Salivary ZG16B expression loss follows exocrine gland dysfunction related to oral chronic graft-versus-host disease

Abstract

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 discrete acinar cell populations. Reduced ZG16B expression may indicate specific cGVHD activity and possibly general salivary gland dysfunction.

High-Resolution Transcriptomic Landscape of the Human Submandibular Gland

“…In a similar vein, ductal cells of the human SMG also show molecularly distinct clusters, suggesting the existence hitherto of unappreciated cell types that could be important for SMG homeostasis and regeneration. These observations, overall, dovetail well with the findings from the scRNA-seq data for the human parotid and minor glands (Huang et al 2021;Chen et al 2022;Costa-da-Silva et al 2022). Finally, it is worth noting that our scRNA-seq analysis provides direct support for the evolutionarily conserved ASCL3 + ionocytes, a recently described cell population in the mouse SMG (Mauduit et al 2022).…”

“…7). Taken together, our results highlight the level of cellular heterogeneity of the human SMG, most prominently displayed by the acinar cells (Hauser et al 2020;Costa-da-Silva et al 2022).…”

Grading of minor salivary gland immuno-histopathology post-allogenic hematopoietic cell transplantation

“…We acknowledge that salivary gland damage might be due to the conditioning regimes, unspecific trauma, and a response of overall cGVHD, which is difficult to determine but it highlights the need for large cohort defined clinicopathological studies. Thus, it is crucial to identify early diagnostic criteria for sg-cGVHD and saliva biomarkers could potentially serve this purpose in the future [ 40 , 41 ].…”

GZMK+CD8+ T cells Target a Specific Acinar Cell Type in Sjögren’s Disease

“…Instead of subdividing these populations manually, two overlapping populations were collapsed into a single "PRR4-Transitioning SMACs" population. The most "stem-like" cells identi ed were a subpopulation of cells clustering within the ductal cell cluster subsequently named 'Ductal Progenitors' (KRT5) 32 . Exploring the SMAC cells across this trajectory score, genes of ductal differentiation fall in expression (WFDC2) and genes associated with seromucous acinar function increase in expression (ZG16B, PRR4; Fig.…”