Search

Background and objectives Transfusion-related acute lung injury ( TRALI) is the leading cause of transfusion-related mortality. To support the diagnosis of antibody-mediated TRALI, HLA and HNA antibodies are tested in involved blood donors. Identification of antibody positive donors is important as exclusion of these donors is part of preventative strategies against TRALI. We compared cellular-based versus bead-based techniques for diagnosis of antibody-mediated TRALI. Materials and methods All reported TRALI cases in the Netherlands during a 5-year period were evaluated. Donors were screened for the presence of HLA class I and class II antibodies using both cellular-based and bead-based techniques. Results In total, 100 TRALI cases were reported of which 91 were fully tested. In 113 donors, HLA antibodies were detected of which 84 were only detected by bead-based techniques, 12 only by cellular-based tests and 17 by both assays. Antibody-mediated TRALI was diagnosed in 44 of 91 reported cases. Twenty-one (48%) of these cases would not have been identified using only cellular-based assays. Conclusion Bead-based techniques show a higher sensitivity for detecting incompatible donors in TRALI cases than cellular-based assays. These results suggest that the use of bead-based assays will result in a significant reduction of future TRALI reactions as more antibody positive donors will be excluded from future donations. [ABSTRACT FROM AUTHOR]

We evaluated inhibitor formation in a group of patients with mild haemophilia A caused by an Arg593 to Cys mutation. A remarkably high cumulative inhibitor incidence of 14% over 22 years was observed. Three of 49 patients developed transient, low-titre inhibitors, which remained below 2.0 BU mL−1. Four patients with an Arg593 to Cys mutation developed high-titre inhibitors (>5.0 BU mL−1). Three of these patients have been described previously. In this study, we characterized inhibitory antibodies in a fourth patient with high-titre inhibitors. Epitope mapping studies revealed that antibodies were predominantly directed to the A2 domain of factor VIII. We addressed the role of human leucocyte antigen (HLA) class II alleles in inhibitor development in patients with an Arg593 to Cys mutation by HLA genotyping. In the group of inhibitor patients raised frequencies of HLA-DRB1*01 and HLA-DQB1*05 were observed that did not reached statistical significance. Our data suggest that inhibitor development in mild haemophilia A patients with an Arg593 to Cys mutation is not linked to HLA class II profile. [ABSTRACT FROM AUTHOR]

We have previously demonstrated an HLA-A * 0101null allele segregating in a family with the HLA-B8, - Cw7, - DR3, - DR52, - DQ2 haplotype. In the present study the regulatory elements with known transcription enhancement activity of the silenced HLA-A * 0101 allele were analyzed. In the enhancer B element, a T was substituted for a C at position – 106, whereas no other alterations were found in the adjacent 5′ section of the HLA-A * 0101null allele. This substitution was not seen in the enhancer B elements of the corresponding genes involved in normal HLA-A * 0101 membrane expression. Comparison of enhancer B element sequences of classical functional major histocompatibility complex ( MHC) class I alleles demonstrated a high degree of conservation. In contrast, many MHC class I pseudogenes showed mutation in their enhancer B boxes. These results may indicate that the single mutation detected in the enhancer B element plays a pivotal role in the abolishment of membrane expression of the HLA-A * 0101null allele. [ABSTRACT FROM AUTHOR]

For several haematological malignancies, allogeneic stem cell transplantation is the treatment of choice. In most cases an HLA-identical sibling is required. If the mother of a patient is pregnant, cord blood from a related donor, which can be used for stem cell transplantation, might be obtainable in the near future. For the patient, knowledge of the foetal HLA-type can be important since it might influence choice of treatment and timing of transplantation. If the foetus is HLA compatible, as would be the situation in 25% of cases, the delivery has to be arranged in such a way that cord stem cells can be collected. As a result, in the other 75% of cases (spontaneous) delivery can take place in the home/local setting. Here we report four cases in which amniocentesis was performed and HLA-typing influenced treatment of the patient and delivery of the sibling. Bone Marrow Transplantation (2000) 25, 579–581. [ABSTRACT FROM AUTHOR]

