Clinical Relevance of Posttransplant DSAs in Patients Receiving Desensitization for HLA-incompatible Kidney Transplantation.


Journal

Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144

Informations de publication

Date de publication:
12 2019
Historique:
pubmed: 19 3 2019
medline: 12 6 2020
entrez: 19 3 2019
Statut: ppublish

Résumé

Highly HLA-sensitized (HS) patients have an increased risk for the development of donor-specific antibodies (DSA) and antibody-mediated rejection (AMR) posttransplant. Here, we examined the risk for AMR in HS patients transplanted after desensitization (DES) who were DSA+ versus DSA- at transplant. We also examined the incidence and clinical impact of de novo DSAs (dnDSAs) and compared with dnDSA- patients. From January 2013 to October 2016, 90 HS patients (PRA > 80%, DSA+ = 50 versus DSA- = 40) received kidney transplantation after DES with IVIG + rituximab ± PLEX (plasma exchange) ± tocilizumab. DSAs were monitored at transplant and at 1, 3, 6, 12, 24, 36, and 48 months posttransplant. Patients were divided into 4 groups: DSA+/+ (n = 31), DSA+/- (n=19), DSA-/+ (n=10), and DSA-/- (n = 30). Median follow-up time was 2.9 years. DSA-negative patients who developed dnDSA had the highest incidence of AMR (70%) compared with the DSA+/+ (45%), DSA+/- (11%), and DSA-/- (10%) patients (P < 0.0001). Among patients who developed AMR, Banff 2013 AMR scores did not differ among the 4 groups. Graft survival and estimated glomerular filtration rate determinations at 4 years were similar. Persistence of preexisting DSAs or development of dnDSA after transplant is associated with an increased risk for AMR. Despite this, we did not observe a difference in Banff biopsy scores, graft survival, or patient survival compared with those without DSAs after transplant. Thus, for HS patients undergoing HLA-incompatible kidney transplant, DES therapy and frequent monitoring for dnDSAs appears critical for good long-term survival in at-risk groups.

Sections du résumé

BACKGROUND
Highly HLA-sensitized (HS) patients have an increased risk for the development of donor-specific antibodies (DSA) and antibody-mediated rejection (AMR) posttransplant. Here, we examined the risk for AMR in HS patients transplanted after desensitization (DES) who were DSA+ versus DSA- at transplant. We also examined the incidence and clinical impact of de novo DSAs (dnDSAs) and compared with dnDSA- patients.
METHODS
From January 2013 to October 2016, 90 HS patients (PRA > 80%, DSA+ = 50 versus DSA- = 40) received kidney transplantation after DES with IVIG + rituximab ± PLEX (plasma exchange) ± tocilizumab. DSAs were monitored at transplant and at 1, 3, 6, 12, 24, 36, and 48 months posttransplant.
RESULTS
Patients were divided into 4 groups: DSA+/+ (n = 31), DSA+/- (n=19), DSA-/+ (n=10), and DSA-/- (n = 30). Median follow-up time was 2.9 years. DSA-negative patients who developed dnDSA had the highest incidence of AMR (70%) compared with the DSA+/+ (45%), DSA+/- (11%), and DSA-/- (10%) patients (P < 0.0001). Among patients who developed AMR, Banff 2013 AMR scores did not differ among the 4 groups. Graft survival and estimated glomerular filtration rate determinations at 4 years were similar.
CONCLUSIONS
Persistence of preexisting DSAs or development of dnDSA after transplant is associated with an increased risk for AMR. Despite this, we did not observe a difference in Banff biopsy scores, graft survival, or patient survival compared with those without DSAs after transplant. Thus, for HS patients undergoing HLA-incompatible kidney transplant, DES therapy and frequent monitoring for dnDSAs appears critical for good long-term survival in at-risk groups.

Identifiants

pubmed: 30883456
doi: 10.1097/TP.0000000000002691
doi:

Substances chimiques

HLA Antigens 0
Immunosuppressive Agents 0
Isoantibodies 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2666-2674

Commentaires et corrections

Type : CommentIn

Auteurs

Ashley A Vo (AA)

Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.

Olivier Aubert (O)

Paris Translational Research Center for Organ Transplantation, INSERM U970, Biostatistics Department, Paris, France.

Mark Haas (M)

Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA.

Edmund Huang (E)

Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.

Xiaohai Zhang (X)

Department of HLA and Immunogenetics Lab, Cedars-Sinai Medical Center, Los Angeles, CA.

Jua Choi (J)

Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.

Alice Peng (A)

Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.

Reiad Najjar (R)

Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.

Supreet Sethi (S)

Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.

Nori Ammerman (N)

Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.

Kathlyn Lim (K)

Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.

Stanley C Jordan (SC)

Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.

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