Identification of the antibodies involved in B-cell crossmatch positivity in renal transplantation

Bas‐Bernardet, Stéphanie Le; Hourmant, Maryvonne; Valentin, Nathalie; Paitier, Catherine; Giral‐Classe, Magali; Curry, Sylvie; Folléa, Gilles; Soulillou, Jean‐Paul; Bignon, Jean-Denis

doi:10.1097/01.tp.0000047311.77702.59

Cited by 94 publications

(59 citation statements)

References 23 publications

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“…In a previous study, we showed that positive BCXM in a population of 62 patients resulted from autoantibodies for 16% and donor-specific anti-HLA class II Abs for 23%, while 61% of cases remained unexplained (17). To assess whether AECA could explain some B cell reactivity, the presence of AECA was analyzed in regard to BCXM but regardless of immunization.…”

Section: Resultsmentioning

confidence: 99%

“…The control group included 25 non-HLA-immunized (PRA < 10%) patients, most of whom (21/25) had received a first transplant. Methods for the screening of anti-HLA immunization, autoantibodies and lymphocyte cross-matches have been previously reported (17). Briefly, donor and recipient HLA-A, B, DR and DQ typings were performed using a routine complement-dependent microlymphocytotoxicity (CDC) assay completed, when necessary, by polymerase chain reaction with sequence-specific primers (PCR-SSP: MicroSSP class II, One Lambda, Canoga Park, CA, USA) for the determination of HLA-DR or DQ alleles.…”

Section: Patients and Seramentioning

confidence: 99%

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Non-HLA-Type Endothelial Cell Reactive Alloantibodies in Pre-Transplant Sera of Kidney Recipients Trigger Apoptosis

Bas‐Bernardet

Hourmant

Coupel

et al. 2003

American Journal of Transplantation

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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 HLAimmunization 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-a (TNFa) or interferon-g (IFNg). 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 TNFa-and IFNg-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.

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Section: Resultsmentioning

confidence: 99%

Section: Patients and Seramentioning

confidence: 99%

Non-HLA-Type Endothelial Cell Reactive Alloantibodies in Pre-Transplant Sera of Kidney Recipients Trigger Apoptosis

Bas‐Bernardet

Hourmant

Coupel

et al. 2003

American Journal of Transplantation

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“…The main reason for the controversial outcomes in the literature is the lack of studies to confirm DSA. Le Bas-Bernardet et al (20) showed that only 23% of B cell cross-match-positive patients had DSA and demonstrated lower allograft survival, whereas cross-match-positive patients without DSA had similar graft survival to that of B cell cross-match-negative control subjects. Bray et al (21) showed that whereas patients with pretransplantation-positive FC cross-match and 0% FlowPRA had 100% 1-yr graft survival, it was only 40% in patients with both FC cross-match positivity and DSA by FlowPRA.…”

Section: Discussionmentioning

confidence: 99%

Addition of Plasmapheresis Decreases the Incidence of Acute Antibody-Mediated Rejection in Sensitized Patients with Strong Donor-Specific Antibodies

Akalin

Dinavahi

Friedlander

et al. 2008

Clinical Journal of the American Society of Nephrology

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Background and objectives: The objective of this study was to investigate the effects of desensitization protocols using intravenous Ig with or without plasmapheresis in patients with donor-specific anti-HLA antibodies on prevention of antibody-mediated rejection and downregulation of donor-specific antibodies.Design, setting, participants, & measurements: Thirty-five complement-dependent cytotoxicity T cell cross-match-negative but complement-dependent cytotoxicity B cell and/or flow cytometry cross-match-positive kidney transplant recipients were treated with high-dosage intravenous Ig plus Thymoglobulin induction treatment. Donor-specific antibody strength was stratified as strong, medium, or weak by Luminex flow beads. Group 1 patients had weak/moderate and group 2 strong donor-specific antibodies Results: Whereas no group 1 patients had acute rejection, 66% of group 2 had acute rejection (44% antibody-mediated rejection, 22% cellular rejection). The protocol was then changed to the addition of peritransplantation plasmapheresis to patients with strong donor-specific antibodies (group 3). This change resulted in a dramatic decrease in the acute rejection rate to 7%. During a median 18 mo of follow-up, patient survival was 100, 100, and 93% and graft survival was 100, 78, and 86% in groups 1, 2, and 3, respectively. During follow-up, 17 (52%) patients lost donor-specific antibodies completely, and 10 (30%) lost some of donor-specific antibodies and/or decreased the strength of existing donor-specific antibodies.Conclusions: These results indicated that in patients with strong donor-specific antibodies, the addition of plasmapheresis to high-dosage intravenous Ig decreases the incidence of acute rejection. The majority of the patients, whether they received intravenous Ig alone or with plasmapheresis, lost their donor-specific antibodies during follow-up.

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“…CLINICAL RESEARCH www.jasn.org bodies, and evidence would suggest that these antibodies correlate better with both morphologic and functional changes than do class I antibodies. [13][14][15][16][17] Other Possible Mechanisms in the Acceleration of Arteriosclerosis Persistently DSAϪ biopsies had increases in grade of arteriosclerosis, slower and not yet significant at 12 months, but highly significant for late biopsies (P ϭ 0.000006). The reasons for this increase are not clear.…”

Section: Role Of Dsa Positivitymentioning

confidence: 99%

Donor-Specific Antibodies Accelerate Arteriosclerosis after Kidney Transplantation

Hill

Nochy²,

Bruneval³

et al. 2011

Journal of the American Society of Nephrology

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In biopsies of renal allografts, arteriosclerosis is often more severe than expected based on the age of the donor, even without a history of rejection vasculitis. To determine whether preformed donor-specific antibodies (DSAs) may contribute to the severity of arteriosclerosis, we examined protocol biopsies from patients with (n ϭ 40) or without (n ϭ 59) DSA after excluding those with any evidence of vasculitis. Among DSA-positive patients, arteriosclerosis significantly progressed between month 3 and month 12 after transplant (mean Banff cv score 0.65 Ϯ 0.11 to 1.12 Ϯ 0.10, P ϭ 0.014); in contrast, among DSA-negative patients, we did not detect a statistically significant progression during the same timeframe (mean Banff cv score 0.65 Ϯ 0.11 to 0.81 Ϯ 0.10, P ϭ not significant). Available biopsies at later time points supported a rate of progression of arteriosclerosis in DSA-negative patients that was approximately one third that in DSA-positive patients. Accelerated arteriosclerosis was significantly associated with peritubular capillary leukocytic infiltration, glomerulitis, subclinical antibody-mediated rejection, and interstitial inflammation. In conclusion, these data support the hypothesis that donorspecific antibodies dramatically accelerate post-transplant progression of arteriosclerosis.

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Identification of the antibodies involved in B-cell crossmatch positivity in renal transplantation

Cited by 94 publications

References 23 publications

Non-HLA-Type Endothelial Cell Reactive Alloantibodies in Pre-Transplant Sera of Kidney Recipients Trigger Apoptosis

Non-HLA-Type Endothelial Cell Reactive Alloantibodies in Pre-Transplant Sera of Kidney Recipients Trigger Apoptosis

Addition of Plasmapheresis Decreases the Incidence of Acute Antibody-Mediated Rejection in Sensitized Patients with Strong Donor-Specific Antibodies

Donor-Specific Antibodies Accelerate Arteriosclerosis after Kidney Transplantation

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