Human Leucocyte Antigen Sensitisation and Its Impact on Transfusion Practice.

Human leucocyte antigen (HLA) sensitisation, including the formation of antibodies against HLA, can cause serious effects in patients receiving blood. Under certain circumstances, donor HLA antibodies in the blood product can trigger the patient's granulocytes to release mediators that cause transfusion-associated lung injury (TRALI), a serious complication of transfusion. The HLA systems of both donor and patient are involved in transfusion-associated graft-versus-host disease, which is a rare disease with a high mortality.

Alpha-synuclein levels in blood plasma decline with healthy aging.

There is unequivocal evidence that alpha-synuclein plays a pivotal pathophysiological role in neurodegenerative diseases, and in particular in synucleinopathies. These disorders present with a variable extent of cognitive impairment and alpha-synuclein is being explored as a biomarker in CSF, blood serum and plasma. Considering key events of aging that include proteostasis, alpha-synuclein may not only be useful as a marker for differential diagnosis but also for aging per se.

The complement-mediated prozone effect in the Luminex single-antigen bead assay and its impact on HLA antibody determination in patient sera.

The Luminex xMAP system has become an important tool for HLA antibody screening and identification in sera of transplant patients. Recently, the Luminex single antigen bead assay was shown to be prone to an artefact, the so called prozone phenomenon: Sera with high titer HLA antibodies gave negative results when tested neat, but reacted strongly positive after 1:10 dilution. We also observed such a phenomenon and found that it was most likely caused by the complement component 1 (C1) by competitively displacing the detection antibodies.

HLA antibody specification using single-antigen beads--a technical solution for the prozone effect.

Background: Substantial progress in human leukocyte antigen antibody specification has been made by the introduction of Luminex single-antigen bead (SAB) assays. This progress was impaired when it turned out that this method is prone to a prozone effect leading to false-negative results in the case of high antibody titers. Testing serum and ethylenediaminetetraacetic acid (EDTA) plasma of one patient in parallel, we observed the prozone effect with the serum sample only.

Expression of blood group genes by mesenchymal stem cells.

Incompatible blood group antigens are highly immunogenic and can cause graft rejections. Focusing on distinct carbohydrate- and protein-based membrane structures, defined by blood group antigens, we investigated human bone marrow-derived mesenchymal stem cells (MSCs) cultured in human serum. The presence of H (CD173), ABO, RhD, RhCE, RhAG, Kell, urea transporter type B (SLC14A1, previously known as JK), and Duffy antigen receptor of chemokines (DARC) was evaluated at the levels of genome, transcriptome and antigen.

Functional dissociations in top-down control dependent neural repetition priming.

Little is known about the neural mechanisms underlying top-down control of repetition priming. Here, we use functional brain imaging to investigate these mechanisms. Study and repetition tasks used a natural/man-made forced choice task.

Successful haematopoietic stem cell transplantation from a matched unrelated donor following three graft failures from HLA-mismatched related donors.

Graft rejection and graft failure are serious complications after allogeneic stem cell transplantation (SCT). We report a patient with CML in first chronic phase who finally engrafted with a transplant from an HLA-identical unrelated donor after graft failures from two related HLA-mismatched sibling donors. After failure of one BM and two PBSC grafts from two 1 HLA-antigen mismatched related donors, the patient was finally successfully transplanted from a subsequently identified HLA-identical unrelated donor (donor 3).

Successful transplantation of highly selected CD34+ peripheral blood stem cells in a HLA-sensitized patient treated with immunoadsorption onto protein A.

Background: Haploidentical bone marrow transplantation with preexisting anti-HLA antibodies is associated with a high risk of graft failure.

Methods: A 27-year-old female patient with chronic myeloid leukemia and evidence of several osseous chloromas had no suitable matched bone marrow donor, and fluorescence cytometric cross-match (FCXM) revealed antibodies against donor-specific HLA-molecules. Immunoadsorption onto staphylococcal protein A was applied to remove these antibodies, and peripheral stem cell transplantation was performed from her haploidentical sister after a negative FCXM was documented after immunoadsorption and conditioning treatment.

Platelet-specific antibodies in female blood donors after pregnancy.

Sera of 500 female blood donors after pregnancy were tested for platelet-specific antibodies (HPA-1, 3, 5) using the MAIPA assay. Twenty-one sera (4.2%) were found to be positive: four anti-HPA-1a, one anti-HPA-5a and 16 anti-HPA-5b.

Platelet antibodies in patients with migraine.

The reported decrease of platelet serotonin receptors in patients with migraine could be due to an autoimmune reaction. We therefore, examined sera from 42 migraineurs without aura, 26 migraineurs with aura, and 107 headache-free blood donors for platelet-reactive antibodies using the platelet adhesion immunofluorescence test, the NIH-lymphocytotoxicity test, and the monoclonal antibody-specific immobilization of platelet antigens test. IgG antibodies against non-HLA class I platelet antigens were found in 9.

