Repository for Antibody Incompatible Transplantation Evidence
343 results
  • Alarabi A
  • Backman U
  • Wikström B
  • Sjöberg O
  • Tufveson G
Int J Artif Organs. 1997 Jan;20(1):51-6.

Immunosensitization against the human lymphocyte antigen (HLA) is a problem in most transplant centers. It prolongs the waiting list time in addition to risk of frequent acute rejections. To avoid these problems, various pretransplantation approaches have been attempted e.g. plasmapheresis (PP). The present retrospective study reports our experience with PP in this respect over a 5 year period. Twenty-three chronic hemodialysis patients with circulating panel reactive antibodies (> or = 50%) and previous kidney graft rejections were treated with 12 PP each. In addition to this, immunosuppression with cyclophosphamide and prednisolone were administered on the first day of PP and after tapering continued until transplantation. HLA-antibodies, as measured by the panel reactive antibodies and the antibody titer, decreased from about 70% to 30% (p < 0.001) and 5 steps of titerdilution, respectively with PP and immunosuppressive drugs; Twenty-two patients were transplanted with cadaveric grafts. Eight grafts were lost due to irreversible rejection, and one due to the patient's death 2 months after transplantation. The cumulative five-year graft survival at the time of follow-up was 59%. Adequate kidney function (serum creatinine mean 150 mumol/l) was observed in all grafts (n = 3) still functioning 60 months posttransplant. We conclude that pretransplantation plasmapheresis together with immunosuppressive drugs (cyclophosphamide and prednisolone) is useful in the removal of HLA antibodies in immunized patients awaiting kidney transplantation. It can be considered a valuable approach to increase the chances of successful transplantations.

  • Higgins RM
  • Bevan DJ
  • Carey BS
  • Lea CK
  • Fallon M
  • Bühler R
  • Vaughan RW
  • O'Donnell PJ
  • Snowden SA
  • Bewick M
  • et al.
Lancet. 1996 Nov 2;348(9036):1208-11 doi: 10.1016/s0140-6736(96)03452-6.
BACKGROUND:

Many patients with circulating antibodies to human leucocyte antigens (anti-HLA) are highly sensitised against renal transplantation and are liable to immediate graft loss through hyperacute rejection. Our aim was to find out whether removal of anti-HLA immediately before renal transplantation prevented hyperacute graft rejection.

METHODS:

13 highly sensitised patients underwent cadaveric renal transplants immediately after immunoadsorption (IA) treatment to remove anti-HLA. Before IA, 12 patients had a positive crossmatch against donor cells either by cytotoxic or flow-cytometric assay; results for one patient were equivocal.

FINDINGS:

Renal biopsy samples were obtained 20 min after removal of the vascular clamps in nine patients. There was no evidence of hyperacute rejection in six of the nine patients; the other three patients showed glomerular thrombosis but no other evidence of hyperacute rejection. Two of these three grafts were functioning at 31 months of follow-up. Six episodes of acute rejection occurred in five patients during the first month after transplantation and overall there were 13 rejection episodes in nine patients. At latest follow-up (median 26 months, range 9-42), 12 of 13 patients were alive and seven of 13 grafts were surviving with a median plasma creatinine concentration of 185 mumol/L (range 106-296) in the functioning grafts. No graft was lost as a result of classic hyperacute rejection.

INTERPRETATION:

Immediate pretransplant IA can prevent hyperacute rejection and provide an opportunity for successful transplantation in highly sensitised patients.

  • Reisaeter AV
  • Leivestad T
  • Albrechtsen D
  • Holdaas H
  • Hartmann A
  • Sødal G
  • Flatmark A
  • Fauchald P
Transplantation. 1995 Aug 15;60(3):242-8 doi: 10.1097/00007890-199508000-00006.

Patients with preformed antibodies against HLA molecules accumulate on renal transplant waiting lists and have inferior graft survival compared with nonsensitized patients. One hundred patients were included in a program of pretransplant removal of antibodies by plasma exchange (n = 90) or immunoadsorption (n = 10) in addition to prednisolone and cyclophosphamide medication. After plasma exchange, the panel reactivity and the antibody titer were reduced in about half of the patients, and after immunoadsorption the panel reactivity fell in 6 of 10 patients. Of the 83 patients who received grafts, 17 received a graft from a living donor (LD) and 66 received a graft from a cadaver donor (CD). Patients with a positive crossmatch against their LD were included in the program and were thus grafted with a recent positive, current negative crossmatched organ. Fifteen CD graft recipients had a pretreatment positive crossmatch toward their donor. No episodes of hyperacute rejection were seen. One- and 4-year graft survival rates in LD transplants with a recent positive and current negative crossmatch were 77% and 64%, respectively. At 1 and 4 years, graft survival rates were 70% and 57% in pretreated first CD graft recipients (n = 27) and 61% and 47% in pretreated regrafted patients (n = 39), respectively. In this program, a high rate of transplantation among the sensitized patients was achieved. Graft survival was inferior to that seen in nonsensitized patients, but was comparable to graft survival in sensitized patients at other centers.

