome

Reviewed by Vatinee Y. Bunya, MD

Take-home message: More information is needed about patients who test positive for one or more of three novel antibodies found to be correlated with early stages of Sjögren’s syndrome in a mouse model. Results of lip biopsies and other tests should also be considered because testing for the novel antibodies is not part of the current diagnostic criteria for Sjögren’s syndrome.

Philadelphia-Too little is known about the correlation among three novel antibodies associated with Sjögren’s syndrome in an animal model and the signs and symptoms of the disease. While better diagnostic tools are needed, at this point the test might be more useful in screening dry eye patients who are suspected of having Sjögren’s than in establishing a definitive diagnosis.

Read more at: Sjögren's Syndrome Resource Center

“There’s definitely a great need for earlier diagnosis of Sjögren’s syndrome. It continues to be underdiagnosed, with many patients going years before a diagnosis of the condition,” says Vatinee Y. Bunya, MD, co-director, Penn Dry Eye & Ocular Surface Center, Scheie Eye Institute, and assistant professor of ophthalmology at the Scheie Eye Institute, University of Pennsylvania.

“The current antibodies that are used to diagnose Sjögren’s syndrome could use some improvement,” Dr. Bunya said, citing their low specificity and sensitivity. “Twenty to 30 percent of the patients with established Sjögren’s syndrome can test negative for the traditional antibodies (SSA, SSB, rheumatoid factor, and anti-nuclear antibody). That means that we’re still potentially missing the diagnosis in a good proportion of patients.”

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Dr. Bunya and colleagues have begun to use an in-office blood test that detects three new antibodies that may aid in the early diagnosis of Sjögren’s syndrome (Sjö, Nicox/Immco Diagnostics) and conducted a study to better understand its clinical utility. The antibodies-secretory protein 1 (SP-1), carbonic anhydrase-6 (CA-6), and parotid secretory protein (PSP)-were identified in a mouse model of Sjögren’s.

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“In the mouse model, it appears that the antibodies may correlate with an earlier stage of Sjögren’s, and it was intriguing to think that perhaps this could be a useful screening tool, especially with dry eye patients,” Dr. Bunya says. “Approximately 10 percent of dry eye patients presenting to the office at a tertiary care center have Sjögren’s syndrome. But because dry eye is such a highly prevalent condition, it’s very difficult to know which patients may have Sjögren’s, and it’s not practical to work up all dry eye patients because there’s so many of them.”

Correlating antibodies to Sjögren’s patients

Corrleating antibodies to Sjögren’s patients

The investigators conducted a retrospective chart review to determine the prevalence of the novel antibodies in dry eye patients. “We also wanted to look at some of the symptoms and the reasons that they initially were tested for these novel antibodies,” Dr. Bunya says. 

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The review included the data on 68 patients with suspicion for the disease who were tested at regularly scheduled visits. Data on ocular surface staining, xerostomia (dry mouth), and arthralgias and myalgia were gathered and compared among novel antibody positive (Ab+) and novel antibody negative (Ab-) populations.    

The preliminary results showed that 22 of the 68 patients (32.4 percent) were positive for novel antibodies; CA-6 was the most common, found in 16 patients (23.5 percent). SP-1 was found in 8 patients (11.8 percent) and PSP in 7 patients (10.3 percent). One patient tested positive for both CA-6 and PSP and two for both PSP and SP-1; two patients tested positive for all three antibodies.

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The data also showed that the most common reason for performing the novel antibody testing, reported in 54.5 percent of cases, was that patients were refractory to dry eye treatment, on average having had symptoms for about five years. One third of patients were tested because of reported xerostomia, and about one fourth because of lissamine green staining greater than 2/6 in at least one eye.

Positive result correlations

Analysis of correlations between the presence of novel antibodies and the patients’ signs and symptoms indicated that patients who tested positive had higher average lissamine green staining grades and were more likely to complain of common symptoms of Sjögren’s. Among the patients who were positive for one or more of the antibodies, four of eight had a positive lip biopsy, five of 12 (41.7 percent) met American-European Consensus Criteria for Sjögren’s, five of 13 (35.5 percent) met Sjögren’s International Clinical Collaborative Alliance criteria (SICCA, provisionally endorsed by the American College of Rheumatology), and two of nine (22.2 percent) had a positive nuclear salivary scan.

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“There are some caveats to interpreting our results,” Dr. Bunya says. “We’re in the process of following up with these patients to see how many of them reached a final diagnosis of  “This warrants further study because having better antibody markers for early disease is definitely needed. However, it’s still not very clear at this point what a positive result means,” she says.

Dr. Bunya also says that she and her colleagues have begun to see patients referred from other sites who were told that they have Sjögren’s syndrome based on the results of this test. However, these antibodies are not yet part of the diagnostic criteria, and this may be causing confusion and false positive diagnoses.

When patients at the Scheie Eye Institute test positive for one of the novel antibodies, they are referred to the rheumatology department for a full Sjögren’s work-up. In this way, at this time the novel antibody test could be useful as a screening tool, providing guidance for referral rather than being the basis for a formal diagnosis, Dr. Bunya says.

A poster on this study was presented at the 2015 meeting of the Association for Research in Vision and Ophthalmology.

Vatinee Y. Bunya, MD

vatinee.Bunya@uphs.upenn.edu

Disclosure: Dr. Bunya receives support from the National Eye Institute.