M3 RECEPTOR--DIAGNOSTIC MARKER FOR SJOGREN'S SYNDROME

DESCRIPTION (provided by applicant): Sjogren's syndrome is a human autoimmune disease of the salivary and lacrimal glands that results in a debilitating xerostomia (dry mouth) and xerophthalmia (dry eyes). This syndrome may present as either a primary autoimmune disease or as a secondary autoimmune disease most often concomitant with other connective tissue diseases or diabetes. Although classified as an orphan disease, Sjogren's syndrome is grossly under-diagnosed; thus, it is estimated as many as 2-4 million individuals (90 percent of whom are women) actually have a form of this disease. At present, diagnosis of Sjogren's syndrome involves detection of lymphocytic infiltrates in biopsies of the labial glands; the presence of rheumatoid factor, serum antibodies reactive with cellular components (e.g., SS-A/Ro, SS-B/La, alpha-fodrin and/or nuclear factors), hypergamma-globulinemia, and loss of exocrine gland flow rates. None of these markers, by itself, is disease specific. Recently, we and others have shown that all sera from patients with confirmed Sjogren's syndrome contain antibody to the type-3 muscarinic acetylcholine receptor (M3R) expressed on exocrine tissues. This autoantigen, therefore, appears to be the single marker able to define autoimmune exocrinopathy. Work carried out under our Phase I grant has shown the feasibility of establishing an ELISA-based assay that utilizes a full-length recombinant form of human M3R to detect anti-M3R autoantibody in Sjogren's syndrome patients. Thus, the specific aims of this Phase II grant are to 1) complete the development of the ELISA-based assay, 2) obtain both analytical and clinical performance data for the ELISA-based assay, and 3) determine the precise association between the detection of anti-M3R autoantibody and prediction of disease in Sjogren's syndrome patients. Final development of a simple, non-surgical, Sjogren's syndrome-specific diagnostic test would be a welcome addition to the patient, the treating physician, and the clinical laboratory.