  • Glotz D
  • Haymann JP
  • Niaudet P
  • Lang P
  • Druet P
  • Bariety J
Transplant Proc. 1995 Feb;27(1):1038-9.
  • Cecka JM
  • Terasaki PI
Transplantation. 1994 Feb 27;57(4):515-9.

Should HLA antigens that were mismatched in a renal transplant that failed be avoided in subsequent transplants? There were 890 retransplantations reported to the UCLA International Kidney Transplant Registry between 1985 and 1993 that had been performed in the face of a repeat HLA incompatibility. The 1- and 3-year regraft survival rates were 67% and 55%, respectively, for these retransplants, compared with 73% and 60% for 3220 regrafts with no HLA-A, -B, or -DR antigens mismatched twice (P = 0.030). When the repeat HLA-mismatched antigens were examined by locus, there was no difference in regraft survival comparing patients with no repeat HLA incompatibilities with those mismatched twice for HLA-A or -B antigens only, but there was a significant long-term decrease in survival of patients mismatched twice for HLA-DR antigens. The 377 patients mismatched twice only for HLA-A or -B antigens had 1- and 3-year regraft survival rates of 67% and 59%, respectively, compared with 65% (P = 0.289) and 50% (P = 0.025) for 281 patients with HLA-DR repeat mismatches only. Repeat mismatches for a combination of HLA-A or -B and -DR antigens resulted in 65% and 44% 1- and 3-year regraft survival in 129 patients. The half-lives for retransplants with repeat HLA class I, II, and I and II incompatibilities were 8, 6, and 4 years, respectively (P = 0.005). The data do not support preemptive avoidance of repeat HLA-A or -B incompatibilities. The crossmatch test excludes relevant mismatches. Repeated HLA-DR incompatibilities are not excluded by crossmatch tests and have a deleterious effect on long-term regraft survival. HLA-DR antigens mismatched in a previous failed transplant should be avoided.

  • Kriaa F
  • Hiesse C
  • Farahmand H
  • Bismuth A
  • Charpentier B
Ann Med Interne (Paris). 1994;145(5):324-7.

In an attempt to reduce anti-HLA immunization in 15 patients awaiting for renal grafts and who were immunized against 65% of a panel of lymphocytes (titre 1/8 to 1/128), were given 5 to 7 sessions of immunoadsorption on protein A columns, immunosuppressor drugs (corticosteroids: 1 mg/kg/day + cyclophosphamid: 2 mg/kg/day) and intravenous polyclonal immunoglobulins. The antibody titres decreased in all patients, but this protocol did not sufficiently block resynthesis of antibodies. Among the 12 patients who were transplanted, the graft functioned correctly in 8 after a follow-up of 3 months to 3 years. Three early graft failures occurred in the group of 5 patients whose had had a positive cross-match before treatment. This treatment did not appear to increase the frequency of infectious complications immediately after transplantation.

  • Alarabi AA
  • Nilsson B
  • Nilsson U
  • Wikström B
  • Danielson BG
Artif Organs. 1993 Sep;17(9):782-6 doi: 10.1111/j.1525-1594.1993.tb00631.x.

Antibodies against human lymphocyte antigens (HLA) are frequently seen among patients undergoing repeated renal transplantations. Graft survival can be improved by eliminating these antibodies by plasmapheresis before transplantation. In this study, we have tried a new extracorporeal procedure to remove the anti-HLA antibodies. An immunoadsorption column (IM-TR) with a matrix of polyvinyl alcohol (PVA) gel conjugated with a hydrophobic amino acid tryptophan was utilized. Previous results have shown that repeated IM-TR treatments are at least equally effective as plasmapheresis in reducing levels of specific immunoglobulins in treated patients. In this study, 7 HLA-immunized patients were treated before renal transplantation. Each patient was subjected to a total of 12 treatment sessions divided into 3 sessions per week. After each treatment session, the reduction of the immunoglobulins was less than what has been reported for plasmapheresis. This suggests that mechanisms other than immunoglobulin depletion are involved in the reduction of the total immunoglobulin levels. The IM-TR treatment resulted in a strong complement activation triggered by the alternative pathway. Since the adsorbed plasma was returned to the patient, exceedingly high levels of the activation fragment C3d (C3dg) were found in plasma during and after the treatment. We conclude that the extensive generation of C3dg may be one of the factors that plays a role in the reduction of the antibody levels since the C3dg fragment has been shown to down-regulate the immune response.

