Lorenzo Zaffiri1, Rupal J Shah2, Robert S Stearman3, Katia Rothhaar3, Amir M Emtiazjoo4, Momoko Yoshimoto3, Amanda J Fisher3, Elizabeth A Mickler3, Matthew D Gartenhaus3, L T O G Cohort5, Joshua M Diamond6, Mark W Geraci3, Jason D Christie6, David S Wilkes7. 1. Pulmonary, Allergy, and Critical Care Division, University of Indiana, Indianapolis, Indiana Pulmonary, United States of America; Division of Pulmonary, Allergy and Critical Care Medicine, Duke University, Durham, NC, United States of America. 2. Allergy, and Critical Care Division, University of California, San Francisco, CA, United States of America. 3. Pulmonary, Allergy, and Critical Care Division, University of Indiana, Indianapolis, Indiana Pulmonary, United States of America. 4. Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, Gainesville, FL, United States of America. 5. Lung Transplant Outcomes Group Cohort, Pulmonary, United States of America. 6. Allergy, and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America. 7. Pulmonary, Allergy, and Critical Care Division, University of Indiana, Indianapolis, Indiana Pulmonary, United States of America; School of Medicine, University of Virginia, Charlottesville, VA, United States of America. Electronic address: dsw4n@virginia.edu.
Abstract
BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of early mortality after lung transplantation. Anti-collagen type-V (col(V)) immunity has been observed in animal models of ischemia-reperfusion injury (IRI) and in PGD. We hypothesized that collagen type-V is an innate danger signal contributing to PGD pathogenesis. METHODS: Anti-col(V) antibody production was detected by flow cytometric assay following cultures of murine CD19+ splenic cells with col.(V). Responding murine B cells were phenotyped using surface markers. RNA-Seq analysis was performed on murine CD19+ cells. Levels of anti-col(V) antibodies were measured in 188 recipients from the Lung Transplant Outcomes Group (LTOG) after transplantation. RESULTS: Col(V) induced rapid production of anti-col(V) antibodies from murine CD19+ B cells. Subtype analysis demonstrated innate B-1 B cells bound col.(V). Col(V) induced a specific transcriptional signature in CD19+ B cells with similarities to, yet distinct from, B cell receptor (BCR) stimulation. Rapid de novo production of anti-col(V) Abs was associated with an increased incidence of clinical PGD after lung transplant. CONCLUSIONS: This study demonstrated that col.(V) is an rapidly recognized by B cells and has specific transcriptional signature. In lung transplants recipients the rapid seroconversion to anti-col(V) Ab is linked to increased risk of grade 3 PGD.
BACKGROUND:Primary graft dysfunction (PGD) is the leading cause of early mortality after lung transplantation. Anti-collagen type-V (col(V)) immunity has been observed in animal models of ischemia-reperfusion injury (IRI) and in PGD. We hypothesized that collagen type-V is an innate danger signal contributing to PGD pathogenesis. METHODS: Anti-col(V) antibody production was detected by flow cytometric assay following cultures of murineCD19+ splenic cells with col.(V). Responding murine B cells were phenotyped using surface markers. RNA-Seq analysis was performed on murineCD19+ cells. Levels of anti-col(V) antibodies were measured in 188 recipients from the Lung Transplant Outcomes Group (LTOG) after transplantation. RESULTS: Col(V) induced rapid production of anti-col(V) antibodies from murineCD19+ B cells. Subtype analysis demonstrated innate B-1 B cells bound col.(V). Col(V) induced a specific transcriptional signature in CD19+ B cells with similarities to, yet distinct from, B cell receptor (BCR) stimulation. Rapid de novo production of anti-col(V) Abs was associated with an increased incidence of clinical PGD after lung transplant. CONCLUSIONS: This study demonstrated that col.(V) is an rapidly recognized by B cells and has specific transcriptional signature. In lung transplants recipients the rapid seroconversion to anti-col(V) Ab is linked to increased risk of grade 3 PGD.
Authors: Alexander McQuiston; Amir Emtiazjoo; Peggi Angel; Tiago Machuca; Jason Christie; Carl Atkinson Journal: Front Immunol Date: 2021-08-11 Impact factor: 7.561
Authors: Michael Keller; Errol Bush; Joshua M Diamond; Pali Shah; Joby Matthew; Anne W Brown; Junfeng Sun; Irina Timofte; Hyesik Kong; Ilker Tunc; Helen Luikart; Aldo Iacono; Steven D Nathan; Kiran K Khush; Jonathan Orens; Moon Jang; Sean Agbor-Enoh Journal: J Heart Lung Transplant Date: 2021-02-20 Impact factor: 13.569
Authors: Mirza Novo; Johan Westin; Lars-Magnus Andersson; Anton Jonsson Berdenius; Rickard Nordén; Jasper M Magnusson Journal: Transplant Direct Date: 2021-07-19