Alloantibody and autoantibody monitoring predicts islet transplantation outcome in human type 1 diabetes.

Long-term clinical outcome of islet transplantation is hampered by the rejection and recurrence of autoimmunity. Accurate monitoring may allow for early detection and treatment of these potentially compromising immune events. Islet transplant outcome was analyzed in 59 consecutive pancreatic islet recipients in whom baseline and de novo posttransplant autoantibodies (GAD antibody, insulinoma-associated protein 2 antigen, zinc transporter type 8 antigen) and donor-specific alloantibodies (DSA) were quantified.

Liver retransplantation in adults: the largest multicenter Italian study.

This study is the largest Italian survey on liver retransplantations (RET). Data report on 167 adult patients who received 2 grafts, 16 who received 3 grafts, and one who received 4 grafts over a 11 yr period.There was no statistically significant difference in graft survival after the first or the second RET (52, 40, and 29% vs 44, 36, and 18% at 1,5,and 10 yr, respectively: Log-Rank test, p = 0.

Description and molecular modeling of a novel human leukocyte antigen allele: A*32:22.

We describe here the sequence and the molecular modeling of a new variant of HLA-A*32 allele officially named A*32:22. This novel allele has been detected in an Italian cord blood sample by sequence-based typing (SBT). The mutation (CAT →CGT), which has occurred at codon 151, at nucleotide position 524, implies an amino acidic change from Histidine to Arginine.

Three novel alleles at the HLA-DRB1 locus identified by sequence-based typing.

We describe here the sequences of 3 new HLA-DRB1 variants officially named DRB1*03:05:03, DRB1*11:10:02, and DRB1*14:86. These novel alleles have been detected in 3 Caucasoid individuals by sequence-based typing. The first and second alleles are the result of a silent mutation, which does not imply any amino acid change.

Heart transplantation with donor-specific antibodies directed toward denatured HLA-A*02:01: a case report.

The development of solid-phase assays for antibody detection has aided in the frequent detection of human leukocyte antigen (HLA) antibodies in nonalloimmunized males. Some scientists have reported that these HLA antibodies are produced to pathogens or allergens and the reactivity with HLA coated beads is the result of cross-reactive epitopes. These antibodies may also be directed toward cryptic epitopes exposed on the denatured beads.

The impact of immunogenetics and clinical factors on the outcome of unrelated cord blood transplantation: the Milano Cord Blood Bank data.

In this article we examined the role of HLA incompatibility, of KIR C1 and C2 ligands and of other clinical factors on 99 cord blood transplants performed using single units from Milano Cord Blood Bank (MICB). We analyzed the occurrence of rejection, overall patient survival (OS) and occurrence of acute GvHD >or= 2 grade (severe aGvHD). No correlation was found between the end points and the number of HLA-A,-B, -DRB1 and -DQB1 mismatches.

Description and molecular modeling of two novel HLA alleles: HLA-A*0343 and A*0345.

We report the identification of two novel human leucocyte antigen (HLA) in two Caucasian individuals. HLA-A*0343 differs from A*03010101 by four changes at nucleotides 411-414 (CCGG-->TGAA) and by a point mutation at position 418 (G-->C). These differences lead to two amino acid substitutions at codon 114, where arginine has changed into negatively charged glutamic acid, and at codon 116, where aspartic acid has changed into positively charged histidine.

Human leukocyte antigen crossmatch testing is important for liver retransplantation.

Although human leukocyte antigen (HLA) crossmatching is often thought to be unnecessary for liver transplants (LTs), we provide evidence that for retransplants, it is essential. Sera from 139 retransplant patients who had received livers from deceased donors were retrospectively analyzed with single antigen beads on a Luminex platform for HLA antibodies. Each patient received at least 2 transplants and was followed up for at least 6 months from the second LT, which was deemed to have failed if the patient had a third LT or died.

A Microsphere-Based Suspension Array for Blood Group Molecular Typing: An Update.

