Noninvasive evaluation of intragraft immune responses in upper extremity transplantation

Franka Messner; Joanna W. Etra; Jaimie T. Shores; Christopher J. Thoburn; Hubert Hackl; Marcos Iglesias Lozano; Samuel A.J. Fidder; Yinan Guo; Ketevan Kambarashvili; Kemal Alagol; Richa Kalsi; Sarah E. Beck; Carisa Cooney; Georg J. Furtmüller; Johanna Krapf; Byoung Chol Oh; Gerald Brandacher

doi:10.1111/tri.13854

Noninvasive evaluation of intragraft immune responses in upper extremity transplantation

Franka Messner, Joanna W. Etra, Jaimie T. Shores, Christopher J. Thoburn, Hubert Hackl, Marcos Iglesias Lozano, Samuel A.J. Fidder, Yinan Guo, Ketevan Kambarashvili, Kemal Alagol, Richa Kalsi, Sarah E. Beck, Carisa Cooney, Georg J. Furtmüller, Johanna Krapf, Byoung Chol Oh, Gerald Brandacher

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

In vascularized composite allotransplantation (VCA), invasive tissue biopsies remain the gold standard in diagnosing rejection carrying significant morbidity. We aimed to show feasibility of tape-stripping for noninvasive immune monitoring in VCA. Tape-stripping was performed on allografts and native skin of upper extremity transplant recipients. Healthy nontransplanted individuals served as controls. The technique was also used in swine on naïve skin in nontransplanted animals, native skin of treated, transplanted swine, nonrejecting VCAs, and rejecting VCAs. Extracted protein was analyzed for differences in cytokine expression using Luminex technology. Significantly decreased levels of INFγ and IL-1Ra were seen between human allograft samples and native skin. In swine, rejecting grafts had increased IL-1Ra compared to naïve and native skin, decreased levels of GM-CSF compared to native skin, and decreased IL-10 compared to nonrejecting grafts. Unsupervised hierarchical clustering revealed rejecting grafts separated from the nonrejecting (P = 0.021). Variable importance in projection scores identified GM-CSF, IL-1Ra, and IL-2 as the most important profiles for group discrimination. Differences in cytokine expression are detectable in human VCA patient native skin and VCA graft skin using a noninvasive tape-stripping method. Swine studies suggest that differences in cytokines between rejecting and nonrejecting grafts are discernable.

Original language	English (US)
Pages (from-to)	894-905
Number of pages	12
Journal	Transplant International
Volume	34
Issue number	5
DOIs	https://doi.org/10.1111/tri.13854
State	Published - May 2021

Keywords

cytokine profiling
immune monitoring
noninvasive
rejection
skin
vascularized composite allotransplantation

ASJC Scopus subject areas

Transplantation

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10.1111/tri.13854

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Messner, F., Etra, J. W., Shores, J. T., Thoburn, C. J., Hackl, H., Iglesias Lozano, M., Fidder, S. A. J., Guo, Y., Kambarashvili, K., Alagol, K., Kalsi, R., Beck, S. E., Cooney, C., Furtmüller, G. J., Krapf, J., Oh, B. C., & Brandacher, G. (2021). Noninvasive evaluation of intragraft immune responses in upper extremity transplantation. Transplant International, 34(5), 894-905. https://doi.org/10.1111/tri.13854

Messner, F, Etra, JW, Shores, JT , Thoburn, CJ, Hackl, H, Iglesias Lozano, M, Fidder, SAJ, Guo, Y, Kambarashvili, K, Alagol, K, Kalsi, R, Beck, SE, Cooney, C, Furtmüller, GJ, Krapf, J, Oh, BC & Brandacher, G 2021, 'Noninvasive evaluation of intragraft immune responses in upper extremity transplantation', Transplant International, vol. 34, no. 5, pp. 894-905. https://doi.org/10.1111/tri.13854

@article{2e8930a5d94d4b968a95f5016778e020,

title = "Noninvasive evaluation of intragraft immune responses in upper extremity transplantation",

abstract = "In vascularized composite allotransplantation (VCA), invasive tissue biopsies remain the gold standard in diagnosing rejection carrying significant morbidity. We aimed to show feasibility of tape-stripping for noninvasive immune monitoring in VCA. Tape-stripping was performed on allografts and native skin of upper extremity transplant recipients. Healthy nontransplanted individuals served as controls. The technique was also used in swine on na{\"i}ve skin in nontransplanted animals, native skin of treated, transplanted swine, nonrejecting VCAs, and rejecting VCAs. Extracted protein was analyzed for differences in cytokine expression using Luminex technology. Significantly decreased levels of INFγ and IL-1Ra were seen between human allograft samples and native skin. In swine, rejecting grafts had increased IL-1Ra compared to na{\"i}ve and native skin, decreased levels of GM-CSF compared to native skin, and decreased IL-10 compared to nonrejecting grafts. Unsupervised hierarchical clustering revealed rejecting grafts separated from the nonrejecting (P = 0.021). Variable importance in projection scores identified GM-CSF, IL-1Ra, and IL-2 as the most important profiles for group discrimination. Differences in cytokine expression are detectable in human VCA patient native skin and VCA graft skin using a noninvasive tape-stripping method. Swine studies suggest that differences in cytokines between rejecting and nonrejecting grafts are discernable.",