The presence of donor-specific anti-HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long-term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement-dependent crossmatch. In living donor transplants, we found a limited effect on graft survival of DSAs against class I or II antigens after transplant. Class I and II DSAs combined resulted in decreased 10-year graft survival (84% to 75%). In contrast, after deceased donor transplant, patients with class I or class II DSAs had a 10-year graft survival of 59% and 60%, respectively, both significantly lower than the survival for patients without DSAs (76%). The combination of class I and II DSAs resulted in a 10-year survival of 54% in deceased donor transplants. In conclusion, class I and II DSAs are a clear risk factor for graft loss in deceased donor transplants, while in living donor transplants, class I and II DSAs seem to be associated with an increased risk for graft failure, but this could not be assessed due to their low prevalence., (© 2018 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Kidney transplantation is the best treatment option for patients with end-stage renal failure. At present, approximately 800 Dutch patients are registered on the active waiting list of Eurotransplant. The waiting time in the Netherlands for a kidney from a deceased donor is on average between 3 and 4 years. During this period, patients are fully dependent on dialysis, which replaces only partly the renal function, whereas the quality of life is limited. Mortality among patients on the waiting list is high. In order to increase the number of kidney donors, several initiatives have been undertaken by the Dutch Kidney Foundation including national calls for donor registration and providing information on organ donation and kidney transplantation. The aim of the national PROCARE consortium is to develop improved matching algorithms that will lead to a prolonged survival of transplanted donor kidneys and a reduced HLA immunization. The latter will positively affect the waiting time for a retransplantation. The present algorithm for allocation is among others based on matching for HLA antigens, which were originally defined by antibodies using serological typing techniques. However, several studies suggest that this algorithm needs adaptation and that other immune parameters which are currently not included may assist in improving graft survival rates. We will employ a multicenter-based evaluation on 5429 patients transplanted between 1995 and 2005 in the Netherlands. The association between key clinical endpoints and selected laboratory defined parameters will be examined, including Luminex-defined HLA antibody specificities, T and B cell epitopes recognized on the mismatched HLA antigens, non-HLA antibodies, and also polymorphisms in complement and Fc receptors functionally associated with effector functions of anti-graft antibodies. From these data, key parameters determining the success of kidney transplantation will be identified which will lead to the identification of additional parameters to be included in future matching algorithms aiming to extend survival of transplanted kidneys and to diminish HLA immunization. Computer simulation studies will reveal the number of patients having a direct benefit from improved matching, the effect on shortening of the waiting list, and the decrease in waiting time., (Copyright © 2014. Published by Elsevier B.V.)

Objective: Studies in Southeast Asia showed that HLA-B*2704 is positively associated with spondyloarthropathy (SpA), while B*2706 does not occur in such patients. In view of the absence of an association between B*2706 and SpA it was suggested that B*2706 protects against the disease, while it is supposed that B*2704 presents pathogenetic peptides. We studied families in which both B*2704 and B*2706 occurred to see whether in B*2704/B*2706 heterozygotes the effect of one of the subtypes shows a preponderance over the other., Methods: Two families of mixed Chinese/Indonesian origin were studied. HLA-B27 subtyping was performed by polymerase chain reaction in combination with sequence specific oligonucleotide probes., Results: In one family, members with B*2704, B*2706, or both occurred. In the other family B*2704, B*2706, and B*2708 were present. In both families SpA was seen only in B*2704 positive members, while the B*2706 and B*2708 positive members were healthy, except some B*2704/B*2706 or B*2704/B2708 heterozygotes., Conclusion: The pathogenic influence of B*2704 is thus dominant over the supposed protective influence of B*2706. It is probable that B*2704 can present pathogenetic peptides, while a protective influence of B*2706 does not exist. B*2708, which was until now described in only a few cases, behaved in this study as B*2706 and is probably not associated with SpA.

Background: The aim of the present study was to analyze the effect of HLA-DRB1* mismatches on graft function and graft survival in 92 patients who received serologically HLA-DR split antigen-matched cadaveric renal transplants., Methods: The polymorphic second exon of the HLA-DRB1 alleles was typed using the sequence-specific oligonucleotides technique., Results: The results show that in 26 of the 92 analyzed combinations, one or more HLA-DRB1* mismatches were found (28%). The analysis of the occurrence of treatable rejection episodes during the first 3 months after transplantation demonstrated a significantly higher incidence of rejection episodes in the HLA-DRB1*-mismatched group: 18 of 26 (69%) in the HLA-DRB1*-mismatched group against 23 of 66 (35%) in the HLA-DRB1*-matched group (P(uncorr)=0.0033). However, no effect of HLA-DRB1* mismatches on graft survival was found, although in general graft survival in the whole patient group was negatively influenced by the occurrence of rejection episodes during the first 3 months after transplantation (P(uncorr)=0.0008). In contrast, in the HLA-DR4-matched donor-recipient combinations (n=28), the effect of mismatching for the HLA-DRB1*04 alleles seemed to have a pronounced effect not only on the occurrence of rejection episodes but also in the form of diminished graft survival., Conclusions: Thus, this study indicates that the existence of HLA-DRB1* allele mismatches in renal transplant recipients, matched for the serologically defined HLA-DR split antigens, is not harmful for the transplant. The exception is the HLA-DRB1*04 mismatch, which seems to be deleterious for the grafted organ.

Objective: Eleven subtypes of HLA-B27 have been identified. If some of these subtypes had a stronger association with spondyloarthropathy (SpA) than others, this might tell us which peptides are of pathogenetic importance. A subtype preponderance has not been proved in Caucasians or in Asian Indians. Our objective was to determine whether some subtypes are positively or negatively associated with SpA in Indonesia., Methods: Cells of 34 HLA-B27 positive patients with SpA (fulfilling the European Spondylarthropathy Study Group criteria) and 26 HLA-B27 positive controls, all living in Java, Indonesia, were sampled. Patients and controls were divided according to their presumed ethnic origin. HLA-B27 subtyping (B*2701-09) was performed by polymerase chain reaction in combination with sequence specific oligonucleotide probes to analyze polymorphism in exons 2 and 3 of HLA-B27., Results: HLA-B*2701, *2702, *2703, *2708, and *2709 were found in neither group. HLA-B*2704 was found in 23/34 (68%) of the patients and in only 4/26 (15%) of the controls (p < 0.01). HLA-B*2706 was found in none of the 34 patients, but in 21/26 (81%) of the controls (p < 0.01). One drawback of the study was that most patients were of Chinese descent and most controls were native Javanese. Nevertheless, the absence of SpA among HLA-B*2706 positive individuals is noteworthy., Conclusion: HLA-B*2704 is positively associated with SpA (RR = 11.5), while *2706 is negatively associated with this disease (RR < 0.007). The results confirm the findings of Lopez-Larrea, et al in Thailand.

We have characterized HLA incompatibilities in a group of 16 B44-positive patients who were serologically ABDR matched with their 23 (unrelated) potential bone marrow donors. After analysis with a combination of cellular techniques, IEF for HLA-A/B and oligotyping for class II and HLA-B44, 44% of the patients revealed one or more HLA incompatibility with at least one of their potential donors. CTL activity was detected in 12 of the 22 combinations tested. CTL incompatibility occurred more frequently in DR subtype-mismatched combinations, but CTL reactivity was always directed against class I. To characterize these incompatibilities between matched unrelated individuals, we analyzed the specificity of T-cell clones from seven primary CTL cultures. In three combinations, CTL reactivity was directed against a subtype of B44. In two combinations, the CTL reactivity was directed against a non-B44 class I subtype. In two of seven combinations, the CTLs recognized an antigen that, though unconditionally associated with B4403, was expressed by 60% of the B4403+ cells only. Because all 12 of these B4403+ targets recognized could be typed for one HLA-C allele only (Cwl-Cw8), we believe that this alloreactivity might be directed against a serologically undefined Cw antigen.

HLA-DRw53 is a supertypic specificity expressed by HLA-DR4-, HLA-DR7-, and HLA-DR9-positive cells. In the present study, the fine specificity of an HLA-DRw53-specific alloantiserum (MSD-51) was analyzed in serology and by the isoelectric focusing technique. In serology, MSD-51 recognized HLA-DRw53-positive cells with the exception of cells expressing the HLA-DR7/DRw53/DQw9 haplotype. The immunoprecipitation studies and the use of the IgM-reducing agent dithiothreitol revealed that MSD-51 consisted of at least two antibodies: (1) an IgM antibody which reacted with the HLA-DRB4 gene product of HLA-DRw53-positive cells, except HLA-DR7/DRw53/DQw9-expressing cells, and (2) at least one IgG antibody which recognized a linear sequence or conformational structure formed by positions 67 to 70 on the HLA-DRB1 gene product of HLA-DR4- and HLA-DR9-positive cells. These findings demonstrate the complexity of the supertypic HLA-DRw53 antigen analyzed with a serologically well-defined HLA-DRw53-specific alloantiserum.

The antigens belonging to the HLA-A10 group, HLA-A25, -A26, -Aw34, and -Aw66, have been characterized serologically during the International Histocompatibility Workshops. However, it remains difficult to discriminate between the HLA-A26 antigen on the one hand and the HLA-Aw34 and -Aw66 antigens on the other on the basis of serology. In this paper, we compare the serologically defined antigens with the data obtained by one-dimensional isoelectric focusing. The results indicate that the serologically well-defined HLA-A25 antigen cannot be discriminated from the HLA-A26 antigen by one-dimensional isoelectric focusing. In contrast, this technique can indeed be used to discriminate between HLA-A26, -Aw34 and -Aw66 antigens. In addition, the biochemical analysis suggests further heterogeneity of the HLA-Aw34 antigen. This antigen can be subdivided into three variants.