Successful Removal and Prevention of Resynthesis of Anti-Hla Antibody

Taube, David; Welsh, K; Kennedy, Lesley A.; Thick, Michael; Bewick, M.; Cameron, J S; Ogg, C S; Rudge, Chris; Williams, D G

doi:10.1097/00007890-198403000-00007

Cited by 27 publications

(14 citation statements)

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“…Matching at the triplet level increased the median PFD to 0.037% (P=O.O08). The median PFD was 0.058% for a 0-1-triplet mismatch and 0.226% for a 1 Effect of triplet matching on the probability of finding a donor (PFD) for 35 highly sensitized patients. Each patient is identified by a unique number, the %PRA determined by CDC screening and HLA-A,B phenotype.…”

Section: Hlamatchmaker-based Strategy Of Identifying Acceptable Mismamentioning

confidence: 99%

“…Patients are sorted from the lowest to the highest PFD values (on a log10 scale) of finding a donor with a zero-antigen mismatch expressed as percentages. The black bars represent PFD values for the zero-HLA-A,B-antigen mismatches; for patients [1][2][3][4][5][6][7][8][9][10][11] these PFD values were <0.01% or less than 1 in 10,000 donors. The stacked bars represent the cumulative effects of matching at the various triplet levels, namely from 0, to 0-1, and to 0-2 triplets.…”

Section: Hlamatchmaker-based Strategy Of Identifying Acceptable Mismamentioning

confidence: 99%

“…Several strategies have been used to enhance transplantation of highly sensitized patients. One approach is to reduce serum antibody reactivity by exchange plasmapheresis and/or intravenous gammaglobulin treatment [ 1,2,31. Many centers have participated in multi-laboratory strategies, such as the ROP trays in the United States [4], the SOS scheme in the United Kingdom [5], and the HIT program in Europe [6], to crossmatch sera from many sensitized patients so that the chances of finding compatible donors can increase.…”

Section: Introductionmentioning

confidence: 99%

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HLAMatchmaker-based strategy to identify acceptable HLA class I mismatches for highly sensitized kidney transplant candidates

et al. 2004

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HLAMatchmaker determines HLA compatibility at the level of polymorphic amino acid triplets in antibody-accessible sequence positions. Recent studies have shown that among HLA-DR-matched kidney transplants, the HLA-A,B antigen mismatches which are compatible at the triplet level have almost identical graft survival rates as the zero-HLA-A,B antigen mismatches. This finding provides the basis of a new strategy to identify HLA-mismatched organs that have similar success rates as the zero-HLA-antigen mismatches. This report describes how in conjunction with the Acceptable Mismatch program in Eurotransplant, HLAMatchmaker can expand the pool of potential donors for highly sensitized patients, for whom it is very difficult to find a compatible transplant. Sera from 35 highly sensitized kidney transplant candidates with an average PRA of 96% were screened by lymphocytotoxicity with HLAtyped panels that included cells that were selectively mismatched for one or two HLA antigens for each patient. Acceptable and unacceptable HLA-A,B antigen mismatches were determined from the serum reactivity with the cell panel. HLAMatchmaker analysis was applied to identify additional HLA class I antigens that were matched at the triplet level. For each patient, we calculated the probability of finding a donor (PFD) in the different match categories from HLA gene frequencies in the kidney donor population. The median PFD for a zero-antigen mismatch was 0.025%. Matching at the triplet level increased the median PFD to 0.037% (P = 0.008). The median PFD was 0.058% for a 0-1-triplet mismatch and 0.226% for a 0-2-triplet mismatch. Serum screening identified acceptable antigen mismatches for 28 of 35 highly sensitized patients, and the median PFD increased to 0.307% for a zero/ acceptable antigen mismatch. The application of HLAMatchmaker permitted for 33 patients (or 92%) the identification of additional antigens that were acceptable at the triplet level, and the median PFD for a zero/acceptable triplet mismatch went up to 0.425%. Inclusion of one-triplet mismatches increased the median PFD to 1.112%. Validation studies have shown that patient sera reacted with none of the zero-tripletmismatched antigens, 8-13% of the one-triplet mismatches, and 12-19% of the two-triplet mismatches. Although most antigens with one or two mismatched triplets appear acceptable to highly sensitized patients, a serum analysis must ascertain that the patient's antibodies do not recognize such mismatched triplets. HLAMatchmaker offers a useful strategy of identifying more 23 donors with acceptable HLA mismatches and could alleviate the problem of accumulation of highly sensitized patients on the transplant waiting list.

