UCLA researchers in the Department of Dentistry have developed a novel methodology to accurately differentiate patients with Sjögren’s Disease from non-Sjögren’s Disease patients by monitoring saliva IgA1 forms, enabling more accurate tracking of disease progression.
BACKGROUND: The presence and detection of autoantibodies within a host have been a hallmark diagnostic marker for autoimmune illnesses such as Sjögren’s Disease (SD). SD is the second most common autoimmune inflammatory disease and predominantly affects the lacrimal and salivary glands, leading to sicca symptoms (i.e. dry eyes, dry mouth, etc.) in addition to inflammatory arthritis. Because the range of SD symptoms is broad, extending to both gastrointestinal and neurological systems, it is difficult to accurately diagnose due to considerable symptom overlap with other diseases. As such, there are two main manifestations of SD: primary SD (pSS) and secondary SD (sSS). sSS often manifests with other autoimmune disorders such as rheumatoid arthritis (RA). Given the similarity of symptoms seen in SD and other sicca symptom illnesses, there has been a significant effort to develop a set of criteria that can accurately diagnose pSS. The American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have outlined a detailed criteria consisting of a set of quantitative symptoms and clinical tests yielding a score which determines an official pSS diagnosis. One of these clinical tests is a test for IgG and IgA anti–Sjögren's-Syndrome-related antigen A (anti-SSA/Ro) autoantibodies in patient serum. However, the production of these antibodies do not play a part in the actual pathogenesis of pSS and can be found in other systemic autoimmune diseases as well. Further, labial salivary gland biopsies remain as the standard procedure to reliably detect the presence of these antibodies, which is often time-consuming and uncomfortable for patients. Therefore, there is a need for a minimally invasive and accurate diagnostic tool that can distinguish pSS from other Sicca pathologies.
INNOVATION: UCLA researchers led by Dr. David Wong have developed an approach to distinguish primary Sjögren’s Disease patients from sicca patients by monitoring the isomers of IgA1 anti-SSA/Ro autoantibodies within patient saliva. Their assay utilizes plates conjugated with SSA/Ro antigens to the surface for recognition and binding by autoantibody IgA1s. The two subtypes of IgA1, polymeric (pIgA1) and monomeric (mIgA1) forms, can be further discerned by using an additional lectin erythrina cristagalli (ECL) binding agent which only targets monomeric IgA1. This technology combines these two components into the electric field-induced release and measurement (EFIRM) assay method which has been used as a sensitive and effective liquid biopsy platform. The results of this team’s findings have demonstrated that elevated mIgA1is associated with Sicca patients and elevated pIgA1 is specific to pSS patients. Thus, this technology enables an accurate, minimally invasive method to differentiate patients with pSS, allowing for a more accurate diagnosis and treatment.
POTENTIAL APPLICATIONS:
- Accurate diagnostic tool to detect primary Sjögren’s Disease
- Potential usage for Monomeric IgA1s as primary Sjögren’s Disease therapeutic
ADVANTAGES:
- Ability to distinguish IgA1 subclasses which are diseases specific
- Assay can monitor IgA1 for both diagnosis and treatment progression for primary Sjögren’s Disease
- Non-invasive alternative to labial salivary gland biopsies
DEVELOPMENT-TO-DATE: This technology has been shown to successfully demarcate different mIgA1 and pIgA1 levels within patient saliva using incubated patient saliva samples. Methods of saliva sample preparation and storage have also been optimized for rapid assessment using their developed method.
Related Papers (from the inventors only): Chiang S et al. Distinctive profile of monomeric and polymeric anti-SSA/Ro52 immunoglobulin A1 isoforms in saliva of patients with primary Sjögren's Disease and Sicca. RMD Open. 10(2):e003666 (2024)
KEYWORDS: Sjögren’s Disease, sicca, autoimmune, autoantibodies, screening, biopsy, diagnostic methods