Transplantation of patients possessing antibodies against allo-HLA antigens can be delayed for years. We have shown that administration of intravenous immunoglobulins (IVIg) can induce a profound and sustained decrease in the titers of anti-HLA antibodies. We report here the first series of patients desensitized, then transplanted using IVIg therapy. Fifteen patients have been included and treated with IVIg, given as 3 monthly courses of 2g/kg body weight. Thirteen of those 15 patients (87%) were effectively desensitized and underwent immediate transplantation. Eleven were transplanted with a cadaveric donor, and two with a living donor against which the pretreatment cross-match was positive. One graft was lost from thrombosis and one from rejection. All other patients had uneventful courses, without any episodes of rejection, with a follow-up of more than 1 year. Thus, IVIg therapy allows safe and prompt kidney transplantation of immunized patients.

• Ovid Technologies, Inc.

The importance of certain positive crossmatches (CM+) in kidney transplantation remains controversial. Fifty consecutive kidney transplants were performed across a CM+ between Jan. 1990-April 1994. In 19 cases there was an isolated B-cell CM+ (Group I), in 24 an historic T-cell IgM CM+ (Group II) and in 7 an historic T-cell IgG CM+ (Group III). Comparing groups I:II:III: early acute rejection affected 32%, 42%, 57% of grafts; mean serum creatinine at 3 months was 166, 150, 229 umol/l (p < 0.05); 1 yr graft survival was 95 per cent, 96 per cent, 71 per cent (p = 0.09). In group III both graft losses were in the setting of an additional current B-cell CM+.

Transplantation performed in either the presence of an isolated B-cell CM+ or in the presence of an historic T-cell IgM CM+ was associated with acceptable outcomes at 1 yr. An historic T-cell IgG CM+ was confirmed as a contraindication to transplantation in most circumstances, especially when coupled with a current B-cell CM+.

• Ovid Technologies, Inc.

Differential cross-matches have been proposed to allow immunised patients to be grafted, whereas the dogma of a global positive cross-match discarded them from renal transplantation. We report our one-center experience considering current T positive cross-match as the only contra-indication to grafting, as well as patients whose sera comprise specific anti-donor antibodies. A comprehensive characterization of the antibodies was achieved by identification of auto-antibodies and specification of IgM and IgG isotype, class I and class II specificities, as well as HLA specificities. The differential cross-match comprised an auto and an allo-cross-match, against T and B lymphocytes. Historical and current sera were analysed either untreated or after DTT-treatment, at +4 degrees C and +22 degrees C. We performed 79 renal transplantations across positive cross-matches, which were 20 historical T positive cross-matches, 26 historical B positive cross-matches and 33 current B positive cross-matches. Results and graft survival were strictly identical as those obtained in the transplantations achieved with negative cross-matches throughout the same period, especially in sensitized patients. Current positive B cell cross-matches due to IgG were associated with an increased risk for early graft failure. We conclude that differential cross-match is a safe strategy permitting immunised patients to be grafted.

Donor-recipient HLA matching was retrospectively evaluated in 111 cadaveric renal transplants using Takemoto's ten-residue model in which HLA class I antigens are clustered by crossreactive group (CREGs) on the basis of amino acid sequence homology and the sharing of a particular public epitope. The grade and type of HLA residue mismatching were correlated to posttransplant, class I donor-specific antibody production (monitored by flow cytometry crossmatch), rejection occurrence and clinical outcome during the 1st year posttransplant. In 52 patients with 0 mismatchings (MMs) we observed a low incidence of rejection (11.1%) and antibody production (11.1%) for 0 CREG MM grade, while 1 MM was enough to increase immune response against graft (rejection 35%; antibodies 30%). Moreover, a significant correlation was observed between Q144, E163, Q62 and L82/R82 epitopes and the incidence of acute rejection and antibody production ("immunogenic" residues) in patients grouped for a single residue mismatch.

• Springer

In the preparation of patients for renal transplantation tests of human leucocyte antigen (HLA) sensitisation are performed to detect "unacceptable" HLA antigens that, if present on donor cells, would be expected to result in a positive crossmatch. Individuals bearing such specificities may then be excluded from consideration as donors. Unexpected positive crossmatch results are sometimes obtained when a serum specificity has not been detected on screening. Failure to identify a donor relevant HLA antibody in a recipient at the time of crossmatch may result in hyperacute rejection of the graft. This report describes laboratory investigations performed after a positive crossmatch result in a live donor situation. The pattern of crossmatch results indicated that reactivity resulted from HLA class I antibody. Previously performed serum screening using a standard complement dependent cytotoxicity technique had failed to identify donor relevant antibody specificities in the recipient. Retrospective flow cytometric screening of the same serum samples identified an HLA-A24 specificity of donor relevance. The lower sensitivity of methods used for routine serum screening compared with those used for crossmatching accounts for the findings in this case. The laboratory has amended its serum screening protocol to include flow cytometric analysis.