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Section: Hlamatchmaker-based Strategy Of Identifying Acceptable Mismamentioning

confidence: 99%

Section: Hlamatchmaker-based Strategy Of Identifying Acceptable Mismamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HLAMatchmaker-based strategy to identify acceptable HLA class I mismatches for highly sensitized kidney transplant candidates

et al. 2004

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“…These include elimination of unnecessary blood transfusions (27], detection of antibody specificity ie IgG or IgM (28], ensuring good HLA compatibility [29], and removal of preformed allo-antibodies by cyclophosphamide treatment in combination with plasma exchange [30].…”

Section: Sensitizationmentioning

confidence: 99%

Importance of Donor Selection in Renal Transplantation

Chopra

1994

Medical Journal Armed Forces India

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ABSTRACfRenal transplantation has become a treatment of choice for patients with end stage renal disease. A successful transplant is the result of a combination of several factors acting synergistically, such as the degree of HLA compatibility between donor and the recipient, pretransplant blood transfusions, the recipient's state of immunoreactivity and sensitization, immunosuppressive therapy given in post operative period etc. Donor selection appears to be the most critical factor for the long term success of the organ graft. In this brief review, some of the important parameters of donor selection in renal transplantation are highlighted. MJAFI1994; 50: 205·210

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“…Despite success having been limited to those patients where cytotoxicity was directed against one or two of the major HLA antigens [5,6], it seemed important enough to prospectively reexamine the effect of CYA on its own when combined with plasma exchange (PE) on both the spectrum of reac-0 1991 Wiley-Liss, Inc. tivity of the preformed cytotoxic antibodies and their titre.…”

Section: Introductionmentioning

confidence: 99%

Reactivity of pretransplant cytotoxic antibodies to a selected HLA panel is not influenced by cyclosporin a, with or without plasma exchange

Swanepoel

Cassidy

May

et al. 1991

J of Clinical Apheresis

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The influence of 6 weeks of cyclosporin A (CYA), followed by a further 6 weeks of this agent in combination with plasma exchange (PE), was defined on panel reactivity and titre of preformed cytotoxic antibodies in stable patients on haemodialysis awaiting renal transplantation. Nine individuals with antibodies to 30% or more of the donor panel were entered into the study, but three failed to complete the programme. Comprehensive data are available on the remaining six patients, one of whom was studied twice. The pattern of reactivity to the panel was unaltered, but antibody titres were significantly reduced (P less than 0.006). In one patient, a lymphocytoxic crossmatch performed between the patient and an HLA-haploidentical sibling in the last week of the trial was positive, suggesting that neither procedure was successful in removing an antibody directed against the HLA antigens of a family donor. Three cadaver renal transplants were performed during or after the trial, and while two of the grafts were unsuccessful, one survives at 60 months, with good function. From these data it is concluded that neither cyclosporin A nor its combination with plasma exchange have any effect on the panel reactivity of preformed cytotoxic antibodies, whereas the titres were significantly reduced. An important and serious side effect of the apheresis procedure was the loss of fistulae in two patients.

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Successful Removal and Prevention of Resynthesis of Anti-Hla Antibody

Cited by 27 publications

References 0 publications

HLAMatchmaker-based strategy to identify acceptable HLA class I mismatches for highly sensitized kidney transplant candidates

HLAMatchmaker-based strategy to identify acceptable HLA class I mismatches for highly sensitized kidney transplant candidates

Importance of Donor Selection in Renal Transplantation

Reactivity of pretransplant cytotoxic antibodies to a selected HLA panel is not influenced by cyclosporin a, with or without plasma exchange

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