Characterization of ZG16b protein exocrine function and biomarker potential for salivary gland damage in chronic graft vs. host disease

Abstract

Abstract The oral cavity is a frequent target of chronic Graft versus Host Disease (cGVHD) following allogenic hematopoietic stem cell transplant (allo-HSCT). Detection of early cGVHD-induced damage to exocrine tissues, such as salivary glands, is challenging to detect prior to irreversible tissue fibrosis. Recent work in our laboratory used shotgun proteomics to identify putative salivary biomarkers at salivary gland cGVHD onset. Saliva samples from patients affected with oral cGVHD post allo-HSCT had a drop in protein content of zymogen granule 16b (ZG16b), recapitulated in immunohistochemical staining of human minor salivary gland (MSG) biopsy sections. ZG16b loss correlated with CD45+ cells infiltration. This protein is poorly characterized, and immunofluorescence tissue staining suggested ZG16b protein localization to acinar cells. ZG16b cellular expression localized to serous and serous mucous acinar cell populations in single cell RNAseq (scRNA seq) data from healthy human labial MSG. Little is known about the function of this ZG16b in other exocrine tissues such as pancreas. scRNA seq analysis of repository data suggests ZG16b colonization in the pancreatic ductal cells. Similar to MSG, the pancreatic Zg16b gene was expressed in mucus secretion pathways and additional interactions with cell migration and homeostasis markers. Ongoing work is being done to further probe for binding partners for ZG16b (endogenous proteins, components of the oral microbiome and immune cell receptors) to distinguish the protein from its homologs. In parallel, the utility of salivary ZG16b as a cGVHD and general salivary gland damage biomarker is being tested. This work will bring clarity Zg16b’s role in exocrine tissues and alloimmune disease. NIH, NIDCR Intramural program