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Non‐HLA‐Type Endothelial Cell Reactive Alloantibodies in Pre‐Transplant Sera of Kidney Recipients Trigger Apoptosis
Author(s) -
Le BasBernardet Stéphanie,
Hourmant Maryvonne,
Coupel Stéphanie,
Big JeanDenis,
Soulillou JeanPaul,
Charreau Béatrice
Publication year - 2003
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1034/j.1600-6143.2003.00021.x
Subject(s) - medicine , antigen , immunology , human leukocyte antigen , immune system , flow cytometry , tumor necrosis factor alpha , antibody
The vascular endothelium of transplanted organs represents an important target for allograft‐directed immune responses. Although HLA antigens expressed on graft endothelial cells (EC) can become targets of the host immune response, the role of other, non‐HLA‐encoded EC antigens has been proposed but is still unclear. The aim of this study was to investigate the presence of and to characterize anti‐EC antibodies (AECA) in 57 kidney transplant recipients according to their HLA‐immunization status. Flow cytometry in pretransplant sera was used to detect AECA reactive with surface antigens on ABO and HLA‐typed primary cultures of arterial ECs, stimulated or not with tumor necrosis factor‐α (TNFα) or interferon‐γ (IFNγ). FACS analysis revealed the presence of AECA in 47% of HLA‐sensitized (PRA = 10%: mostly IgG) vs. 16.0% in nonsensitized patients (PRA < 10%) (p < 0.02). No significant correlation was found between the presence of AECA and acute rejection occurrence and graft outcome. Non‐HLA reactive AECA are directed against TNFα‐ and IFNγ‐inducible membrane molecule(s), and react with two predominant antigens of ∼35 kDa and ∼50 kDa expressed on ECs but not on B cells. Binding of AECA decreases in vitro EC viability by 50–60% by promoting EC apoptosis, as demonstrated by DNA fragmentation assays .