Approximately 40-70% of allogeneic hematopoietic stem cell transplants recipients develop chronic graft-versus-host disease (cGVHD), an autoimmune-like disorder dominated by donor T cells that become reactive against the host. The oral cavity is among the most affected sites in cGVHD. The goal of the present study was to assess whether cytokines and chemokines in patient saliva reflected histopathological features in labial minor salivary gland (MSG).
Method:
Whole saliva samples were collected from oral GVHD patients, and levels of IL-6, IP-10, MCP-1, MDC, MMP9, MMP3, TIMP1, TNFRII, MIG, BD2, RAGE, OPN, and BAFF were measured with a multiplex protein assay. Values were compared between patients with low and high Greenspan scores and patients with low and high Oral Mucositis Rating Scale (OMRS) scores.
Result:
IP-10, MCP-1, and total protein were significantly upregulated (p<0.0001, p<0.004, and p<0.04, respectively) in patients diagnosed with high Greenspan scores versus those with lower Greenspan scores (n=10). MIG was up regulated (p<0.05) in the same cohort. OMRS clinical scores did not correlate with salivary inflammatory mediators (n=32).
Conclusion:
The relationship between inflammatory mediators is better correlated with the histopathology of the MSG biopsy than with clinical scoring of mucosal disease. Higher levels of IP-10, MCP-1, and MIG in saliva highlight the relationship between cellular infiltration into the salivary gland and the concentration and type of proteins present in saliva of cGVHD patients. Upregulation of IP-10 and MIG support the theory that the oral component of cGVHD is an interferon-mediated disease, which has important implications for development of oral cGVHD therapies. Non-invasive saliva sampling could play a significant role in the clinical diagnosis and understanding of oral cGVHD.