Human leukocyte antigens antibodies after lung transplantation: Primary results of the HALT study

Ramsey R. Hachem; Malek Kamoun; Marie M. Budev; Medhat Askar; Vivek N. Ahya; James C. Lee; Deborah J. Levine; Marilyn S. Pollack; Gundeep S. Dhillon; David Weill; Kenneth B. Schechtman; Lorriana E. Leard; Jeffrey A. Golden; Lee Ann Baxter-Lowe; Thalachallour Mohanakumar; Dolly B. Tyan; Roger D. Yusen

doi:10.1111/ajt.14893

Human leukocyte antigens antibodies after lung transplantation: Primary results of the HALT study

Ramsey R. Hachem, Malek Kamoun, Marie M. Budev, Medhat Askar, Vivek N. Ahya, James C. Lee, Deborah J. Levine, Marilyn S. Pollack, Gundeep S. Dhillon, David Weill, Kenneth B. Schechtman, Lorriana E. Leard, Jeffrey A. Golden, Lee Ann Baxter-Lowe, Thalachallour Mohanakumar, Dolly B. Tyan, Roger D. Yusen

Medicine

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Donor-specific antibodies (DSA) to mismatched human leukocyte antigens (HLA) are associated with worse outcomes after lung transplantation. To determine the incidence and characteristics of DSA early after lung transplantation, we conducted a prospective multicenter observational study that used standardized treatment and testing protocols. Among 119 transplant recipients, 43 (36%) developed DSA: 6 (14%) developed DSA only to class I HLA, 23 (53%) developed DSA only to class II HLA, and 14 (33%) developed DSA to both class I and class II HLA. The median DSA mean fluorescence intensity (MFI) was 3197. We identified a significant association between the Lung Allocation Score and the development of DSA (HR = 1.02, 95% CI: 1.001-1.03, P =.047) and a significant association between DSA with an MFI ≥ 3000 and acute cellular rejection (ACR) grade ≥ A2 (HR = 2.11, 95% CI: 1.04-4.27, P =.039). However, we did not detect an association between DSA and survival. We conclude that DSA occur frequently early after lung transplantation, and most target class II HLA. DSA with an MFI ≥ 3000 have a significant association with ACR. Extended follow-up is necessary to determine the impact of DSA on other important outcomes.

Original language	English (US)
Pages (from-to)	2285-2294
Number of pages	10
Journal	American Journal of Transplantation
Volume	18
Issue number	9
DOIs	https://doi.org/10.1111/ajt.14893
State	Published - Sep 2018

Keywords

clinical research/practice
histocompatibility
lung transplantation/pulmonology
major histocompatibility complex (MHC)
monitoring: immune
rejection: T cell mediated (TCMR)
rejection: antibody-mediated (ABMR)

ASJC Scopus subject areas

Immunology and Allergy
Transplantation
Pharmacology (medical)

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Hachem, R. R., Kamoun, M., Budev, M. M., Askar, M., Ahya, V. N., Lee, J. C., Levine, D. J., Pollack, M. S., Dhillon, G. S., Weill, D., Schechtman, K. B., Leard, L. E., Golden, J. A., Baxter-Lowe, L. A., Mohanakumar, T., Tyan, D. B., & Yusen, R. D. (2018). Human leukocyte antigens antibodies after lung transplantation: Primary results of the HALT study. American Journal of Transplantation, 18(9), 2285-2294. https://doi.org/10.1111/ajt.14893

Human leukocyte antigens antibodies after lung transplantation : Primary results of the HALT study. / Hachem, Ramsey R.; Kamoun, Malek; Budev, Marie M.; Askar, Medhat; Ahya, Vivek N.; Lee, James C.; Levine, Deborah J.; Pollack, Marilyn S.; Dhillon, Gundeep S.; Weill, David; Schechtman, Kenneth B.; Leard, Lorriana E.; Golden, Jeffrey A.; Baxter-Lowe, Lee Ann; Mohanakumar, Thalachallour; Tyan, Dolly B.; Yusen, Roger D.

In: American Journal of Transplantation, Vol. 18, No. 9, 09.2018, p. 2285-2294.

