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Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation.
Transpl Immunol 2019; 56:101224TI

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.

Authors+Show Affiliations

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.Allergy, and Critical Care Division, University of California, San Francisco, CA, United States of America.Pulmonary, Allergy, and Critical Care Division, University of Indiana, Indianapolis, Indiana Pulmonary, United States of America.Pulmonary, Allergy, and Critical Care Division, University of Indiana, Indianapolis, Indiana Pulmonary, United States of America.Division of Pulmonary, Critical Care, and Sleep Medicine, University of Florida, Gainesville, FL, United States of America.Pulmonary, Allergy, and Critical Care Division, University of Indiana, Indianapolis, Indiana Pulmonary, United States of America.Pulmonary, Allergy, and Critical Care Division, University of Indiana, Indianapolis, Indiana Pulmonary, United States of America.Pulmonary, Allergy, and Critical Care Division, University of Indiana, Indianapolis, Indiana Pulmonary, United States of America.Pulmonary, Allergy, and Critical Care Division, University of Indiana, Indianapolis, Indiana Pulmonary, United States of America.Lung Transplant Outcomes Group Cohort, Pulmonary, United States of America.Allergy, and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.Pulmonary, Allergy, and Critical Care Division, University of Indiana, Indianapolis, Indiana Pulmonary, United States of America.Allergy, and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31325493

Citation

Zaffiri, Lorenzo, et al. "Collagen type-V Is a Danger Signal Associated With Primary Graft Dysfunction in Lung Transplantation." Transplant Immunology, vol. 56, 2019, p. 101224.
Zaffiri L, Shah RJ, Stearman RS, et al. Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation. Transpl Immunol. 2019;56:101224.
Zaffiri, L., Shah, R. J., Stearman, R. S., Rothhaar, K., Emtiazjoo, A. M., Yoshimoto, M., ... Wilkes, D. S. (2019). Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation. Transplant Immunology, 56, p. 101224. doi:10.1016/j.trim.2019.101224.
Zaffiri L, et al. Collagen type-V Is a Danger Signal Associated With Primary Graft Dysfunction in Lung Transplantation. Transpl Immunol. 2019;56:101224. PubMed PMID: 31325493.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Collagen type-V is a danger signal associated with primary graft dysfunction in lung transplantation. AU - Zaffiri,Lorenzo, AU - Shah,Rupal J, AU - Stearman,Robert S, AU - Rothhaar,Katia, AU - Emtiazjoo,Amir M, AU - Yoshimoto,Momoko, AU - Fisher,Amanda J, AU - Mickler,Elizabeth A, AU - Gartenhaus,Matthew D, AU - Cohort,L T O G, AU - Diamond,Joshua M, AU - Geraci,Mark W, AU - Christie,Jason D, AU - Wilkes,David S, Y1 - 2019/07/17/ PY - 2019/04/12/received PY - 2019/07/09/revised PY - 2019/07/16/accepted PY - 2019/7/22/pubmed PY - 2019/7/22/medline PY - 2019/7/21/entrez KW - Collagen type-V KW - Lung transplant KW - Primary graft dysfunction SP - 101224 EP - 101224 JF - Transplant immunology JO - Transpl. Immunol. VL - 56 N2 - 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. SN - 1878-5492 UR - https://www.unboundmedicine.com/medline/citation/31325493/Collagen_type-V_is_a_danger_signal_associated_with_primary_graft_dysfunction_in_lung_transplantation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0966-3274(19)30045-0 DB - PRIME DP - Unbound Medicine ER -