Ricerc@Sapienza

Ocular and oropharyngeal manifestations of chronic graft versus host disease (cGVHD) represent the most frequent mucosal disorders characterized by inflammatory and fibrotic changes associated with xerophthalmia and xerostomia, impairment of quality of life and social functioning. Keratoconjunctivitis sicca (KCS) is the most frequent ocular manifestation of cGVHD causing intense ocular discomfort symptoms and impairment of visual function. A better understanding of pathogenic mechanisms and the availability of biomarkers of activity, severity and/or response to therapies of cGVHD will lead to improvement of GVHD management, quality of life and daily functioning and decrease costs. Neuromediators, including nerve growth factor (NGF), modulate ocular and oropharyngeal inflammation, improve would healing, maintain sensitivity and stimulate tear production. The aims of this prospective, non- interventional study are to: (i) characterize the role of local NGF pathway , neuropeptides and cytokines in cGVHD; (ii) to evaluate the potential use of NGF pathway assessment as biomarker of activity, severity and progression of cGVHD; (iii) to identify subpopulations of patients with cGVHD that could benefit from neuroimmune modulatory drugs. 15 patients with cGVHD and ocular involvement and 15 healthy subjects will be included. Complete ocular, nasal and oropharyngeal examination will be performed at baseline and after 6 and 12 months. Changes of tear, nasal secretion and salivary levels of NGF, pro-NGF, neuropeptides and cytokines and of conjunctival, nasal and oropharyngeal expression of NGF receptors, will be evaluated and related with clinical findings. The results of this study will allow to better understand the role of neuroinflammation in cGVHD with mucosal involvement and to identify potential biomarkers of clinical severity and activity, and novel therapeutic target.