Ecto-5′nucleotidase (CD73) May Predict Occurrence and Grade of GVHD in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

BACKGROUND: Graft versus host disease (GVHD) represents a main cause of post-transplant morbidity and mortality. Ectonucleotidases are one of major components of purinergic signaling which is one of the important mediator pathways regulating cellular functions. CD73 is the most significant member of ectonucleotidases. AIM: The aim of the study was to assess role of CD73 in development/severity of GVHD among patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) SUBJECT AND METHODS: This is a prospective study conducted on 30 adult patients eligible for allogeneic HSCT and their 30 donors in a period of 2 years from January 2015 until January 2017. Assessment of CD73 positive cells through flow cytometry on peripheral blood samples in donors during assessment period before receiving G-CSF and in recipients before conditioning at day −7 and once GVHD occurs (within 12 months) or at end of follow-up period was done. RESULTS: CD73 level was significantly higher in recipients pre/post-transplantation (58.24 ± 19.68, 65.78 ± 19.03 respectively) than in donors (29.08 ±14.14) (p = 0.022), there is a significant negative correlation between pre-transplant CD73 level in recipients and occurrence of chronic GVHD (cGVHD), (p = 0.004) and its grade (p = 0.0496). Ectonucleotidase CD73 expression in recipients was a good predictor of cGVHD with sensitivity of 100% and Specificity of 65% at cut off value ≤61.07%. CD73 expression in recipients was independently predicting cGVHD. CONCLUSION: CD 73 may represent a promising, clinically applicable tool of predicting cGVHD and its grade in patients undergoing HSCT.

Purinergic signaling and purine base metabolism at the crossroads between immunity, metabolism, and cancer: A review

“…Inflammatory disorders in the airway are mediated in part by both enhanced levels of adenosine in the bronchoalveolar lavage fluid and by enhanced hyperresponsiveness to adenosine challenge 130 . A prospective clinical study in GVHD found that levels of the CD73 ectonucleotidase in pre‐transplant patients were inversely correlated with occurrence and grade of chronic GVHD, demonstrating an essential and prognostically useful role for CD73 in dampening the immune response in transplants 108 . Other groups who interrogated the role of purines in GVHD found that transplant regimens commonly induced the release of danger‐associated molecular patterns (DAMPs) such as ATP, and that ATP can bind to purinergic receptors on T‐cells to promote a pro‐inflammatory microenvironment that exacerbates GVHD; however, the concentration of ATP and the activation of different purinergic receptors will dictate outcomes 109 .…”

“…Defects in purine signaling and metabolism have been wellcharacterized in several inflammatory diseases including lung disorders such as asthma [98][99][100][101][102] or chronic obstructive pulmonary disease (COPD), [103][104][105][106][107] graft-versus-host-disease (GVHD), [108][109][110][111] ischemiareperfusion injury, [112][113][114][115][116] gastrointestinal (GI) inflammation or inflammatory bowel disorder (IBD) [117][118][119][120][121][122] multiple sclerosis (MS), [123][124][125][126][127] and myasthenia gravis, 128,129 among others. Inflammatory disorders in the airway are mediated in part by both enhanced levels of adenosine in the bronchoalveolar lavage fluid and by enhanced hyperresponsiveness to adenosine challenge.…”