SUMMARY: BACKGROUND: In a previous publication we described a method for Jk(a)/Jk(b), Fy(a)/Fy(b), S/s, K/k, Kp(a)/Kp(b), Js(a)/Js(b), Co(a)/Co(b), and Lu(a)/Lu(b) genotyping based on a microsphere suspension array. Here, an improved version of the assay is presented. METHODS: TWO MULTIPLEX POLYMERASE CHAIN REACTIONS (PCR) WERE DEVELOPED: one for amplification of samples routinely tested and the other for those systems that are tested less frequently.

Isoniazid in patient plasma may cause a false-positive result on the complement-dependent cytotoxicity test.

Correct definition of clinically relevant anti-HLA antibodies is important for transplant organ allocation and outcome. We describe a candidate for kidney transplantation who was treated with isoniazid because of active tuberculosis. The patient's serum gave a positive antibody result on screening with the complement-dependent cytotoxicity (CDC) test but a negative result on screening with a bead-based assay (Luminex).

Clinical relevance of human leukocyte antigen antibodies in kidney transplantation from deceased donors: the North Italy Transplant program approach.

At the North Italy Transplant Program (NITp) Reference Center, which is responsible for pre- and posttransplant immunological evaluation and organ allocation, the sera of patients who enter the kidney waiting list are analyzed with complement dependent cytotoxicity (CDC) and a microbead array technique (Luminex). At present, the NITp waiting list includes 2543 patients. The rate of patients with a percentage panel-reactive antibody (PRA) > or =30 with CDC is about 8%; among them, 1% exhibits a %PRA > or =85.

Killer cell immunoglobulin-like receptor genotype and killer cell immunoglobulin-like receptor-human leukocyte antigen C ligand compatibility affect the severity of hepatitis C virus recurrence after liver transplantation.

In 20% to 30% of infected individuals, hepatitis C virus (HCV) can cause cirrhosis and hepatocellular carcinoma, for which liver transplantation is the best treatment available. HCV re-infection is universal, and hepatitis disease recurrence occurs in most cases with a 30% probability of progression to graft cirrhosis at 5 years post-transplant. The immunological response to HCV involves natural killer (NK) cells and killer cell immunoglobulin-like receptors (KIRs), which specifically recognize human leukocyte antigen (HLA) class I antigens present on target cells.

Blood group genotyping for Jk(a)/Jk(b), Fy(a)/Fy(b), S/s, K/k, Kp(a)/Kp(b), Js(a)/Js(b), Co(a)/Co(b), and Lu(a)/Lu(b) with microarray beads.

Background: Traditionally, blood group typing has been performed with serologic techniques, the classical method being the hemagglutination test. Serotyping, however, may present important limitations such as scarce availability of rare antisera, typing of recently transfused patients, and those with a positive direct antiglobulin test. Consequently, serologic tests are being complemented with molecular methods.

Luminex technology for anti-HLA antibody screening: evaluation of performance and of impact on laboratory routine.

The recent introduction of new technologies such as Luminex has provided alternative methods to the Complement Dependent Cytotoxicity (CDC) test for HLA specific antibody detection. In this study we compared the results obtained with CDC to those obtained using a Luminex method with the aim of evaluating the impact of this new technology on antibody screening policies in our transplant setting.A total of 1,421 sera, acquired from patients on the waiting list for a kidney transplant or following transplantation, were tested by both methodologies.

Complete sequencing of the HLA-A*68020102 novel allele identified in two Caucasoid families.

We describe here the isolation and the full-length sequence of the coding region of the HLA new variant at the HLA-A locus officially named A*68020102. This variant shows an 11 base pairs deletion within the 5' UTR region. The exon sequence is identical to that of A*6802 and the commercially available anti-A68 typing sera react with the antigen coded by the allele A*68020102.

Incidence of second primary cancer in transplanted patients.

Background: Solid organ transplanted patients have a three- to fourfold higher lifetime risk of developing a cancer than the general population. However, the incidence of a second primary cancer in transplanted patients has never been studied, despite the fact that the presence of regular follow-ups and the increased survival of these patients make them a very attractive model.

Methods: We investigated the incidence of a second primary cancer (SPC) in 7,636 patients who underwent a kidney, liver, lung or heart transplant between 1970 and 2004, and were followed-up for 51,819 person-years.

