MMP3 Is a non-invasive biomarker of rejection in skin-bearing vascularized composite allotransplantation: a multicenter validation study
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...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
29 November 2019
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| In: |
Frontiers in immunology
Year: 2019, Volume: 10 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2019.02771 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3389/fimmu.2019.02771 Verlag, lizenzpflichtig, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2019.02771/full 
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Gesehen am 14.04.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2019.02771 |