Detection of donor-specific anti-HLA antibodies with flow cytometry in eluates and sera from renal transplant recipients with chronic allograft nephropathy1

Martin, Laurent; Guignier, F.; Mousson, Christiane; Rageot, David; Justrabo, E; Rifle, G

doi:10.1097/01.tp.0000078895.24606.45

Cited by 124 publications

(91 citation statements)

References 24 publications

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“…The potential mechanisms supporting this observation warrant further study but would be consistent with increases in measurable alloimmune activity. [22][23][24][25] These data are difficult to interpret conclusively, because the reason for nephrectomy is not known, and we cannot surmise that avoiding nephrectomy would abrogate this risk. These observations must be weighed against the potential survival benefits that have been reported with other studies of allograft nephrectomy.…”

Section: Discussionmentioning

confidence: 88%

“…Nephrectomy can result in an increase in PRA [22][23][24][25] as well as negatively affect subsequent graft survival. 26 Therefore, we specifically examined the effect of RMM in patients with and without nephrectomy of the first allograft occurring before the second transplant and found that class 2 RMM carried increased hazard for DCGL and ACGL, specifically in patients who were nephrectomized.…”

Section: Discussionmentioning

confidence: 99%

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Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation

Tinckam

Rose

Hariharan

et al. 2016

JASN

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Kidney retransplantation is a risk factor for decreased allograft survival. Repeated mismatched HLA antigens between first and second transplant may be a stimulus for immune memory responses and increased risk of alloimmune damage to the second allograft. Historical data identified a role of repeated HLA mismatches in allograft loss. However, evolution of HLA testing methods and a modern transplant era necessitate re-examination of this role to more accurately risk-stratify recipients. We conducted a contemporary registry analysis of data from 13,789 patients who received a second kidney transplant from 1995 to 2011, of which 3868 had one or more repeated mismatches. Multivariable Cox proportional hazards modeling revealed no effect of repeated mismatches on all-cause or death-censored graft loss. Analysis of predefined subgroups, however, showed that any class 2 repeated mismatch increased the hazard of death-censored graft loss, particularly in patients with detectable panel-reactive antibody before second transplant (hazard ratio [HR], 1.15; 95% confidence interval [95% CI], 1.02 to 1.29). Furthermore, in those who had nephrectomy of the first allograft, class 2 repeated mismatches specifically associated with all-cause (HR, 1.30; 95% CI, 1.07 to 1.58) and death-censored graft loss (HR, 1.41; 95% CI, 1.12 to 1.78). These updated data redefine the effect of repeated mismatches in retransplantation and challenge the paradigm that repeated mismatches in isolation confer increased immunologic risk. We also defined clear recipient categories for which repeated mismatches may be of greater concern in a contemporary cohort. Additional studies are needed to determine appropriate interventions for these recipients. 27: 283327: -284127: , 201627: . doi: 10.1681 Kidney retransplantation is generally viewed to increase risk for immunologic damage and graft loss. The increased risk is attributed to the formation of T and B memory cells to mismatched HLA antigens in the original donors. Re-exposure to a repeated HLA antigen mismatched (RMM) in a subsequent donor potentially invokes alloimmune memory responses, resulting in earlier allograft damage and loss. J Am Soc NephrolThe nature and magnitude of this potential risk have changed with reanalysis over time. Whereas a number of studies have described worse allograft survival when repeated antigens are mismatched at the HLA-DR locus, 1-3 with RMM at class 1 (HLA-A or -B) not influencing outcomes, others have shown a beneficial effect of RMM on graft survival 4,5 or a neutral effect. 6,7 A more recent analysis showed an effect of class 1 RMM on graft survival, with no differences seen with class 2 RMM. 8

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation

Tinckam

Rose

Hariharan

et al. 2016

JASN

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“…Overall, the sensitivity of the DbA peptide is encouraging, taking into account: (i) the long time of storage of the FMAIT samples and the destructive effect that this may have had on HPA-1a antibody potency; (ii) that some cases had weakly positive results by MAIPA at the time of referral; and (iii) that the sensitivity may be enhanced by applying the DbA peptides on a fourth-generation assay platform, like the Luminex bead assay, and going through a program of optimization for routine diagnostic use in a clinical setting [34].…”

