William Dean Wallace1, Ning Li2, Claus B Andersen3, A Valeria Arrossi4, Medhat Askar4, Gerry J Berry5, Matthew M DeNicola6, Desley A Neil7, Elizabeth N Pavlisko8, Elaine F Reed6, Myriam Remmelink9, S Sam Weigt10, Birgit Weynand11, Jennifer Q Zhang6, Marie M Budev12, Carol F Farver4. 1. Department of Pathology, University of California, Los Angeles Medical Center, Los Angeles California. Electronic address: wwallace@mednet.ucla.edu. 2. Department of Biomathematics, University of California, Los Angeles Medical Center, Los Angeles California. 3. Department of Pathology, University of Copenhagen, Copenhagen, Denmark. 4. Department of Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio. 5. Department of Pathology, Stanford University Medical Center, Stanford, California. 6. Department of Pathology, University of California, Los Angeles Medical Center, Los Angeles California. 7. Department of Histopathology, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom. 8. Department of Pathology, Duke University Medical Center, Durham, North Carolina. 9. Department of Pathology, Université Libre de Bruxelles, Brussels, Belgium. 10. Division of Pulmonology, Department of Medicine, University of California, Los Angeles, Los Angeles, California. 11. Department of Pathology, Catholic University of Louvain, Louvain-la-Neuve, Belgium. 12. Pulmonary Medicine, Cleveland Clinic Foundation, Cleveland, Ohio.
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.
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.
Authors: Lufang Liu; Caodi Fang; Whitney Fu; Bo Jiang; Guangxin Li; Lingfeng Qin; Jacob Rosenbluth; Gavin Gong; Catherine B Xie; Peter Yoo; George Tellides; Jordan S Pober; Dan Jane-Wit Journal: Circulation Date: 2019-11-20 Impact factor: 29.690
Authors: S Samuel Weigt; Xiaoyan Wang; Vyacheslav Palchevskiy; Aric L Gregson; Naman Patel; Ariss DerHovanessian; Michael Y Shino; David M Sayah; Shirin Birjandi; Joseph P Lynch; Rajan Saggar; Abbas Ardehali; David J Ross; Scott M Palmer; David Elashoff; John A Belperio Journal: PLoS One Date: 2017-01-19 Impact factor: 3.240
Authors: S Samuel Weigt; Xiaoyan Wang; Vyacheslav Palchevskiy; Xinmin Li; Naman Patel; David J Ross; John Reynolds; Pali D Shah; Lara A Danziger-Isakov; Stuart C Sweet; Lianne G Singer; Marie Budev; Scott Palmer; John A Belperio Journal: J Heart Lung Transplant Date: 2019-05-07 Impact factor: 10.247