HLA-C antibodies are associated with irreversible rejection in kidney transplantation: Shared molecular eplets characterization.
We report an interesting case concerning an irreversible antibody-mediated rejection (AMR), associated with anti-HLA-C DSA, which occurred after a second kidney transplantation despite having determined a low number of antibodies directed against HLA-C antigens (MFI<1000) in the previous transplantation (which was then considered to be an indicator of low risk of AMR). A 63-year-old woman was re-transplanted with pre-transplant (PrT) sensitization. On day 7 post-transplantation, oligoanuria occurred and increased MFIs for the detected PrT antibodies and other antibodies (non-detected or detected with very low PrT MFI) were observed. SAB assay also showed antibodies against the second donor HLA-C mismatches and other HLA-C antigens. Nephrologists suspected AMR and the patient was therefore treated with methylprednisolone/plasmapheresis/IVIG/anti-CD20 without improvement, which led to transplantectomy. Histologic analysis confirmed acute AMR. Interestingly, it was possible to define exactly the potential immunizing epitopes whose recognition determines the specific antibody production. So, 1st donor DSAs (detected PrT with low MFI), 2nd donor DSAs (detected PTP), and non-DSA detected PTP have several shared eplets, being the 11AVR eplet the only one present on all alleles. Thus, the recognition of 11AVR eplet in the first transplant modeled the patient's antibody response. Therefore, we propose that donor HLA-C typing should always be performed for recipients with anti-HLA-C antibodies, and specific shared-eplets should be investigated in order to determine previous transplant mismatches.
Department of Immunology, University Hospital Virgen Arrixaca, 30120 Murcia, Spain.
Alexandre
A
Bosch
Department of Nephrology, University Hospital Virgen Arrixaca, 30120 Murcia, Spain.
Santiago
S
Llorente
Department of Immunology, University Hospital Virgen Arrixaca, 30120 Murcia, Spain.
Jorge
J
Eguia
Department of Immunology, University Hospital Virgen Arrixaca, 30120 Murcia, Spain.
Anna
A
Mrowiec
Department of Immunology, University Hospital Virgen Arrixaca, 30120 Murcia, Spain.
Francisco
F
Boix
Department of Immunology, University Hospital Virgen Arrixaca, 30120 Murcia, Spain.
Ruth
R
López-Hernández
Department of Immunology, University Hospital Virgen Arrixaca, 30120 Murcia, Spain.
José A
JA
Campillo
Department of Immunology, University Hospital Virgen Arrixaca, 30120 Murcia, Spain.
Gema
G
Salgado
Department of Immunology, University Hospital Virgen Arrixaca, 30120 Murcia, Spain.
Maria R
MR
Moya-Quiles
Department of Immunology, University Hospital Virgen Arrixaca, 30120 Murcia, Spain.
Alfredo
A
Minguela
Department of Nephrology, University Hospital Virgen Arrixaca, 30120 Murcia, Spain.
Luisa
L
Jimeno
Department of Immunology, University Hospital Virgen Arrixaca, 30120 Murcia, Spain.
María R
MR
Alvarez-López
Department of Immunology, University Hospital Virgen Arrixaca, 30120 Murcia, Spain. Electronic address: manuel.muro@carm.es.
Manuel
M
Muro
D000483:Alleles; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D015236:HLA-C Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D016030:Kidney Transplantation; D008875:Middle Aged; D008958:Models, Molecular; D011487:Protein Conformation
D000939:Epitopes; D015236:HLA-C Antigens