Association of Novel Sjogren’s Markers in Patients with Sjogren’s Syndrome in a Diverse Academic Cohort

Summary: Authors: Danielle Henry MBBS(1), Katelyn Kaufman DO(1) , Schartess Culpepper MD(2) (1)Internal Medicine Department, University of Miami at Holy Cross Health, Fort Lauderdale, FL, United States, (2) Rheumatology Department, University of Miami, FL, United States. Background and Objectives Sjogren’s syndrome (SS) is a heterogenous systemic inflammatory autoimmune disease characterized by sicca symptoms. It affects 0.3-1 per 1000 of the general population1. Studies suggest that novel autoantibodies or "early Sjogren’s markers,” particularly salivary protein 1 (SP1), carbonic anhydrase 6 (CA6,) and parotid specific protein (PSP) are present in early disease prior to anti-Ro and anti-La positivity. The antigen salivary gland protein 1 is highly expressed in the submandibular and lacrimal glands and expressed at lower levels in the parotid gland2. The antigen carbonic anhydrase 6 is highly expressed in acinar cells of the submandibular and parotid glands and renal tubules3. The antigen parotid secretory protein is expressed in high levels in the parotid glands but can also be found in the submandibular and sublingual glands2. The utility of these novel markers merit additional investigation that may facilitate earlier diagnosis and aid in risk stratification. Methods This retrospective chart review included 335 patients from the University of Miami Hospital & Clinics seen within a 5-year span, 01/01/2017 to 12/31/2022. The patients were evaluated across various clinics including Rheumatology, Ophthalmology, Optometry, and Otolaryngology. Patients with sicca syndrome associated with Hepatitis C, AIDS, Sarcoidosis, head and/or neck radiation were excluded. Early Sjogren’s antibody positivity was defined as having a lab value ≥ 25, which is considered strongly positive across various laboratories. This project was approved by the Institutional Review Board, project number 20230415. Results Two hundred and eighty-three charts were included; 52 patients were excluded. Sixty-one percent of charts were positive for 1 or more novel Sjogren’s marker. In patients with positive novel Sjogren’s markers: 38% had a clinical diagnosis of SS, 62% did not. Roughly 50% had rheumatic connective tissue disease (CTD). Of those who did not have CTD, 81% had sicca syndrome. 30% of patients with a positive early marker had a positive SS-A antibody while 70% did not. There was no significant association between novel Sjogren's markers and having a diagnosis of Sjogren’s Syndrome, X2 (1, N = 283) = 1.8, p = .35. In patients with Sjogren’s Syndrome with at least 1 positive marker: 19% had fibromyalgia, 16% had thyroid disease, 10% had neuropathy. In patients with sicca syndrome and extra-glandular manifestations: 28.9% had a diagnosis of thyroid disease, 12.1% had fibromyalgia and 11.6% had neuropathy. Anti CA-6 was the most prevalent antibody across our cohort. Patients with SS with positive novel markers were more likely to have hypocomplementemia, hypergammaglobulinemia but less likely to have thyroid disease vs. patients with SS without positive novel markers however these were not statistically significant. Anti CA-6 was the most prevalent antibody in patients with and without a diagnosis of Sjogren’s Syndrome. In patients with Sjogren’s Syndrome, anti-CA6 was positive in 63.8%, SP1 positive 49.3% then anti-PSP with 34.8%. We also found that the most common ethnicity of patients with positive antibodies in the study was Hispanic or Latino (95 patients, 54.9%) than not Hispanic or Latino (69 patients, 39.9%) and unknown (9 patients, 5.2%) Conclusions In this diverse cohort of patients inclusive of a significant Hispanic population and other minority groups, there was no statistically significant association between the novel Sjogren's markers, and a diagnosis of SS. Findings suggest that these antibodies may not be disease specific. Novel early antibody elevation is consistent with exocrine glandular dysfunction; however, this is not synonymous with SS. In patients with extra-glandular manifestations, early antibody positivity was small. There was a higher percentage of hypocomplementemia & hypergammaglobulinemia in SS patients with positive novel antibodies, but these were not statistically significant. The association between these markers and hypogammaglobulinemia, hypocomplementemia, and elevated thyroid antibodies in SS patients deserves additional investigation. Prospective longitudinal studies are needed to determine whether subgroups of patients with positive novel markers are more likely to develop SS or CTD. References 1. Karakus, S., Baer, A. N., Agrawal, D., Gurakar, M., Massof, R. W., & Akpek, E. K. (2018). Utility of novel autoantibodies in the diagnosis of sjögren’s syndrome among patients with dry eye. Cornea, 37(4), 405–411. doi:10.1097/ico.0000000000001471 2. Shen, L., & Suresh, L. (2017). Autoantibodies, detection methods and panels for diagnosis of Sjögren’s syndrome. Clinical Immunology (Orlando, Fla.), 182, 24–29. doi:10.1016/j.clim.2017.03.017 3. De Langhe, E., Bossuyt, X., Shen, L., Malyavantham, K., Ambrus, J. L., & Suresh, L. (2017). Evaluation of autoantibodies in patients with primary and secondary Sjogren’s syndrome. The Open Rheumatology Journal, 11(1), 10–15. doi:10.2174/1874312901711010010