This article has been reviewed by Vatinee Bunya, MD, MSCE.
Adding data on new autoantibodies linked to Sjogren syndrome (SS) could improve screening for SS in patients with dry eye disease, according to a study presented at the recent annual meeting of the Association for Research in Vision and Ophthalmology.
The study, funded by the National Eye Institute, was led by Vatinee Bunya, MD, MSCE, and was presented by Kennedy Johnson, clinical research coordinator at the Scheie Eye Institute at the University of Pennsylvania in Philadelphia.
Sjogren’s syndrome is an underdiagnosed autoimmune disease in which diagnosis is often delayed for a few years, and dry eye is one of the most common symptoms of SS, Johnson explained. However, because dry eye is such a common condition, it is not possible to test for SS in all patients with dry eye, she noted.
“Because dry eye is one of the most common symptoms of the disease (SS), ophthalmologists often see these patients first and therefore are in a unique position to screen dry eye patients for Sjogren’s syndrome. Johnson said.
There are traditional antibodies to test for SS and they include Sjogren’s syndrome-related A and B antigens (SSA, SSB), antinuclear antibodies (ANA), and rheumatoid factor (RF) -related A and B antigens (RF), but Johnson noted that these traditional antibodies are not specific for SS and that they are not always found in all patients with SS.
Previous search1 who assessed dry eye patients for SS found that half of the patients required a minor salivary gland biopsy to reach a definitive diagnosis due to the lack of positive antibody tests, Johnson noted.
“We believe it is important to identify new serological biomarkers that could better characterize Sjogren syndrome and overcome the limitations of traditional antibodies,” Johnson said. “Many studies have explored new antibodies for Sjogren syndrome.”
One of those studies concluded that antibodies to salivary protein, parotid secretory protein, and carbonic anhydrase isoenzyme VI (CA-6) may be new markers of SS, Johnson said. In addition, in studies on mice, these new antibodies were detected earlier in the disease process.2
Other research has found that anti-CA6 is associated with younger age and more serious disease,3 Johnson noted. In addition, other studies have shown that the SP-1 IgM and PSP autoantibodies have an increased prevalence in patients with SS and that SP-1 may be a marker for more serious ocular surface disease.4.5
Research suggests that autoantibodies can not only help detect SS patients, but also detect SS patients with more severe disease, Johnson explained.
Bunya and her team at the Scheie Eye Institute had previously developed a screening questionnaire that included eye examination results such as tear film breakup time and conjunctiva lissamine green stain to help detect patients with dry eye. which may also have an underlying SS. The sensitivity of the algorithm was 78% and the specificity was 66%.6
Since then, the team has sought to refine the tool’s diagnostic ability and increase sensitivity and specificity by incorporating new data on autoantibodies. They launched a study that included patients with dry eye over the age of 18 without a previous diagnosis of SS or any other autoimmune disease.
They also excluded patients with a history of corneal refractive surgery, radiation therapy to the head or neck, chemotherapy, pre-existing lymphoma and patients taking topical glaucoma medication. In terms of defining SS, they used classification criteria as developed by the American College of Rheumatology and the European Rheumatism League, Johnson noted.
In addition to completing the questionnaire, study subjects also underwent an ocular surface examination, unstimulated saliva flow test, and serologic testing. A subset of subjects also underwent labial salivary gland biopsy if indicated.
Interestingly, the researchers found that the percentage of positive subjects in SP IgA, PSP IgM, and CA-VI IgM specific immunoglobulin groups was significantly higher in those with SS than in those without SS.
“We had 25.4% in the absence of Sjögren syndrome and 61.1% in the presence of Sjögren syndrome,” Johnson said, noting that the inclusion of the SP IgA, PSP IgM and CA-VI autoantibodies IgM has demonstrated an improvement in the performance of the old developed algorithm.
The study, however, needs to be conducted in a larger and more diverse population to ensure the uptake of the screening method, Johnson said.
“Our study has some limitations,” Johnson said. “Our sample size was small and only involved one center, with the majority of patients being older Caucasian women. Going forward, we would like to include additional sites and a more diverse patient population to increase the generalizability of our screening tool. Future studies may also involve the analysis of tear and saliva samples, which were collected during our study to further examine the presence of these autoantibodies and other biomarkers in patients with or without the syndrome. by Sjogren.
The probability scoring system that Johnson and his colleagues developed can be implemented using the brief series of questions alone, or combined with standard ocular surface signs and new autoantibody tests for a improved performance.
“In the future, once the algorithm is validated, it could serve as an effective screening tool to identify patients with Sjogren syndrome at a younger age, thus leading to an earlier diagnosis,” Johnson said.
- Akpek EK, Klimava A, Thorne JE, Martin D, Lekhanont K, Ostrovsky A. Assessment of patients with dry eye for the presence of underlying Sjögren syndrome. Cornea. 2009; 28 (5): 493-497.
- Shen L, Suresh L, Lindemann M, et al. New autoantibodies in Sjogren’s syndrome. Clin Immunol. 2012; 145 (3): 251-255.
- Karakus S, Baer AN, Agrawal D, Gurakar M, Massof RW, Akpek EK. Usefulness of novel autoantibodies in the diagnosis of Sjogren syndrome in patients with dry eye. Cornea. 2018; 37 (4): 405-411.
- Bunya VY, Ying G, Maguire MG et al. Prevalence of new candidate Sjogren syndrome autoantibodies in the dry eye assessment and management (DREAM) study. Cornea. 2018; 37 (11): 1425-1430.
- Bunya VY, Masaro-Giordano M, Vivino FB, et al. Prevalence of new candidate Sjogren syndrome autoantibodies in the international collaborative clinical alliance cohort of Penn Sjogren. Cornea. 2019; 38 (12): 1500-1505.
- Bunya VY, Maguire MG, Akpek EK et al. A new screening questionnaire to identify patients with dry eye with a high probability of having Sjogren’s syndrome. Cornea. 2021; 40 (2): 179-187.
Vatinée Y. Bunya, MD, MSCE
Bunya is Co-Director of the Penn Dry Eye and Ocular Surface Center and Associate Professor of Ophthalmology at the University of Pennsylvania Hospital. She indicated any proprietary interest in the subject.