Limits of the MAIPA assay when differentiating high-titered platelet-reactive antibodies.

Experience with the MAIPA assay for the diagnosis of platelet-reactive antibodies has shown that high-titered antibodies falsify the test results. We here demonstrate 2 cases: i) A serum with high-titered HLA antibodies (100% panel reactivity in the LCT, titer between 4,000 and 12,000), and ii) Serum with a high-titered anti-HPA-1a (titer in the MAIPA assay 1,000). In both cases, it can be demonstrated that these antibodies led to unspecific reactions.

Frequency and specificity of platelet-specific alloantibodies in HLA-immunized haematologic-oncologic patients.

The frequency and specificity of platelet-alloantibodies to human platelet antigens (HPA) -1, -3 and -5 was investigated in 59 multitransfused, HLA-immunized patients. Using the MAIPA test (monoclonal antibody specific immobilization of platelet antigens) platelet alloantibodies could be demonstrated in 10 (17%) patients. In one patient the antibody was present prior to any transfusions and probably induced by multiple previous pregnancies.

[Severe neonatal alloimmune thrombocytopenia with delayed antibody detection].

Neonatal alloimmune thrombocytopenia (NAIT) is caused by maternal immunisation against a paternal antigen on fetal platelets. The antigen involved in the majority of cases is HPA-1 a (PIA1). Usually circulating platelet alloantibodies are detectable in the mother.

Reactivation of recipient antibody to blood cell antigens soon after allogeneic bone marrow transplantation.

Reactivation of recipient antibody to HLA and red blood cell antigens is described in 8 patients after allogeneic bone marrow transplantation. These IgG antibodies can be detected between day 10 and day 40 after transplantation and, in 1 patient, can be shown to be antigen-independent. We hypothesize that, induced by graft recognition of recipient antigens, antigen-independent activation of sensitized recipient B cells takes place leading to transient antibody production.

[Diagnosis and therapy of fetal alloimmune thrombocytopenia].

In fetal alloimmune thrombocytopenia, maternal IgG antibodies directed against platelets pass into the fetal circulation and lead to the destruction of fetal platelets. Fetal thrombocytopenia is usually first noted postnatally, but the maternal alloantibodies may lead to severe fetal haemorrhage in utero in the second or, more commonly, third trimester. Platelet-specific antibodies appear to play the major role in the pathogenesis of fetal alloimmune thrombocytopenia.

Reactivation of antibodies of donor and recipient origin to platelet antigens early after allogeneic bone marrow transplantation: a case report.

Reactivation of platelet-reactive antibodies of donor and recipient origin is described in a patient following allogeneic BMT (donor: anti-HPA-5b; recipient: anti-HLA, anti-HPA-1b). The antibodies were detected around day 15 after BMT, peaked around day 25, and then decreased. These antibodies are interpreted as an antigen-independent reactivation of secondary B-cell responses, activated in the context of recognition of host antigens by the graft.

[Demonstration of platelet-specific alloantibodies in HLA-sensitized hematologic oncologic patients].

Alloimmunization to the platelet-specific antigen systems HPA-1, -3 and -5 was studied in 59 multitransfused patients (31 females, 16 males, 12 children) with haematologic-oncologic disorders. All patients tested had broad-reacting or multispecific HLA antibodies. Of these, 10 (17%) were found to have additional platelet-specific alloantibodies.

Difficulties in the antenatal assessment of neonatal alloimmune thrombocytopenia.

In this paper we present a patient with an initially questionable history of neonatal alloimmune thrombocytopenia (NAT) due to materno-fetal HPA-1a (PLA1) incompatibility. No circulating antibodies were detectable in untreated maternal serum, but an adsorption/elution technique enabled the demonstration of the platelet-specific anti-HPA-1a (anti-PLA1) in maternal serum. Cordocentesis at 35 weeks of gestation revealed a fetal platelet count of 18 x 10(9)/l.

Serological screening, using three different test systems of platelet-transfused patients with hematologic-oncologic disorders.

Sera of hematologic-oncologic patients were tested regularly after platelet transfusions in three test systems: lymphocytotoxicity test, platelet adhesion immunofluorescence test, and--only selected sera--in the monoclonal antibody-specific immobilization of platelet antigen test. Of 388 patients 53 (14%) had HLA antibodies 5 of these in combination with platelet-specific alloantibodies. Lymphocyte-restricted (non-HLA) reactions were observed in 20 patients, the majority of which was attributed to lymphocyte-specific auto- or alloantibodies.