title: Antibodies against Apoptotic Cells Present in End-stage Lung Disease Patients Do Not Correlate with Clinical Outcome after Lung Transplantation.
abstract: Antibodies against HLA and non-HLA are associated with transplantation outcome. Recently, pretransplant serum IgG antibody levels against apoptotic cells were found to correlate with kidney allograft loss. We investigated the presence of these antibodies in lung transplantation (LTx) patients and evaluated the correlation of pre-LTx serum levels of IgG antibodies against apoptotic cells with LTx outcome. These cells included donor lung endothelial cells (ECs) obtained from lung perfusion fluid collected during LTx procedure. Cells were isolated, expandedin vitro, and analyzed as targets for antiapoptotic cell reactivity. Cultured cells exhibited EC morphology and were CD31+, CD13+, and vWF+. End-stage lung disease patients showed elevated serum IgG levels against apoptotic lung EC (p= 0.0018) compared to healthy controls. Interestingly, the levels of circulating antibodies directed against either apoptotic Jurkat cells or apoptotic lung ECs did not correlate, suggesting a target cell specificity. We observed no correlation between chronic or acute rejection and pre-LTx serum levels of antiapoptotic antibodies. Also, these levels did not differ between matched patients developing chronic rejection or not during follow-up or at the time of diagnosis, as they remained as high as prior to transplantation. Thus, circulating levels of antiapoptotic cell antibodies are elevated in end-stage lung disease patients, but our data do not correlate with outcome after LTx.
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht , Utrecht , Netherlands.
authors.forename: Kevin
authors.initials: K
authors.lastname: Budding
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht , Utrecht , Netherlands.
authors.forename: Eduard A
authors.initials: EA
authors.lastname: van de Graaf
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht , Utrecht , Netherlands.
authors.forename: Tineke
authors.initials: T
authors.lastname: Kardol-Hoefnagel
authors.affiliation: Center of Interstitial Lung Diseases, St. Antonius Hospital , Nieuwegein , Netherlands.
authors.forename: Erik-Jan D
authors.initials: ED
authors.lastname: Oudijk
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht , Utrecht , Netherlands.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Kwakkel-van Erp
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands; Department of Rheumatology, University Medical Center Utrecht, Utrecht, Netherlands; Department of Dermatology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: C Erik
authors.initials: CE
authors.lastname: Hack
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht , Utrecht , Netherlands.
authors.forename: Henny G
authors.initials: HG
authors.lastname: Otten
keywords: antibodies; apoptotic cells; chronic lung allograft dysfunction; lung endothelial cells; lung transplantation