Section: Dsdl-pro33mentioning

confidence: 99%

Immunologic and structural analysis of eight novel domain-deletion β₃integrin peptides designed for detection of HPA-1 antibodies

Stafford¹,

Ghevaert²,

Campbell³

et al. 2008

J Thromb Haemost

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WH. Immunologic and structural analysis of eight novel domain-deletion b 3 integrin peptides designed for detection of HPA-1 antibodies. J Thromb Haemost 2008; 6: 366-75.See also Stafford P, Garner SF, Huiskes E, Kaplan C, Kekomaki R, Santoso S, Tsuno NH, Watkins NA, Ouwehand WH. Three novel b3 domaindeletion peptides for the sensitive and specific detection of HPA-4 and six low frequency b3-HPA antibodies. This issue, pp 376-83.Summary. Background: The single-nucleotide polymorphism (SNP) rs5918 in the ITGB3 gene defines the human platelet antigen-1 (HPA-1) system encoding a Leu (HPA-1a) or Pro (HPA-1b) at position 33. HPA-1 antibodies are clinically the most relevant in the Caucasoid population, but detection currently requires a IIb b 3 integrin from the platelets of HPAgenotyped donors. Objectives: We set out to define the b 3 integrin domains required for HPA-1a antibody binding and produce recombinant soluble b 3 peptides for HPA-1 antibody detection. Methods: We designed two sets (1a and 1b) of four soluble b 3 domain-deletion peptides (DSDL, DbA, PSIHybrid, PSI), informed by crystallography studies and computer modeling. The footprints of three human HPA-1a-specific phage antibodies were defined by analyzing binding patterns to the b 3 peptides and canine platelets, and models of antibodyantigen interfaces were derived. Specificity and sensitivity for HPA-1a detection were assessed using sera from 140 cases of fetomaternal alloimmune thrombocytopenia (FMAI-T). Results: Fusion of recombinant proteins to calmodulin resulted in high-level expression in Drosophila S2 cells of all eight b 3 peptides. Testing of FMAIT samples indicated that DbA-Leu33 is the superior peptide for HPA-1a antibody detection, with 96% sensitivity and 95% specificity. The existence of type I and II categories of HPA-1a antibodies was confirmed by the study of HPA-1a phage antibody footprints and the reactivity pattern of clinical samples with the four b 3 -Leu33 peptides, but there was no correlation between antibody category and clinical severity of FMAIT. Conclusions: Soluble recombinant b 3 peptides can be used for detection of clinical HPA-1a antibodies.

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“…Antibodies can be eluted from Ͼ70% of rejected kidneys, whereas the sera of patients before rejection may be positive in only approximately 45% of patients (25). This suggests that the antibodies could go undetected in the serum, probably because the kidney is absorbing the antibodies (26).…”

Section: Dsamentioning

confidence: 99%

Antibody Mediated Rejection

Terasaki

Mizutani

2006

Clinical Journal of the American Society of Nephrology

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Detection of donor-specific anti-HLA antibodies with flow cytometry in eluates and sera from renal transplant recipients with chronic allograft nephropathy1

Cited by 124 publications

References 24 publications

Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation

Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation

Immunologic and structural analysis of eight novel domain-deletion β₃integrin peptides designed for detection of HPA-1 antibodies

Antibody Mediated Rejection

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Detection of donor-specific anti-HLA antibodies with flow cytometry in eluates and sera from renal transplant recipients with chronic allograft nephropathy1

Cited by 124 publications

References 24 publications

Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation

Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation

Immunologic and structural analysis of eight novel domain-deletion β3integrin peptides designed for detection of HPA-1 antibodies

Antibody Mediated Rejection

Contact Info

Product

Resources

About

Immunologic and structural analysis of eight novel domain-deletion β₃integrin peptides designed for detection of HPA-1 antibodies