Research output: Contribution to journal › Article › peer-review

Hachem, RR, Kamoun, M, Budev, MM, Askar, M, Ahya, VN, Lee, JC, Levine, DJ, Pollack, MS, Dhillon, GS, Weill, D, Schechtman, KB, Leard, LE, Golden, JA, Baxter-Lowe, LA, Mohanakumar, T, Tyan, DB & Yusen, RD 2018, 'Human leukocyte antigens antibodies after lung transplantation: Primary results of the HALT study', American Journal of Transplantation, vol. 18, no. 9, pp. 2285-2294. https://doi.org/10.1111/ajt.14893

Hachem, Ramsey R. ; Kamoun, Malek ; Budev, Marie M. ; Askar, Medhat ; Ahya, Vivek N. ; Lee, James C. ; Levine, Deborah J. ; Pollack, Marilyn S. ; Dhillon, Gundeep S. ; Weill, David ; Schechtman, Kenneth B. ; Leard, Lorriana E. ; Golden, Jeffrey A. ; Baxter-Lowe, Lee Ann ; Mohanakumar, Thalachallour ; Tyan, Dolly B. ; Yusen, Roger D. / Human leukocyte antigens antibodies after lung transplantation : Primary results of the HALT study. In: American Journal of Transplantation. 2018 ; Vol. 18, No. 9. pp. 2285-2294.

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title = "Human leukocyte antigens antibodies after lung transplantation: Primary results of the HALT study",

abstract = "Donor-specific antibodies (DSA) to mismatched human leukocyte antigens (HLA) are associated with worse outcomes after lung transplantation. To determine the incidence and characteristics of DSA early after lung transplantation, we conducted a prospective multicenter observational study that used standardized treatment and testing protocols. Among 119 transplant recipients, 43 (36%) developed DSA: 6 (14%) developed DSA only to class I HLA, 23 (53%) developed DSA only to class II HLA, and 14 (33%) developed DSA to both class I and class II HLA. The median DSA mean fluorescence intensity (MFI) was 3197. We identified a significant association between the Lung Allocation Score and the development of DSA (HR = 1.02, 95% CI: 1.001-1.03, P =.047) and a significant association between DSA with an MFI ≥ 3000 and acute cellular rejection (ACR) grade ≥ A2 (HR = 2.11, 95% CI: 1.04-4.27, P =.039). However, we did not detect an association between DSA and survival. We conclude that DSA occur frequently early after lung transplantation, and most target class II HLA. DSA with an MFI ≥ 3000 have a significant association with ACR. Extended follow-up is necessary to determine the impact of DSA on other important outcomes.",

keywords = "clinical research/practice, histocompatibility, lung transplantation/pulmonology, major histocompatibility complex (MHC), monitoring: immune, rejection: T cell mediated (TCMR), rejection: antibody-mediated (ABMR)",

author = "Hachem, {Ramsey R.} and Malek Kamoun and Budev, {Marie M.} and Medhat Askar and Ahya, {Vivek N.} and Lee, {James C.} and Levine, {Deborah J.} and Pollack, {Marilyn S.} and Dhillon, {Gundeep S.} and David Weill and Schechtman, {Kenneth B.} and Leard, {Lorriana E.} and Golden, {Jeffrey A.} and Baxter-Lowe, {Lee Ann} and Thalachallour Mohanakumar and Tyan, {Dolly B.} and Yusen, {Roger D.}",

note = "Funding Information: We conducted a prospective observational cohort study of lung transplant recipients at 6 centers in the United States to determine the cumulative incidence of posttransplant DSA, describe their characteristics, and assess their impact on clinical outcomes. The National Institutes of Health funded the study as a 2-year R34 grant (HL 10542). Each site aimed to prescreen/screen all lung transplant candidates placed on the United Network for Organ Sharing (UNOS) waiting list at the institution. Study personnel screened patients for eligibility (Table E1 in the online data supplement) at the time of listing for transplantation or within the first 10 days after transplantation. Enrollment was initiated on December 1, 2011 and completed on June 30, 2012; follow-up was completed on October 28, 2012. Local institutional review boards at each center approved the study protocol, and all participants provided written informed consent. Funding Information: This study was funded by the National Institutes of Health, National",

year = "2018",

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language = "English (US)",

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T2 - Primary results of the HALT study

AU - Hachem, Ramsey R.

