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Specific Donor HLA-DR Types Correlate With Altered Susceptibility to Development of Chronic Lung Allograft Dysfunction.
Transplantation. 2018 07; 102(7):1132-1138.T

Abstract

BACKGROUND

The greatest challenge to long-term graft survival is the development of chronic lung allograft dysfunction. Th17 responses to collagen type V (colV) predispose lung transplant patients to the severe obstructive form of chronic lung allograft dysfunction, known as bronchiolitis obliterans syndrome (BOS). In a previous study cohort (n = 54), pretransplant colV responses were increased in recipients expressing HLA-DR15, consistent with the high binding avidity of colV (α1) peptides for HLA-DR15, whereas BOS incidence, which was known to be strongly associated with posttransplant autoimmunity to colV, was higher in patients who themselves lacked HLA-DR15, but whose lung donor expressed it.

METHODS

To determine if this DR-restricted effect on BOS incidence could be validated in a larger cohort, we performed a retrospective analysis of outcomes for 351 lung transplant recipients transplanted between 1988 and 2008 at the University of Wisconsin. All subjects were followed until graft loss, death, loss to follow-up, or through 2014, with an average follow-up of 7 years. Comparisons were made between recipients who did or did not develop BOS. Grading of BOS followed the recommendations of the international society for heart and lung transplantation.

RESULTS

Donor HLA-DR15 was indeed associated with increased susceptibility to severe BOS in this population. We also discovered that HLA-DR7 expression by the donor or HLA-DR17 expression by the recipient decreased susceptibility.

CONCLUSIONS

We show in this retrospective study that specific donor HLA class II types are important in lung transplantation, because they are associated with either protection from or susceptibility to development of severe BOS.

Authors+Show Affiliations

Transplant Division, Department of Surgery, University of Wisconsin-Madison, Madison, WI.Transplant Division, Department of Surgery, University of Wisconsin-Madison, Madison, WI.Transplant Division, Department of Surgery, University of Wisconsin-Madison, Madison, WI.Transplant Division, Department of Surgery, University of Wisconsin-Madison, Madison, WI.Department of Pulmonology, University of Wisconsin-Madison, Madison, WI.Transplant Division, Department of Surgery, University of Wisconsin-Madison, Madison, WI.

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

29360666

Citation

Haynes, Lynn D., et al. "Specific Donor HLA-DR Types Correlate With Altered Susceptibility to Development of Chronic Lung Allograft Dysfunction." Transplantation, vol. 102, no. 7, 2018, pp. 1132-1138.
Haynes LD, Julliard WA, Mezrich JD, et al. Specific Donor HLA-DR Types Correlate With Altered Susceptibility to Development of Chronic Lung Allograft Dysfunction. Transplantation. 2018;102(7):1132-1138.
Haynes, L. D., Julliard, W. A., Mezrich, J. D., Leverson, G., Meyer, K. C., & Burlingham, W. J. (2018). Specific Donor HLA-DR Types Correlate With Altered Susceptibility to Development of Chronic Lung Allograft Dysfunction. Transplantation, 102(7), 1132-1138. https://doi.org/10.1097/TP.0000000000002107
Haynes LD, et al. Specific Donor HLA-DR Types Correlate With Altered Susceptibility to Development of Chronic Lung Allograft Dysfunction. Transplantation. 2018;102(7):1132-1138. PubMed PMID: 29360666.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Specific Donor HLA-DR Types Correlate With Altered Susceptibility to Development of Chronic Lung Allograft Dysfunction. AU - Haynes,Lynn D, AU - Julliard,Walker A, AU - Mezrich,Joshua D, AU - Leverson,Glen, AU - Meyer,Keith C, AU - Burlingham,William J, PY - 2018/1/24/pubmed PY - 2019/2/20/medline PY - 2018/1/24/entrez SP - 1132 EP - 1138 JF - Transplantation JO - Transplantation VL - 102 IS - 7 N2 - BACKGROUND: The greatest challenge to long-term graft survival is the development of chronic lung allograft dysfunction. Th17 responses to collagen type V (colV) predispose lung transplant patients to the severe obstructive form of chronic lung allograft dysfunction, known as bronchiolitis obliterans syndrome (BOS). In a previous study cohort (n = 54), pretransplant colV responses were increased in recipients expressing HLA-DR15, consistent with the high binding avidity of colV (α1) peptides for HLA-DR15, whereas BOS incidence, which was known to be strongly associated with posttransplant autoimmunity to colV, was higher in patients who themselves lacked HLA-DR15, but whose lung donor expressed it. METHODS: To determine if this DR-restricted effect on BOS incidence could be validated in a larger cohort, we performed a retrospective analysis of outcomes for 351 lung transplant recipients transplanted between 1988 and 2008 at the University of Wisconsin. All subjects were followed until graft loss, death, loss to follow-up, or through 2014, with an average follow-up of 7 years. Comparisons were made between recipients who did or did not develop BOS. Grading of BOS followed the recommendations of the international society for heart and lung transplantation. RESULTS: Donor HLA-DR15 was indeed associated with increased susceptibility to severe BOS in this population. We also discovered that HLA-DR7 expression by the donor or HLA-DR17 expression by the recipient decreased susceptibility. CONCLUSIONS: We show in this retrospective study that specific donor HLA class II types are important in lung transplantation, because they are associated with either protection from or susceptibility to development of severe BOS. SN - 1534-6080 UR - https://www.unboundmedicine.com/medline/citation/29360666/Specific_Donor_HLA_DR_Types_Correlate_With_Altered_Susceptibility_to_Development_of_Chronic_Lung_Allograft_Dysfunction_ L2 - http://dx.doi.org/10.1097/TP.0000000000002107 DB - PRIME DP - Unbound Medicine ER -