MMP3 Is a non-invasive biomarker of rejection in skin-bearing vascularized composite allotransplantation

• Verfasst von: Kollár, Branislav [VerfasserIn]
• Verfasst von: Haug, Valentin [VerfasserIn]
• Titel: MMP3 Is a non-invasive biomarker of rejection in skin-bearing vascularized composite allotransplantation
• Titelzusatz: a multicenter validation study
• Verf.angabe: Branislav Kollar, Audrey Uffing, Thiago J. Borges, Andrey V. Shubin, Bruno T. Aoyama, Céline Dagot, Valentin Haug, Martin Kauke, Ali-Farid Safi, Simon G. Talbot, Emmanuel Morelon, Stéphanie Dakpe, Bohdan Pomahac, Leonardo V. Riella
• E-Jahr: 2019
• Jahr: 29 November 2019
• Umfang: 11 S.
• Fussnoten: Gesehen am 14.04.2020
• Titel Quelle: Enthalten in: Frontiers in immunology
• Ort Quelle: Lausanne : Frontiers Media, 2010
• Jahr Quelle: 2019
• Band/Heft Quelle: 10(2019) Artikel-Nummer 2771, 11 Seiten
• ISSN Quelle: 1664-3224
• DOI: doi:10.3389/fimmu.2019.02771
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: acute rejection
• Sach-SW: biomarker
• Sach-SW: face transplantation
• Sach-SW: hand transplantation
• Sach-SW: Vascularized Composite Allotransplantation
• K10plus-PPN: 1694465799

Abstract

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 6 internal and 3 external face transplant recipients, as well as 3 internal and 7 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 and severe rejection) on MMP3 levels. Results: In VCA, MMP3 levels increased significantly (p<0.001) between pre-transplant 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 non-severe rejection 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 (p=0.547). MMP3 levels in healthy controls and autoimmune skin disease patients were comparable with either pre-transplant or no-rejection/non-severe rejection 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.