Antibody deposition on vascular endothelial cells contributes to localized inflammation in salivary glands. (12th July 2022)

• Record Type: Journal Article
• Authors: Bagavant, Harini; Trzeciak, Marta; Biswas, Indranil; Papinska, Joanna A.; Cizio, Katarzyna; Deshmukh, Umesh S.
• Is Part Of: Journal of oral pathology & medicine. Volume 51:Number 7(2022)
• Page Start: 674
• Page End: 677
• Publication Date: 2022-07-12
• Subjects: autoantibody -- endothelial cells -- Ro52 -- salivary glands -- Sjögren's disease; Dentistry -- Periodicals; Teeth -- Diseases -- Periodicals; 617
• DOI: 10.1111/jop.13330
• Languages: English
• ISSNs: 0904-2512

Abstract

Abstract: Background: Oral and ocular dryness due to reduced saliva and tear production, exocrine gland inflammation, and autoantibodies to multiple cellular proteins are the cardinal features of Sjögren's Disease. Among the autoantibody specificities, anti‐Ro52 is linked with higher disease severity. We have previously reported that mice immunized with recombinant Ro52 developed IgG deposits in salivary and lacrimal glands and showed reduced saliva and tear production. Furthermore, passive transfer of sera from Ro52‐immunized mice rapidly induced glandular dysfunction without immune cell infiltration in recipient mice. Methods: To identify mechanisms driving antibody‐mediated salivary gland dysfunction, hyperimmune rabbit antiserum to mouse Ro52 was passively transferred into NZM2758 female mice, pretreated with alum adjuvant. Alum‐pretreated mice given hyperimmune rabbit antiserum to maltose‐binding protein served as controls. Antibody deposition and its distribution in the salivary glands were studied by immunofluorescence staining for rabbit IgG, nerve fibers, and endothelial cells. The nCounter inflammation panel was used to determine differentially expressed genes in the salivary gland. Results: Rabbit IgG deposits were detected in salivary glands of anti‐Ro52 immune sera recipients. The rabbit IgG was present on the endothelial cells in small blood vessels, and it did not co‐localize with nerve fibers. Ingenuity pathway analysis of the gene expression dataset predicted the canonical vascular endothelial growth factor (VEGF) pathway as the most activated and Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) as the most inhibited pathway in the salivary glands of anti‐Ro52 sera recipients. Conclusion: Our study suggests that autoantibody deposition on salivary gland endothelial cells might play a critical role in the pathogenesis of Sjögren's Disease.