Split and whole liver transplantation outcomes: a comparative cohort study.

A specific split liver transplantation (SLT) program has been pursued in the North Italian Transplant program (NITp) since November 1997. After 5 yr, 1,449 liver transplants were performed in 7 transplant centers, using 1,304 cadaveric donors. Whole liver transplantation (WLT) and SLT were performed in 1,126 and 323 cases, respectively.

HLA-DRB1 donor-recipient mismatch affects the outcome of hepatitis C disease recurrence after liver transplantation.

Background & Aims: This study extends our previously reported observations that various immunological factors are associated with the occurrence of histologically proven recurrent hepatitis C. The two specific issues investigated were to confirm the associations of MHC alleles and donor/recipient mismatch with the occurrence of recurrent hepatitis C in an independent cohort of newly transplanted patients and to look for immunologic and nonimmunologic variables affecting the severity of the recurrent disease.

Methods: Two separate cohorts of consecutive patients were studied: a look-back cohort (LC) of 120 patients and a cohort for studying the disease progression (CSDP) of 190 patients.

Long-term outcome of renal transplantation from older donors.

Background: Long-term survival of kidney grafts from older donors is inferior to that of grafts from younger donors. We sought to determine whether selecting older kidneys according to their histologic characteristics before implantation would positively influence long-term outcome.

Methods: In a prospective cohort study, we assessed outcomes among 62 patients who received one or two histologically evaluated kidneys from donors older than 60 years of age.

Kidney transplantation from anti-HBc+ donors: results from a retrospective Italian study.

Background: The risk of transmitting a hepatitis B virus (HBV) infection from donor kidneys with a past HBV serological profile may be negligible. Data on HBV transmission to kidney transplant recipients from donor organs that were anti-HBc/HBsAg in Italy has not been previously reported. Anti-HBc testing in cadaver organ donors has been mandatory in Italy since 2002, when anti-HBc determinations were included in the National Guidelines for donor evaluation.

Pharmacokinetic of cyclosporine microemulsion in pediatric kidney recipients receiving A quadruple immunosuppressive regimen: the value of C2 blood levels.

Background: The management of cyclosporine therapy in pediatric kidney-transplant recipients is largely based on single center's experience rather than on a univocal pharmacokinetic approach based on therapeutic drug monitoring. A prospective multicenter trial was designed to address the question whether C2 blood level monitoring of cyclosporine microemulsion therapy is feasible in the pediatric setting.

Methods: Sixty-four pediatric kidney-transplant recipients receiving a triple immunosuppressive regimen based on cyclosporine microemulsion had their cyclosporine dose adjusted to the same protocol-defined C2 targets from the time of the transplant until 2 years posttransplant.

Split-liver transplantation with pediatric donors: a multicenter experience.

Background: Outcomes of split-liver transplantation (SLT) with pediatric donors have never been specifically reported.

Methods: A prospective multicenter study on SLT using donors younger than 15 years was conducted. Thirty-nine split-liver procedures generating a left lateral segment (LLS) and an extended right graft (ERG) were performed.

One-year results of basiliximab induction and tacrolimus associated with sequential steroid and MMF treatment in pediatric kidney transplant recipient.

We report the 1-year results with a triple immunosuppressive regimen in pediatric recipients of a first kidney transplant, in order to evaluate its safety and efficacy in the prevention of acute rejection and in the reduction of steroid side effects. The immunosuppression is as follows: (i) basiliximab (20 mg if body weight >30 kg; 10 mg if < 30 kg) is given pretransplant and at day 4; (ii) tacrolimus (Tac) is administered in order to obtain blood trough levels of 10-20 and 5-10 ng/ml during and after the first 2 months post-transplant, respectively; (iii) steroids are tapered during the first 6 months and then replaced by mycophenolate mofetil (depending on previous rejection episodes, infection status and the result of a routine biopsy) at a dosage of 4-600 mg/m(2) body surface area. Fifty-three children (median age 13 years, range 2-20) have entered this protocol.