Salivary ZG16B expression loss marks onset of oral Chronic Graft-Versus-Host Disease and exocrine gland dysfunction

Chronic graft-versus-host disease (cGVHD) targets include the oral mucosa and salivary glands after allogeneic hematopoietic stem cell transplant (HSCT). Without incisional biopsy, no diagnostic test exists to confirm oral cGVHD. Consequently, therapy is often withheld until severe manifestations develop. This proteomic study examined saliva and human salivary gland for a biomarker profile at first onset of oral cGVHD prior to initiation of topical steroid therapy. Whole saliva collected at onset of biopsy-proven oral GVHD was assessed using liquid chromatography coupled tandem mass spectrometry with identification of 569 proteins, of which 77 significantly changed in abundance. ZG16B, a secretory lectin protein, was reduced 2-fold in oral cGVHD saliva (p < 0.05), and significantly decreased in salivary gland secretory cells affected by cGVHD. Single-cell RNAseq analysis of healthy MSG localized ZG16B expression to two discreet acinar cell populations. Reduced expression of ZG16B may indicate specific cGVHD activity, general salivary gland dysfunction. Overall design: In this study, we used whole saliva to search for salivary biomarkers of oral cGVHD at disease onset and prior to initiation of topical steroid therapy.