• Europe PubMed Central
• PubMed Central
• HighWire

• Ovid Technologies, Inc.

A positive crossmatch with a "current" recipient serum (drawn shortly before the proposed transplant) is a contraindication to renal transplantation because of the risk of hyperacute rejection. Conflicting data have been reported concerning the significance of a positive crossmatch with "remote" sera (obtained months or years earlier) when the current crossmatch is negative.

Recipients of a first or second cadaver transplant between June 1988 and April 1994 were studied. All transplants were performed with a negative "current" crossmatch. Retrospective crossmatches using "remote" sera were performed for all sensitized recipients.

Recipients with a positive remote crossmatch (RXM) demonstrated a higher incidence of delayed graft function and of acute rejection and graft loss occurring in the first year posttransplant than did sensitized recipients with a negative RXM or unsensitized recipients. In multivariate analysis, only recipients with both a positive RXM and delayed graft function were at significantly higher risk for graft loss. Grafts surviving the first year demonstrated similar half-lives whether the RXM was positive or negative.

The positive RXM, possibly in conjunction with other factors leading to very early graft damage, is a significant predictor of unfavorable transplant outcome in first and second renal transplants. This effect is seen early in the transplant course, and there seems to be no impact on outcome after the first year. Newer immunosuppressive modalities may help to reduce the early negative impact.

• Wolters Kluwer
• Ovid Technologies, Inc.

• Elsevier Science

Alloimmunization can present a virtually insurmountable barrier to kidney transplantation. Past protocols to desensitize patients using plasmapheresis and cyclophosphamide have not been broadly applied because of the fear of complications, including high rates of immunologic failure.

Fifteen patients with a positive donor-recipient cross-match were desensitized with plasmapheresis to permit live donor (LD) transplantation under newer maintenance immunosuppressants. Pretransplant the patients received plasmapheresis three times weekly for a planned maximum of six treatments, plus intravenous hyperimmune globulin, tacrolimus, mycophenolate mofetil, and prednisone. Patients who were successfully desensitized and received transplants were given 10 days of OKT3 postoperatively.

Eleven of the 15 patients became anti-human globulin cross-match-negative after one to five plasmapheresis treatments and underwent LD transplantation. Relatively low initial titers of donor-specific antibody were predictive of successful attainment of a negative cross-match. Few side effects and rejection episodes were observed. All transplant patients remain dialysis-free after 3-26 months of follow-up.

A positive cross-match is not necessarily a contraindication to LD transplantation, especially for patients with low donor-specific alloantibody titers.

• Wolters Kluwer
• Ovid Technologies, Inc.

Re-transplanted kidney allograft recipients with high levels of panel reactive antibodies (PRA) are at increased risk of early immunologic graft loss. In these patients, prophylactic peri-operative antibody depletion by immunoadsorption (IA) could prevent humoral graft injury and thus, in combination with anti-cellular rejection therapy, improve graft survival.

Twenty re-transplanted and broadly immunized cadaver kidney recipients (median PRA reactivity 87%, range 55-100%) were treated with IA (protein A) immediately before transplantation and during the early post-transplantation period (median number of IA sessions 11, range 1-24). Patients received additional prophylactic anti-lymphocyte antibody therapy. Nineteen patients had a negative pre-transplant cross-match. In one patient, a positive cross-match was rendered negative by the pre-transplant IA session.

One-year graft survival was 80% and patient survival 95%. Median (range) serum creatinine in functioning grafts was 1.6 (0.8-2.7) mg/dl at discharge and 1.5 (1.0-5.8) mg/dl at 1 year. Two grafts were lost due to acute vascular rejection, whereby one rejection occurred after withdrawal of immunosuppression due to septicaemia. One patient had acute cellular rejection, which was reversed by a second course of anti-lymphocyte antibody therapy. Thrombotic microangiopathy and surgical complications were the causes for one graft loss each. Retrospective immunohistochemistry revealed peritubular C4d staining, a presumed marker for humoral alloreactivity, in 12 out of 15 biopsies.

These results suggest that prophylactic peri-operative IA and anti-lymphocyte antibody therapy might be an effective therapeutic strategy for the prevention of early graft failure in sensitized re-transplant recipients.

• Silverchair Information Systems
• Ovid Technologies, Inc.