Noninvasive Biomarkers for Allograft Monitoring After Intestinal Transplantation: Promising Early Results from a Novel Peptide, REG3α
1David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, 2Pediatrics, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, 3Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, 4Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA
Meeting: 2022 American Transplant Congress
Abstract number: 346
Keywords: Intestinal transplantation, Monitoring, Rejection, Screening
Topic: Clinical Science » Small Bowel » 66 - Intestinal Transplantation and Rehabilitation
Session Information
Session Name: Intestinal Transplantation and Rehabilitation
Session Type: Rapid Fire Oral Abstract
Date: Monday, June 6, 2022
Session Time: 5:30pm-7:00pm
Presentation Time: 6:10pm-6:20pm
Location: Hynes Room 206
*Purpose: There is an urgent need for the discovery and application of noninvasive biomarkers to detect allograft rejection after intestinal transplantation (ITx). Calprotectin and citrulline are currently employed but are non-specific. REG3α, a novel intestinal peptide, has been correlated with disease severity in inflammatory bowel disease and intestinal graft vs host disease and has potential as a biomarker for intestinal allograft pathology. However, it has not been extensively studied in ITx.
*Methods: Our center has maintained a detailed prospective database on all ITx recipients since 1991. A protocol of weekly allograft monitoring with stool calprotectin, serum citrulline and endoscopy and biopsy is followed. In 2015, the novel peptide REG3α was added to this protocol. Biopsy-confirmed acute rejection (BCAR) is graded according to international standards. Markers are correlated to BCAR by post-operative week (POW). Analysis compared markers by severity of rejection (grade 0-2 vs 3-4) using standard statistical tests.
*Results: Five adults underwent isolated ITx and one child underwent multivisceral transplantation. Median time to first BCAR was 3 weeks; all experienced at least 1 episode of BCAR. One-year patient and graft survival was 100%. Calprotectin, citrulline and REG3α were significantly associated with grade 3-4 BCAR (p=0.00). The median REG3α level was 5.5 times the upper limit of normal during grade 3-4 BCAR. Calprotectin had the highest positive predictive value (PPV) (76%); REG3α had the highest negative predictive value (NPV) (89%). Together, they demonstrate a high PPV and NPV (100% and 93%, respectively).
| Table 1. Association of noninvasive markers with BCAR | ||||
| BCAR | Mean (± SD) | Median (Range) | P-value | |
| Calprotectin (ug/g)* | none-mild (0/1/2) | 77 (108) | 44 (5-674) | 0.00 |
| moderate-severe (3/4) | 1199 (1289) | 394 (55-3000) | ||
| Citrulline (umol/L)** | none-mild (0/1/2) | 28 (16) | 23 (4-69) | 0.00 |
| moderate-severe (3/4) | 10 (5) | 10 (4-18) | ||
| REG3a (ng/ml)*** | none-mild (0/1/2) | 143 (139) | 143 (20-730) | 0.00 |
| moderate-severe (3/4) | 406 (314) | 406 (99-985) |
normal value: *<120 ug/g, **17-46 umol/L, ***<74.5 ng/mL
*Conclusions: This is the first case series to describe a prospective protocol of allograft monitoring using invasive and noninvasive testing including REG3α. Calprotectin, citrulline and REG3α are individually associated with moderate-severe BCAR and together demonstrate a high PPV and NPV. REG3α demonstrated a superior NPV for the presence of rejection. Further investigations are needed to validate these findings and confirm the role of REG3α.
To cite this abstract in AMA style:
Smullin CP, Venick RS, Marcus EA, Naini BV, Farmer DG. Noninvasive Biomarkers for Allograft Monitoring After Intestinal Transplantation: Promising Early Results from a Novel Peptide, REG3α [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/noninvasive-biomarkers-for-allograft-monitoring-after-intestinal-transplantation-promising-early-results-from-a-novel-peptide-reg3%ce%b1/. Accessed December 3, 2024.« Back to 2022 American Transplant Congress