Tags

Type your tag names separated by a space and hit enter

De Novo DQ Donor-Specific Antibodies Are Associated with Chronic Lung Allograft Dysfunction after Lung Transplantation.
Am J Respir Crit Care Med. 2016 09 01; 194(5):596-606.AJ

Abstract

RATIONALE

Despite increasing evidence about the role of donor-specific human leukocyte antigen (HLA) antibodies in transplant outcomes, the incidence and impact of de novo donor-specific antibodies (dnDSA) after lung transplantation remains unclear.

OBJECTIVES

To describe the incidence, characteristics, and impact of dnDSA after lung transplantation.

METHODS

We investigated a single-center cohort of 340 lung transplant recipients undergoing transplant during 2008 to 2011. All patients underwent HLA-antibody testing quarterly pretransplant and at regular intervals over the first 24 months after transplant. The patients received modified immunosuppression depending on their pretransplant sensitization status. Risk factors for dnDSA development, as well as the associations of dnDSA with patient survival and chronic lung allograft dysfunction (CLAD), were determined using multivariable analysis.

MEASUREMENTS AND MAIN RESULTS

The cumulative incidence of dnDSA was 47% at a median of 86 days (range, 44-185 d) after lung transplantation. Seventy-six percent of recipients with dnDSA had DQ-DSA. Male sex and the use of ex vivo lung perfusion were associated with an increased risk of dnDSA, whereas increased HLA-DQB1 matching was protective. DQ-dnDSA preceded or coincided with the diagnosis of CLAD in all cases. Developing dnDSA (vs. no dnDSA) was associated with a twofold increased risk of CLAD (hazard ratio, 2.04; 95% confidence interval, 1.13-3.69). This association appeared to be driven by the development of DQ-dnDSA.

CONCLUSIONS

dnDSA are common after lung transplantation, with the majority being DQ DSA. DQ-dnDSA are associated with an increased risk of CLAD. Strategies to prevent or treat DQ-dnDSA may improve outcomes for lung transplant recipients.

Authors+Show Affiliations

1 Toronto Lung Transplant Program.1 Toronto Lung Transplant Program.2 Division of Nephrology, Department of Medicine, and.2 Division of Nephrology, Department of Medicine, and.1 Toronto Lung Transplant Program.1 Toronto Lung Transplant Program.1 Toronto Lung Transplant Program.1 Toronto Lung Transplant Program.1 Toronto Lung Transplant Program.1 Toronto Lung Transplant Program.2 Division of Nephrology, Department of Medicine, and. 3 HLA Laboratory, Laboratory Medicine Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26967790

Citation

Tikkanen, Jussi M., et al. "De Novo DQ Donor-Specific Antibodies Are Associated With Chronic Lung Allograft Dysfunction After Lung Transplantation." American Journal of Respiratory and Critical Care Medicine, vol. 194, no. 5, 2016, pp. 596-606.
Tikkanen JM, Singer LG, Kim SJ, et al. De Novo DQ Donor-Specific Antibodies Are Associated with Chronic Lung Allograft Dysfunction after Lung Transplantation. Am J Respir Crit Care Med. 2016;194(5):596-606.
Tikkanen, J. M., Singer, L. G., Kim, S. J., Li, Y., Binnie, M., Chaparro, C., Chow, C. W., Martinu, T., Azad, S., Keshavjee, S., & Tinckam, K. (2016). De Novo DQ Donor-Specific Antibodies Are Associated with Chronic Lung Allograft Dysfunction after Lung Transplantation. American Journal of Respiratory and Critical Care Medicine, 194(5), 596-606. https://doi.org/10.1164/rccm.201509-1857OC
Tikkanen JM, et al. De Novo DQ Donor-Specific Antibodies Are Associated With Chronic Lung Allograft Dysfunction After Lung Transplantation. Am J Respir Crit Care Med. 2016 09 1;194(5):596-606. PubMed PMID: 26967790.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - De Novo DQ Donor-Specific Antibodies Are Associated with Chronic Lung Allograft Dysfunction after Lung Transplantation. AU - Tikkanen,Jussi M, AU - Singer,Lianne G, AU - Kim,S Joseph, AU - Li,Yanhong, AU - Binnie,Matthew, AU - Chaparro,Cecilia, AU - Chow,Chung-Wai, AU - Martinu,Tereza, AU - Azad,Sassan, AU - Keshavjee,Shaf, AU - Tinckam,Kathryn, PY - 2016/3/12/entrez PY - 2016/3/12/pubmed PY - 2017/7/20/medline KW - bronchiolitis obliterans syndrome KW - chronic lung allograft dysfunction KW - donor-specific antibodies KW - lung transplantation SP - 596 EP - 606 JF - American journal of respiratory and critical care medicine JO - Am. J. Respir. Crit. Care Med. VL - 194 IS - 5 N2 - RATIONALE: Despite increasing evidence about the role of donor-specific human leukocyte antigen (HLA) antibodies in transplant outcomes, the incidence and impact of de novo donor-specific antibodies (dnDSA) after lung transplantation remains unclear. OBJECTIVES: To describe the incidence, characteristics, and impact of dnDSA after lung transplantation. METHODS: We investigated a single-center cohort of 340 lung transplant recipients undergoing transplant during 2008 to 2011. All patients underwent HLA-antibody testing quarterly pretransplant and at regular intervals over the first 24 months after transplant. The patients received modified immunosuppression depending on their pretransplant sensitization status. Risk factors for dnDSA development, as well as the associations of dnDSA with patient survival and chronic lung allograft dysfunction (CLAD), were determined using multivariable analysis. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of dnDSA was 47% at a median of 86 days (range, 44-185 d) after lung transplantation. Seventy-six percent of recipients with dnDSA had DQ-DSA. Male sex and the use of ex vivo lung perfusion were associated with an increased risk of dnDSA, whereas increased HLA-DQB1 matching was protective. DQ-dnDSA preceded or coincided with the diagnosis of CLAD in all cases. Developing dnDSA (vs. no dnDSA) was associated with a twofold increased risk of CLAD (hazard ratio, 2.04; 95% confidence interval, 1.13-3.69). This association appeared to be driven by the development of DQ-dnDSA. CONCLUSIONS: dnDSA are common after lung transplantation, with the majority being DQ DSA. DQ-dnDSA are associated with an increased risk of CLAD. Strategies to prevent or treat DQ-dnDSA may improve outcomes for lung transplant recipients. SN - 1535-4970 UR - https://www.unboundmedicine.com/medline/citation/26967790/De_Novo_DQ_Donor_Specific_Antibodies_Are_Associated_with_Chronic_Lung_Allograft_Dysfunction_after_Lung_Transplantation_ L2 - http://www.atsjournals.org/doi/full/10.1164/rccm.201509-1857OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -