PMID- 31849957 OWN - NLM STAT- MEDLINE DCOM- 20201103 LR - 20201103 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 10 DP - 2019 TI - MMP3 Is a Non-invasive Biomarker of Rejection in Skin-Bearing Vascularized Composite Allotransplantation: A Multicenter Validation Study. PG - 2771 LID - 10.3389/fimmu.2019.02771 [doi] LID - 2771 AB - Background: There is unmet need for non-invasive immunomonitoring to improve diagnosis and treatment of acute rejection in vascularized composite allotransplantation (VCA). Circulating matrix metalloproteinase 3 (MMP3) was described as a candidate non-invasive biomarker to predict treatment response to acute rejection in clinical VCA. However, larger validation studies are yet to be reported to allow for more definitive conclusions. Methods: We retrospectively measured MMP3 levels using ELISA in a total of 140 longitudinal serum samples from six internal and three external face transplant recipients, as well as three internal and seven external upper extremity transplant recipients. The control groups comprised serum samples from 36 kidney transplant recipients, 14 healthy controls, and 38 patients with autoimmune skin disease. A linear mixed model was used to study the effect of rejection state (pre-transplant, no-rejection, non-severe rejection (NSR), and severe rejection) on MMP3 levels. Results: In VCA, MMP3 levels increased significantly (p < 0.001) between pre- and post-transplant no-rejection states. A further increase occurred during severe rejection (p < 0.001), while there was no difference in MMP3 levels between non-severe and no-rejection episodes. A threshold of 5-fold increase from pre-transplant levels could discriminate severe from NSR with 76% sensitivity and 81% specificity (AUC = 0.79, 95% CI = 0.65-0.92, p < 0.001). In kidney transplantation, the MMP3 levels were significantly (p < 0.001) elevated during antibody-mediated rejection but not during T-cell mediated rejection (TCMR) (p = 0.547). MMP3 levels in healthy controls and autoimmune skin disease patients were comparable with either pre-transplant or no-rejection/NSR episodes of VCA patients. Conclusion: The results of this study suggest that serum MMP3 protein is a promising marker for stratifying patients according to severity of rejection, complementary to biopsy findings. CI - Copyright (c) 2019 Kollar, Uffing, Borges, Shubin, Aoyama, Dagot, Haug, Kauke, Safi, Talbot, Morelon, Dakpe, Pomahac and Riella. FAU - Kollar, Branislav AU - Kollar B AD - Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. FAU - Uffing, Audrey AU - Uffing A AD - Renal Division, Schuster Transplantation Research Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. FAU - Borges, Thiago J AU - Borges TJ AD - Renal Division, Schuster Transplantation Research Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. FAU - Shubin, Andrey V AU - Shubin AV AD - Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, United States. FAU - Aoyama, Bruno T AU - Aoyama BT AD - Renal Division, Schuster Transplantation Research Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. FAU - Dagot, Celine AU - Dagot C AD - Department of Transplantation, Nephrology and Clinical Immunology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. FAU - Haug, Valentin AU - Haug V AD - Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. AD - Department of Hand, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany. FAU - Kauke, Martin AU - Kauke M AD - Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. FAU - Safi, Ali-Farid AU - Safi AF AD - Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. FAU - Talbot, Simon G AU - Talbot SG AD - Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. FAU - Morelon, Emmanuel AU - Morelon E AD - Department of Transplantation, Nephrology and Clinical Immunology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. FAU - Dakpe, Stephanie AU - Dakpe S AD - Department of Maxillo-Facial Surgery, Amiens University Hospital, Amiens, France. FAU - Pomahac, Bohdan AU - Pomahac B AD - Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. FAU - Riella, Leonardo V AU - Riella LV AD - Renal Division, Schuster Transplantation Research Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. LA - eng GR - UL1 TR002541/TR/NCATS NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20191129 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Biomarkers) RN - EC 3.4.24.17 (MMP3 protein, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Adult MH - Autoimmunity MH - *Biomarkers MH - Female MH - Graft Rejection/diagnosis/*etiology/*metabolism MH - Humans MH - Male MH - Matrix Metalloproteinase 3/*metabolism MH - Middle Aged MH - Prognosis MH - ROC Curve MH - Retrospective Studies MH - Severity of Illness Index MH - *Skin Transplantation MH - *Vascularized Composite Allotransplantation PMC - PMC6897344 OTO - NOTNLM OT - acute rejection OT - biomarker OT - face transplantation OT - hand transplantation OT - vascularized composite allotransplantation EDAT- 2019/12/19 06:00 MHDA- 2020/11/04 06:00 PMCR- 2019/01/01 CRDT- 2019/12/19 06:00 PHST- 2019/05/21 00:00 [received] PHST- 2019/11/12 00:00 [accepted] PHST- 2019/12/19 06:00 [entrez] PHST- 2019/12/19 06:00 [pubmed] PHST- 2020/11/04 06:00 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2019.02771 [doi] PST - epublish SO - Front Immunol. 2019 Nov 29;10:2771. doi: 10.3389/fimmu.2019.02771. eCollection 2019.