Sjögren’s disease (SjD) is a systemic autoimmune disorder that targets the exocrine glands, resulting in the hallmark symptoms of dry eye and dry mouth. The pathogenesis is multifactorial as hormonal factors, genetic predispositions, and environmental insults combine to cause inappropriate lymphocyte activation and subsequent lymphocytic infiltration of exocrine glands [1]. Extraglandular involvement via immune-complex deposition, lymphoproliferation, and chronic inflammatory responses is common. Serious complications may arise in long-standing or severe disease including peripheral neuropathy, B-cell lymphoma, and interstitial nephritis [1], [2], [3], [4].

The estimated prevalence of SjD ranges from 1 in every 1,000 to 10,000 individuals, and the condition disproportionately affects females with a female to male ratio of 9:1 [3], [5], [6]. In the US, SjD has an estimated prevalence of 0.4 to 3.4 million people [7]. Approximately 10% of patients that present to ophthalmologists with clinically significant dry eye disease (DED) have underlying SjD [2], [8], [9], [10]. Notably, keratoconjunctivitis sicca in SjD may also precede formal diagnosis for up to 10 years, presenting ophthalmologists with a unique opportunity to be among the first providers to identify these patients and initiate the timely appropriate evaluations and multidisciplinary management [11]. However, DED is also a common condition that affects up to 33% of individuals older than 50 years of age, making it difficult to ascertain which patients should pursue a systemic workup for SjD [12]. Diagnosing SjD is also inherently difficult due to its clinical heterogeneity, leading to years of delay in diagnosis [3], [13], [14]. Furthermore, the diagnosis of SjD can be complex, requiring a multidisciplinary approach.

Although autoantibody testing is a quick and simple first step for screening and diagnosis, traditional SjD autoantibodies (anti-nuclear antibody (ANA), rheumatoid factor (RF), anti-Ro/SS-A, and anti-La/SS-B), are not present in all patients with SjD. For instance, the prevalence of SS-A antibodies in SjD ranges from 60-74% depending on method of detection and the patients studied.[15], [16]. Additionally, SS-A antibodies may disappear with time in some instances [17], [18].

In the past decade, serum murine autoantibodies specific to the salivary gland proteins in the nonobese diabetic (NOD) and interleukin-14 (IL-14) transgenic mouse models of SjD have been identified and appear earlier in the disease course than traditional SjD antibodies [18]. These three autoantigens are salivary gland protein-1 (SP-1), carbonic anhydrase VI (CA VI), and parotid secretory protein (PSP). Prior studies have provided some evidence that these novel autoantibodies are more prevalent in patients with SjD compared to those without SjD, suggesting that these novel markers could potentially be employed as part of a screening or diagnostic test [8], [19]. If validated, these novel antibody markers could aid in the screening of patients with DED for suspected SjD while also possibly serving as a substitute for minor salivary gland biopsy for diagnosis.

However, prior studies looking at the prevalence of the novel murine autoantibodies in humans have been limited by differing approaches towards defining SjD status, which included the use of different methods of assessment and definitions of an abnormal test result, as well as different classification and/or diagnostic criteria [18], [20], [21], [22], [23], [24]. In addition, many of these studies did not complete SjD workups on all patients and utilized small sample sizes, potentially amplifying the effects of these various approaches and generating diverse cohorts of SjD and reference groups.

In order to learn more about the novel SjD autoantibodies, this project assessed the prevalence of these autoantibodies in a well-characterized, multi-center cohort of dry eye patients. Participants were also stratified by labial salivary gland biopsy status to evaluate for any associations between biopsy status and these murine tissue-specific autoantibodies.