Role of Early Estimation of Regenerating Islet-Derived 3-Alpha (REG3α) in Hematopoietic Stem Cell Transplantation Patients as a Prognostic Marker for Acute Lower Gastrointestinal Graft versus Host Disease

Abstract

Background: REG3α is an antimicrobial protein secreted by Paneth cells with protective effect on Intestinal stem cells (ISCs) and prevents any GI epithelial damage as in GUT GVHD. As its plasma concentration correlate with GUT GVHD activity, it could be used as a biomarker for GUT GVHD. Aim of the work: To evaluate the diagnostic and prognostic role of REG3α in HSCT patients with acute lower gut GVHD. Subjects and methods: Serum level of REG3α was measured using enzyme-linked immunosorbent assay in 45 allogenic haematopoietic stem cell transplantation patients within one week after engraftment in comparison to 20 age and sex-matched healthy control. And reevaluated again in a second sample at patients developed diarrhea due to acute GUT GVHD or any other causes. Then a third sample of REG3α was measured after one week of GUT GVHD treatment. The patients were recruited from Hematopoitic Stem Cells Transplantation Unit (BMT unit) at Ain shams university hospital over the period from 2017 to 2019. Results: Serum level of REG3α after engraftment was significantly elevated > 75 ng/l in patients that developed later acute lower GUT GVHD compared to other patient groups with a sensitivity 100% and specificity 93.3%. REG3α was elevated > 120 ng/l at onset of LGI GVHD symptoms compared to diarrhea due to other causes with a sensitivity 93.33% and specificity 93.33%. After one week of treatment, patients with high levels > 160 ng/l didn’t respond to treatment while patients with levels ≤160 ng/l achieved complete or partial response within 90 days of followup. Conclusion: REG3α is a useful diagnostic and prognostic biomarker for acute lower GUT GVHD and could be used for early prediction of acute LGI GVHD patients after HSCT before clinical presentation.