Increased levels of circulating MMP3 correlate with severe rejection in face transplantation

• Published in: Scientific reports 2018-10, Vol.8 (1), p.14915-12, Article 14915
• Main Authors: Kollar, Branislav, Shubin, Andrey, Borges, Thiago J., Tasigiorgos, Sotirios, Win, Thet Su, Lian, Christine G., Dillon, Simon T., Gu, Xuesong, Wyrobnik, Iris, Murphy, George F., Pomahac, Bohdan, Libermann, Towia A., Riella, Leonardo V.
• Format: Article
• Language: English
• Subjects: 38/61; 631/250/1854/2812; 692/53/2421; 82/1; 82/47; Acute Disease; Adult; Aptamers; Biomarkers; Biomarkers - blood; Biopsy; Cluster Analysis; Enzyme-linked immunosorbent assay; Facial Transplantation - adverse effects; Feasibility studies; Female; Graft rejection; Graft Rejection - blood; Humanities and Social Sciences; Humans; Interleukin 1; Male; Matrix Metalloproteinase 3 - blood; Metalloproteinase; Middle Aged; multidisciplinary; Patients; Proteomics; Reproducibility of Results; Science; Science (multidisciplinary); Transplantation; Transplants & implants; Up-Regulation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-33272-7

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 (r s  = 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.