Saliva Anti-SSA/Ro and Anti-SSB/La for Early Detection of Sjögren’s and SICCA Syndromes

Project Summary/Abstract: Early detection of Sjögren’s Disease (SjD) and its precursor autoimmune-Sicca Syndrome (AI- Sicca), are unmet clinical needs. Serum anti-Ro/SSA autoantibodies and biopsy focus score are two key classification criteria of SjD by the 2016 ACR-EULAR 1. SjD is a complex disease. Clinicians

provide symptomatic treatment to patients as the symptoms of SjD are similar to other physiological and pathological changes in the body including menopause, drug side effects and fibromyalgia amongst others. This leads to a 3-year delay in initial diagnosis from the time the patients first seek medical care. In addition, there is currently no test for the diagnosis of AI-Sicca.

In order to address this unmet clinical need, we have developed a saliva-based electrochemical assay, electric field-induced release and measurement (EFIRM), that can screen, earlier detect and risk assess onset of SjD, alternative to the current ELISA blood-based serology assay. Preliminary data demonstrated: 1) EFIRM can directly detect and quantify salivary anti-SSA/Ro52

autoantibodies in SjD patients; 2) Salivary and serum anti-SSA/Ro52 are correlated in SjD and AI- Sicca patients; 3) Salivary anti-Ro52/SSA IgA1 correlate to salivary gland focus scores. This R21 application will test the hypothesis in a large cohort of SjD and AI-Sicca patients that EFIRM, can: 1) detect anti-SSA/Ro52 and anti-SSB/La in saliva of SjD and AI-Sicca patients, and 2) salivary

IgA1 to SSA/Ro52 is associated with salivary gland tissue destruction as measured by focus scores. Furthermore, monomeric versus polymeric forms for IgA1 to salivary SSA/Ro52 can discriminate SjD from AI-Sicca patients. Should this hypothesis be validated, the EFIRM salivary anti-SSA/Ro52 and anti-SSB/La assays can be explored for early detection of SjD and AI-Sicca in prospective

multi-site clinical study as well as basic science mechanistic pursuits. In addition, saliva monitoring of IgA1 to SSA/Ro52 can be hypothesis tested for monitoring AI-Sicca progression to SjD in a non- invasive sample type (saliva). Three specific aims are proposed for this project. Specific Aim1: Acquire and Characterize Clinical

cohorts of SjD, AI-Sicca and matched control subjects. Specific Aim 2: EFIRM quantitative assessment of anti-SSA/Ro52 and anti-SSB/La in saliva of SjD, AI-Sicca and Controls. EFIRM SSA/Ro52 and SSB/La autoantibody immunoassays will be performed on 210 SjD, 210 AI-Sicca and 315 controls subjects (blinded and randomized). Hypothesis testing of saliva SSA/Ro52 and

SSB/La autoantibodies to discriminate 1) SjD vs AI-Sicca; 2) SjD vs Controls; 3) AI-Sicca vs Controls and 4) (SjD + AI-Sicca) vs Controls. Specific Aim 3: Quantification of monomeric and polymeric anti-SSA/Ro52 IgA1 in saliva of SjD and AI-Sicca patients.