keywords = "cytokine profiling, immune monitoring, noninvasive, rejection, skin, vascularized composite allotransplantation",

author = "Franka Messner and Etra, {Joanna W.} and Shores, {Jaimie T.} and Thoburn, {Christopher J.} and Hubert Hackl and {Iglesias Lozano}, Marcos and Fidder, {Samuel A.J.} and Yinan Guo and Ketevan Kambarashvili and Kemal Alagol and Richa Kalsi and Beck, {Sarah E.} and Carisa Cooney and Furtm{\"u}ller, {Georg J.} and Johanna Krapf and Oh, {Byoung Chol} and Gerald Brandacher",

note = "Funding Information: This work was supported in part by the Army, Navy, NIH, Air Force, VA and Health Affairs to support the AFIRM II effort, under Award No. W81XWH‐13‐2‐0052. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702‐5014 is the awarding and administering acquisition office. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. Funding Information: This work was supported in part by the Army, Navy, NIH, Air Force, VA and Health Affairs to support the AFIRM II effort, under Award No. W81XWH-13-2-0052. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. Publisher Copyright: {\textcopyright} 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd",

year = "2021",

month = may,

doi = "10.1111/tri.13854",

language = "English (US)",

volume = "34",

pages = "894--905",

journal = "Transplant International",

issn = "0934-0874",

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T1 - Noninvasive evaluation of intragraft immune responses in upper extremity transplantation

AU - Messner, Franka

AU - Etra, Joanna W.

AU - Shores, Jaimie T.

AU - Thoburn, Christopher J.

AU - Hackl, Hubert

AU - Iglesias Lozano, Marcos

AU - Fidder, Samuel A.J.

AU - Guo, Yinan

AU - Kambarashvili, Ketevan

AU - Alagol, Kemal

AU - Kalsi, Richa

AU - Beck, Sarah E.

AU - Cooney, Carisa

AU - Furtmüller, Georg J.

AU - Krapf, Johanna

AU - Oh, Byoung Chol

AU - Brandacher, Gerald

N1 - Funding Information: This work was supported in part by the Army, Navy, NIH, Air Force, VA and Health Affairs to support the AFIRM II effort, under Award No. W81XWH‐13‐2‐0052. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702‐5014 is the awarding and administering acquisition office. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. Funding Information: This work was supported in part by the Army, Navy, NIH, Air Force, VA and Health Affairs to support the AFIRM II effort, under Award No. W81XWH-13-2-0052. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. Publisher Copyright: © 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd

PY - 2021/5

Y1 - 2021/5

N2 - In vascularized composite allotransplantation (VCA), invasive tissue biopsies remain the gold standard in diagnosing rejection carrying significant morbidity. We aimed to show feasibility of tape-stripping for noninvasive immune monitoring in VCA. Tape-stripping was performed on allografts and native skin of upper extremity transplant recipients. Healthy nontransplanted individuals served as controls. The technique was also used in swine on naïve skin in nontransplanted animals, native skin of treated, transplanted swine, nonrejecting VCAs, and rejecting VCAs. Extracted protein was analyzed for differences in cytokine expression using Luminex technology. Significantly decreased levels of INFγ and IL-1Ra were seen between human allograft samples and native skin. In swine, rejecting grafts had increased IL-1Ra compared to naïve and native skin, decreased levels of GM-CSF compared to native skin, and decreased IL-10 compared to nonrejecting grafts. Unsupervised hierarchical clustering revealed rejecting grafts separated from the nonrejecting (P = 0.021). Variable importance in projection scores identified GM-CSF, IL-1Ra, and IL-2 as the most important profiles for group discrimination. Differences in cytokine expression are detectable in human VCA patient native skin and VCA graft skin using a noninvasive tape-stripping method. Swine studies suggest that differences in cytokines between rejecting and nonrejecting grafts are discernable.

AB - In vascularized composite allotransplantation (VCA), invasive tissue biopsies remain the gold standard in diagnosing rejection carrying significant morbidity. We aimed to show feasibility of tape-stripping for noninvasive immune monitoring in VCA. Tape-stripping was performed on allografts and native skin of upper extremity transplant recipients. Healthy nontransplanted individuals served as controls. The technique was also used in swine on naïve skin in nontransplanted animals, native skin of treated, transplanted swine, nonrejecting VCAs, and rejecting VCAs. Extracted protein was analyzed for differences in cytokine expression using Luminex technology. Significantly decreased levels of INFγ and IL-1Ra were seen between human allograft samples and native skin. In swine, rejecting grafts had increased IL-1Ra compared to naïve and native skin, decreased levels of GM-CSF compared to native skin, and decreased IL-10 compared to nonrejecting grafts. Unsupervised hierarchical clustering revealed rejecting grafts separated from the nonrejecting (P = 0.021). Variable importance in projection scores identified GM-CSF, IL-1Ra, and IL-2 as the most important profiles for group discrimination. Differences in cytokine expression are detectable in human VCA patient native skin and VCA graft skin using a noninvasive tape-stripping method. Swine studies suggest that differences in cytokines between rejecting and nonrejecting grafts are discernable.

KW - cytokine profiling

KW - immune monitoring

KW - noninvasive

KW - rejection

KW - skin

KW - vascularized composite allotransplantation

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JO - Transplant International

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ER -

Noninvasive evaluation of intragraft immune responses in upper extremity transplantation

Abstract

Keywords

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