AU - Kamoun, Malek

AU - Budev, Marie M.

AU - Askar, Medhat

AU - Ahya, Vivek N.

AU - Lee, James C.

AU - Levine, Deborah J.

AU - Pollack, Marilyn S.

AU - Dhillon, Gundeep S.

AU - Weill, David

AU - Schechtman, Kenneth B.

AU - Leard, Lorriana E.

AU - Golden, Jeffrey A.

AU - Baxter-Lowe, Lee Ann

AU - Mohanakumar, Thalachallour

AU - Tyan, Dolly B.

AU - Yusen, Roger D.

N1 - Funding Information: We conducted a prospective observational cohort study of lung transplant recipients at 6 centers in the United States to determine the cumulative incidence of posttransplant DSA, describe their characteristics, and assess their impact on clinical outcomes. The National Institutes of Health funded the study as a 2-year R34 grant (HL 10542). Each site aimed to prescreen/screen all lung transplant candidates placed on the United Network for Organ Sharing (UNOS) waiting list at the institution. Study personnel screened patients for eligibility (Table E1 in the online data supplement) at the time of listing for transplantation or within the first 10 days after transplantation. Enrollment was initiated on December 1, 2011 and completed on June 30, 2012; follow-up was completed on October 28, 2012. Local institutional review boards at each center approved the study protocol, and all participants provided written informed consent. Funding Information: This study was funded by the National Institutes of Health, National

PY - 2018/9

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N2 - Donor-specific antibodies (DSA) to mismatched human leukocyte antigens (HLA) are associated with worse outcomes after lung transplantation. To determine the incidence and characteristics of DSA early after lung transplantation, we conducted a prospective multicenter observational study that used standardized treatment and testing protocols. Among 119 transplant recipients, 43 (36%) developed DSA: 6 (14%) developed DSA only to class I HLA, 23 (53%) developed DSA only to class II HLA, and 14 (33%) developed DSA to both class I and class II HLA. The median DSA mean fluorescence intensity (MFI) was 3197. We identified a significant association between the Lung Allocation Score and the development of DSA (HR = 1.02, 95% CI: 1.001-1.03, P =.047) and a significant association between DSA with an MFI ≥ 3000 and acute cellular rejection (ACR) grade ≥ A2 (HR = 2.11, 95% CI: 1.04-4.27, P =.039). However, we did not detect an association between DSA and survival. We conclude that DSA occur frequently early after lung transplantation, and most target class II HLA. DSA with an MFI ≥ 3000 have a significant association with ACR. Extended follow-up is necessary to determine the impact of DSA on other important outcomes.

AB - Donor-specific antibodies (DSA) to mismatched human leukocyte antigens (HLA) are associated with worse outcomes after lung transplantation. To determine the incidence and characteristics of DSA early after lung transplantation, we conducted a prospective multicenter observational study that used standardized treatment and testing protocols. Among 119 transplant recipients, 43 (36%) developed DSA: 6 (14%) developed DSA only to class I HLA, 23 (53%) developed DSA only to class II HLA, and 14 (33%) developed DSA to both class I and class II HLA. The median DSA mean fluorescence intensity (MFI) was 3197. We identified a significant association between the Lung Allocation Score and the development of DSA (HR = 1.02, 95% CI: 1.001-1.03, P =.047) and a significant association between DSA with an MFI ≥ 3000 and acute cellular rejection (ACR) grade ≥ A2 (HR = 2.11, 95% CI: 1.04-4.27, P =.039). However, we did not detect an association between DSA and survival. We conclude that DSA occur frequently early after lung transplantation, and most target class II HLA. DSA with an MFI ≥ 3000 have a significant association with ACR. Extended follow-up is necessary to determine the impact of DSA on other important outcomes.

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KW - lung transplantation/pulmonology

KW - major histocompatibility complex (MHC)

KW - monitoring: immune

KW - rejection: T cell mediated (TCMR)

KW - rejection: antibody-mediated (ABMR)

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