  • Glotz D
  • Haymann JP
  • Sansonetti N
  • Francois A
  • Menoyo-Calonge V
  • Bariety J
  • Druet P
Transplantation. 1993 Aug;56(2):335-7 doi: 10.1097/00007890-199308000-00015.

Renal transplantation in patients presenting end-stage renal failure can be hampered by the presence of alloantibodies against HLA antigens. In 4 out of 5 patients with HLA-specific alloantibodies waiting for a renal allograft, treatment with high-dose i.v. Ig resulted in a prolonged suppression (over 3 months) of most of the panel-reactive anti-HLA antibodies (PRA). Intravenous polyclonal human Ig (IVIg) and F(ab')2 fragments from IVIg inhibited the binding of patients' plasma and IgG fractions to peripheral blood lymphocytes from normal donors as well as their cytotoxicity, suggesting that the in vivo effect of IVIg was mediated by the presence, in the IVIg preparation, of anti-idiotypes directed against idiotypes borne on the anti-HLA antibodies. Thus, treatment with IVIg can be a valuable tool toward the transplantation of immunized patients.

  • Ogura K
  • Terasaki PI
  • Johnson C
  • Mendez R
  • Rosenthal JT
  • Ettenger R
  • Martin DC
  • Dainko E
  • Cohen L
  • Mackett T
Transplantation. 1993 Aug;56(2):294-8 doi: 10.1097/00007890-199308000-00007.

This study was conducted to determine the efficacy of the T cell flow cytometry crossmatch (T-FCXM) test in 841 first cadaver donor transplants. Results showed one-year graft survival rates were 82% for T-FCXM-negative patients, compared with 75% for T-FCXM-positive patients (P = 0.01). Early one-month graft failure was 13 percentage points higher in those with a positive T-FCXM than those with a negative T-FCXM. The positive crossmatch patients also had more frequent immunological failures. A positive T-FCXM was found in 39% of the sensitized patients (PRA > 10%) and 8% of those who had not been sensitized. Patients with a positive T-FCXM in either category had a 74% graft survival rate. Thus, most of the T-FCXM-positive results occurred in patients with complement-fixing antibodies. It is suggested that flow cytometry crossmatching (FCXM) be used prospectively, despite the fact that many patients with a positive crossmatch did have successful transplants (TXs). In the current climate of a cadaver kidney scarcity and large recipient waiting pools, utilization of kidneys for patients with the highest probability of success seems a most prudent policy.

  • Alarabi AA
  • Wikström B
  • Backman U
  • Danielson BG
  • Tufvesson G
  • Sjöberg O
Artif Organs. 1993 Aug;17(8):702-7 doi: 10.1111/j.1525-1594.1993.tb00618.x.

Sensitization against human lymphocyte antigen (HLA) occurs frequently in previously transplanted patients that lose a first cadaveric graft. To shorten their time on the waiting list and reduce the incidence of early rejection in such patients, we performed immunoadsorption therapy by a tryptophan column in 10 patients as an attempt to remove circulating antibodies prior to regrafting. Resynthesis of antibodies was suppressed with cyclophosphamide and prednisolone. Following the course of immunoadsorption therapy, the panel reactive antibodies (PRA) decreased by more than 50% from the pretreatment values. In the present study, 8 patients were transplanted with cadaveric renal grafts. At the time of follow-up, graft survival was 63% in these patients (2-36 months post-transplantation, mean 23 months). There was one incidence of acute rejection, one graft was lost within 48 h owing to renal artery thrombosis, and one was lost within 2 weeks as a result of stenosis. The serum creatinine levels were down to near normal during the first 3 weeks in hospital (p < 0.0001) and remained at this level during the period of follow-up. We conclude that immunoadsorption might be a beneficial pretransplantation therapy and an alternative to plasmapheresis in HLA-immunized patients awaiting kidney transplantation.