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1. Banff study of pathologic changes in lung allograft biopsy specimens with donor-specific antibodies

Author

Wallace, William Dean, Reed, Elaine E.F., Remmelink, Myriam, Sam Weigt, S., Weynand, Birgit, Zhang, Jennifer J.Q., Budev, Marie M.M., Farver, Carol C.F., Li, Ning, Andersen, Claus Boegelund, Arrossi, Andrea Valeria, Askar, Medhat, Berry, Gerry G.J., Denicola, Matthew M.M., Neil, Desley A H D.A., Pavlisko, Elizabeth E.N., Wallace, William Dean, Reed, Elaine E.F., Remmelink, Myriam, Sam Weigt, S., Weynand, Birgit, Zhang, Jennifer J.Q., Budev, Marie M.M., Farver, Carol C.F., Li, Ning, Andersen, Claus Boegelund, Arrossi, Andrea Valeria, Askar, Medhat, Berry, Gerry G.J., Denicola, Matthew M.M., Neil, Desley A H D.A., and Pavlisko, Elizabeth E.N.

Abstract

Background The diagnosis of antibody-mediated rejection (AMR) in the lung transplant is still an area under investigation. We performed a blinded multicenter study to determine if any statistically significant histologic findings in transbronchial biopsy specimens from lung transplant patients correlate with the presence of donor-specific antibodies (DSAs). Methods We asked 9 pathologists with experience in lung transplantation to evaluate 161 lung transplant biopsy specimens for various histologic parameters. The findings were correlated with antibody status positive for DSAs, positive for non-DSAs, and no antibodies (NABs) present. The significance of each histologic variable was reviewed. Results We found no statistically significant association with acute cellular rejection, airway inflammation, or bronchiolitis obliterans and the presence or absence of antibodies. However, biopsy specimens with DSAs had a statistically significant difference vs NABs in the setting of acute lung injury, with or without diffuse alveolar damage (p = 0.0008), in the presence of capillary neutrophilic inflammation (p = 0.0014), and in samples with endotheliitis (p = 0.0155). In samples with complement 4d staining, there was a trend but no statistically significant difference between specimens associated with DSAs and specimens with NABs. Conclusions Capillary inflammation, acute lung injury, and endotheliitis significantly correlated with DSAs. The infrequently observed diffuse staining for complement 4d limits the usefulness of this stain., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2016

2. Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection

Author

Gregson, Aric L., primary, Hoji, Aki, additional, Injean, Patil, additional, Poynter, Steven T., additional, Briones, Claudia, additional, Palchevskiy, Vyacheslav, additional, Sam Weigt, S., additional, Shino, Michael Y., additional, Derhovanessian, Ariss, additional, Sayah, David, additional, Saggar, Rajan, additional, Ross, David, additional, Ardehali, Abbas, additional, Lynch, Joseph P., additional, and Belperio, John A., additional

Published
2015
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3. Correlation between BAL CXCR3 chemokines and lung allograft histopathologies: A multicenter study.

Author

Shino MY, Li N, Todd JL, Neely ML, Kirchner J, Kopetskie H, Sever ML, Frankel CW, Snyder LD, Pavlisko EN, Martinu T, Singer LG, Tsuang W, Budev M, Shah PD, Reynolds JM, Williams N, Robien MA, Palmer SM, Sam Weigt S, and Belperio JA

Subjects
Allografts, Chemokine CXCL9, Lung, Prospective Studies, Chemokine CXCL10, Graft Rejection etiology
Abstract

The histopathologic diagnosis of acute allograft injury is prognostically important in lung transplantation with evidence demonstrating a strong and consistent association between acute rejection (AR), acute lung injury (ALI), and the subsequent development of chronic lung allograft dysfunction (CLAD). The pathogenesis of these allograft injuries, however, remains poorly understood. CXCL9 and CXCL10 are CXC chemokines induced by interferon-γ and act as potent chemoattractants of mononuclear cells. We hypothesized that these chemokines are involved in the mononuclear cell recruitment associated with AR and ALI. We further hypothesized that the increased activity of these chemokines could be quantified as increased levels in the bronchoalveolar lavage fluid. In this prospective multicenter study, we evaluate the incidence of histopathologic allograft injury development during the first-year post-transplant and measure bronchoalveolar CXCL9 and CXCL10 levels at the time of the biopsy. In multivariable models, CXCL9 levels were 1.7-fold and 2.1-fold higher during AR and ALI compared with "normal" biopsies without histopathology. Similarly, CXCL10 levels were 1.6-fold and 2.2-fold higher during these histopathologies, respectively. These findings support the association of CXCL9 and CXCL10 with episodes of AR and ALI and provide potential insight into the pathogenesis of these deleterious events., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Published
2021
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