Profiling posttransplant circulating antibodies in kidney transplantation using donor endothelial cells.
Transplantation
; 93(3): 257-64, 2012 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-22234347
BACKGROUND: Pathogenesis of antibody (Ab) responses to transplant are yet not well defined. This study aimed to detect and to analyze posttransplant circulating allo-Abs reacting toward graft endothelial cells (ECs) using primary EC cultures prospectively isolated from the transplant donor at the time of transplantation. METHODS: This study shows a retrospective analysis performed using a dedicated EC crossmatch (ECXM) assay that we developed for the experimental assessment of donor-specific EC-reactive Abs. Donor-specific ECXM was performed by flow cytometry on posttransplant sera (n=256) from an historical cohort of 22 kidney allograft recipients. RESULTS: In this study, we show that 27.3% (6/22) of recipients have a positive ECXM that strictly correlates (100%, 6/6) with the presence of anti-human leukocyte antigen (HLA) Abs posttransplantation. ECXM identifies both donor-specific Abs (DSA; 50%) and non-DSA (50%) reactive to EC. DSA and non-DSA are mostly IgG1 and exhibit peak titers ranging from 1/8 to 1/1024. ECXM indicates that DSA correspond to anti-HLA class II Abs; this immunization is late (M3-M60) but persistent (still detected at M60). In contrast, non-DSA are non-HLA-type Abs reacting with third-party EC and reflecting an early but transient immunization (ended at M3-M12). Our findings demonstrate selective regulatory pathways initiated by anti-HLA class II and non-DSA in graft EC reflected by CCR4 and interleukin 1ß up-regulation, respectively. CONCLUSIONS: We provide evidence that circulating Abs in HLA-sensitized transplant recipients include both DSA and non-HLA/non-DSA able to bind to graft EC and induce specific gene transcription.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Donantes de Tejidos
/
Prueba de Histocompatibilidad
/
Trasplante de Riñón
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Células Endoteliales
/
Antígenos HLA
/
Isoanticuerpos
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Límite:
Adult
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Transplantation
Año:
2012
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Estados Unidos