Increased levels of circulating MMP3 correlate with severe rejection in face transplantation
Abstract
Face transplantation is a viable treatment option for carefully selected patients with devastating injuries to the face. However, acute rejection episodes occur in more than 80% of recipients in the first postoperative year. Unfortunately, neither a correlation between histological grades of rejection and anti-rejection treatment nor systemic surrogate markers of rejection in face transplantation are established in clinical routine. Therefore, we utilized next generation aptamer-based SOMAscan proteomics platform for non-invasive rejection biomarker discovery. Longitudinal serum samples from face transplant recipients with long-term follow-up were included in this study. From the 1,310 proteins analyzed by SOMAscan, a 5-protein signature (MMP3, ACY1, IL1R2, SERPINA4, CPB2) was able to discriminate severe rejection from both no-rejection and nonsevere rejection samples. Technical validation on ELISA platform showed high correlation with the SOMAscan data for the MMP3 protein (rs = 0.99). Additionally, MMP3 levels were significantly increased during severe rejection as compared to no-rejection (p = 0.0009) and nonsevere rejection (p = 0.0173) episodes. Pathway analyses revealed significant activation of the metallopeptidase activity during severe face transplant rejection. This pilot study demonstrates the feasibility of SOMAscan to identify non-invasive candidate biomarkers of rejection in face transplantation. Further validation in a larger independent patient cohort is needed.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 08, 2018
- Source ID
- 10.1038/s41598-018-33272-7
Entities
People
- Andrey Shubin
- Bohdan Pomahač
- Branislav Kollar
- Christine G. Lian
- George F. Murphy
- Iris Wyrobnik
- Leonardo V Riella
- Simon T. Dillon
- Sotirios Tasigiorgos
- Thet Su Win
- Thiago J. Borges
- Towia A Libermann
- Xuesong Gu
Organizations
- National Institutes of Health
- United States Department of Defense