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Characteristics of Circulating Donor Human Leukocyte Antigen-specific Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and Kidney Allograft Failure.
Transplantation. 2015 Jun; 99(6):1156-64.T

Abstract

BACKGROUND

Characteristics of pretransplant antibodies directed at donor human leukocyte antigen (HLA) donor-specific antibodies (DSA) associated with adverse outcomes in kidney transplant recipients are being elucidated but uncertainties exist.

METHODS

We prospectively screened pretransplant sera from 543 kidney recipients using single antigen bead assays and identified 154 patients with and 389 without DSA. We investigated the association of DSA features to acute rejection and graft failure.

RESULTS

One-year acute rejection incidence was higher in DSA-positive group (P < 0.001), primarily due to antibody-mediated rejection (AMR, 13% vs. 1.8%, P < 0.001) and not T cell-mediated rejection (ACR, 5% vs.6%, P = 0.65). The sum of mean fluorescence intensity of DSA (DSA MFI-Sum) of 6,000 or higher (OR, 18; 95% CI, 7.0-47; P < 0.001) and the presence of DSA against both HLA class I and II (OR, 39; 95% CI, 14-106; P < 0.0001) predicted 1-year AMR, independent of other covariates. Calculated panel reactive antibody and a positive flow cytometry cross-match result were associated with AMR by bivariate analysis but neither was an independent predictor in a multivariable regression analysis that included DSA-MFI-Sum or HLA DSA class. In multivariable Cox proportional hazards models, the covariate-adjusted hazard ratio for graft failure was 2.03 (95%CI, 1.05-3.92; P = 0.04) for DSA MFI-Sum of 6,000 or higher and 2.23 (95% CI, 1.04-4.80; P = 0.04) for class I and II DSA. Prediction of graft failure was not independent of AMR.

CONCLUSION

Our study suggests that DSA MFI-Sum and HLA class of DSA are characteristics predictive of AMR and graft failure. The elevated risk of graft failure in those with the identified features of DSA is attributable to increased risk of AMR.

Authors+Show Affiliations

1 Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian-Weill Cornell Medical Center, New York, NY. 2 Department of Transplantation, OSF Saint Francis Medical Center, Peroria, IL. 3 Department of Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY. 4 Department of Psychiatry and Behavioral Sciences, Stony Brook University, Stony Brook, NY. 5 Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY. 6 Department of Pathology, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

25629531

Citation

Kannabhiran, Dinesh, et al. "Characteristics of Circulating Donor Human Leukocyte Antigen-specific Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and Kidney Allograft Failure." Transplantation, vol. 99, no. 6, 2015, pp. 1156-64.
Kannabhiran D, Lee J, Schwartz JE, et al. Characteristics of Circulating Donor Human Leukocyte Antigen-specific Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and Kidney Allograft Failure. Transplantation. 2015;99(6):1156-64.
Kannabhiran, D., Lee, J., Schwartz, J. E., Friedlander, R., Aull, M., Muthukumar, T., Campbell, S., Epstein, D., Seshan, S. V., Kapur, S., Sharma, V. K., Suthanthiran, M., & Dadhania, D. (2015). Characteristics of Circulating Donor Human Leukocyte Antigen-specific Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and Kidney Allograft Failure. Transplantation, 99(6), 1156-64. https://doi.org/10.1097/TP.0000000000000511
Kannabhiran D, et al. Characteristics of Circulating Donor Human Leukocyte Antigen-specific Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and Kidney Allograft Failure. Transplantation. 2015;99(6):1156-64. PubMed PMID: 25629531.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characteristics of Circulating Donor Human Leukocyte Antigen-specific Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and Kidney Allograft Failure. AU - Kannabhiran,Dinesh, AU - Lee,John, AU - Schwartz,Joseph E, AU - Friedlander,Rex, AU - Aull,Meredith, AU - Muthukumar,Thangamani, AU - Campbell,Sean, AU - Epstein,David, AU - Seshan,Surya V, AU - Kapur,Sandip, AU - Sharma,Vijay K, AU - Suthanthiran,Manikkam, AU - Dadhania,Darshana, PY - 2015/1/29/entrez PY - 2015/1/30/pubmed PY - 2015/8/19/medline SP - 1156 EP - 64 JF - Transplantation JO - Transplantation VL - 99 IS - 6 N2 - BACKGROUND: Characteristics of pretransplant antibodies directed at donor human leukocyte antigen (HLA) donor-specific antibodies (DSA) associated with adverse outcomes in kidney transplant recipients are being elucidated but uncertainties exist. METHODS: We prospectively screened pretransplant sera from 543 kidney recipients using single antigen bead assays and identified 154 patients with and 389 without DSA. We investigated the association of DSA features to acute rejection and graft failure. RESULTS: One-year acute rejection incidence was higher in DSA-positive group (P < 0.001), primarily due to antibody-mediated rejection (AMR, 13% vs. 1.8%, P < 0.001) and not T cell-mediated rejection (ACR, 5% vs.6%, P = 0.65). The sum of mean fluorescence intensity of DSA (DSA MFI-Sum) of 6,000 or higher (OR, 18; 95% CI, 7.0-47; P < 0.001) and the presence of DSA against both HLA class I and II (OR, 39; 95% CI, 14-106; P < 0.0001) predicted 1-year AMR, independent of other covariates. Calculated panel reactive antibody and a positive flow cytometry cross-match result were associated with AMR by bivariate analysis but neither was an independent predictor in a multivariable regression analysis that included DSA-MFI-Sum or HLA DSA class. In multivariable Cox proportional hazards models, the covariate-adjusted hazard ratio for graft failure was 2.03 (95%CI, 1.05-3.92; P = 0.04) for DSA MFI-Sum of 6,000 or higher and 2.23 (95% CI, 1.04-4.80; P = 0.04) for class I and II DSA. Prediction of graft failure was not independent of AMR. CONCLUSION: Our study suggests that DSA MFI-Sum and HLA class of DSA are characteristics predictive of AMR and graft failure. The elevated risk of graft failure in those with the identified features of DSA is attributable to increased risk of AMR. SN - 1534-6080 UR - https://www.unboundmedicine.com/medline/citation/25629531/Characteristics_of_Circulating_Donor_Human_Leukocyte_Antigen_specific_Immunoglobulin_G_Antibodies_Predictive_of_Acute_Antibody_mediated_Rejection_and_Kidney_Allograft_Failure_ L2 - http://dx.doi.org/10.1097/TP.0000000000000511 DB - PRIME DP - Unbound Medicine ER -