Peter Schlenke

• Professor
• Medical University of Graz

Type 1 and type 2 diabetes are associated with increased severity and mortality from respiratory virus infections, including SARS-CoV-2. Vaccination in the general population significantly reduces the risk of severe respiratory viral infection and triggers a strong, polyfunctional and lasting T cell response in healthy individuals. However, vaccine...

Zusammenfassung Zielsetzung Die Pathogeninaktivierung (PI) ist ein weltweit anerkanntes Verfahren zur Verbesserung der Sicherheit von Thrombozytenkonzentraten und Plasma. Diese Arbeit untersucht die Notwendigkeit und potenziellen Vorteile der Implementierung der PI für Thrombozytenkonzentrate in Deutschland. Methodik Analysiert werden sowohl Daten...

Background: There is a narrow therapeutic window for immunosuppression using calcineurin inhibitors. Drug trough levels do not reflect immunosuppression and should be replaced by pharmacodynamic monitoring. This prospective cohort study was designed to evaluate the effect of an extended-release formulation of tacrolimus (LCP Tac) on the nuclear fac...

Characterization of three novel HLA class I alleles by next generation sequencing.

Background Determining serum 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D [24,25(OH)2D] and the vitamin D metabolite ratio (VMR) allows the identification of individuals with a low vitamin D metabolite profile. Here, we evaluated if such a functional approach provides superior diagnostic information to serum 25(OH)D alone. Methods 25(OH...

B-cell depleting therapies result in diminished humoral immunity following vaccination against COVID-19, but our understanding on the impact on cellular immune responses is limited. Here, we performed a detailed analysis of cellular immunity following mRNA vaccination in patients receiving B-cell depleting therapy using ELISpot assay and flow cytom...

Background: The application of blood concentrates has gained popularity in dentistry in recent years. Platelet-rich fibrin (PRF) has been discussed frequently due to a high content of growth factors and the option of chair-side manufacturing in a simple centrifugation process. PRF is free from adjuvants and inexpensive to produce. The number of st...

Introduction: Regular whole blood donors often suffer from iron deficiency (ID) or iron deficiency anemia due to the loss of 200-300 mg of iron with each donation. Hemoglobin (Hb) as donor eligibility criterion reflects iron stores only poorly. ID in blood donors is typically prevented or treated with orally administered ferrous salts, which frequ...

Our group recently reported enhanced erythroid differentiation from human iPSC by closer mimicry of physiological cell contacts in a three dimensional network, termed „haematopoietic cell forming complex“ (HCFC)1. From this HCFC, CD43+ hematopoietic cells (purity >95 %) were continuously released into the culture supernatant. Characterization of th...

We performed reprogramming of human erythroblasts derived from CD34+ hematopoietic stem / progenitor cells of a healthy donor. CD34+ cells were differentiated in-vitro into a pure population of CD36⁺ erythroblasts and nucleofected with four episomal plasmids expressing SOX2, OCT3/4, KLF4, LIN28, L-MYC and TP53-shRNA. The established iPSC line showe...

Aim: The purpose of this study was to obtain data concerning growth factor release within liquid and solid platelet-rich fibrin (PRF) matrices and to estimate the amount of potential interindividual variations as a basis for further preclinical and clinical trials. Therefore, we aimed to determine possible differences in the release of growth facto...

Modern medicine increases the demand for safe blood products. Ex vivo cultured red blood cells (cRBC) are eagerly awaited as a standardized, safe source of RBC. Established culture models still lack the terminal cytoskeletal remodeling from reticulocyte to erythrocyte with changes in the biomechanical properties and interacts with membrane stiffnes...

Cultured red blood cells from human induced pluripotent stem cells (cRBC_iPSCs) are a promising source for future concepts in transfusion medicine. Before cRBC_iPSCs will have entrance into clinical or laboratory use, their functional properties and safety have to be carefully validated. Due to the limitations of established culture systems, such s...

Individuals with ABO type O, naturally possessing anti-A and anti-B antibodies in their serum, are underrepresented among patients infected with SARS-CoV-2 compared with healthy controls. The ABO antibodies might play a role in the viral transmission. Therefore, we aimed to quantify anti-A/anti-B, including their subclasses IgM, IgG and IgA, in the...

Cryoprecipitate is a plasma-derived blood product, enriched for fibrinogen, factor VIII, factor XIII, and von Willebrand factor. Due to infectious risk, the use of cryoprecipitate in Central Europe diminished over the last decades. However, after the introduction of various pathogen-reduction technologies for plasma, cryoprecipitate production in b...

Background Rheumatoid arthritis (RA) is a systemic autoimmune disease leading to erosive joint destruction. Although the exact pathogenesis is still elusive, the strong association of certain HLA class II molecules, such as HLA-DRB1*0401 (HLA-DR4), suggest involvement of CD4 ⁺ T cells (1,2). Mouse models of RA mimic specific aspects of the disease...

Context.– Serological tests on automated immunology analyzers are increasingly used to monitor the acquired immunity against SARS-CoV-2. The heterogeneity of assays raises concerns about their diagnostic performance and comparability. Objective.– To test sera from formerly infected individuals for SARS-Cov-2 antibodies utilizing six automated sero...

HLA-B*51:01:01:78 and the extended confirmatory sequence of HLA-B*18:01:26 were identified by next generation sequencing. This article is protected by copyright. All rights reserved.

Aims: Immune response to COVID-19 vaccination and a potential impact of glycaemia on antibody levels in people with diabetes remains unclear. We investigated the seroconversion following first and second COVID-19 vaccination in people with type 1 and type 2 diabetes in relation to glycaemic control prior to vaccination and analysed the response in...

Immunocompromised patients are considered high-risk and prioritized for vaccination against COVID-19. We aimed to analyze B-cell subsets in these patients to identify potential predictors of humoral vaccination response. Patients (n=120) suffering from hematologic malignancies or other causes of immunodeficiency and healthy controls (n=79) received...

Background This study aimed to quantify the potential survival benefit of convalescent plasma therapy (CVP) in critically ill patients with acute respiratory failure related to coronavirus disease-2019 (COVID-19). Methods This is a single-center prospective observational cohort study in COVID-19 patients with acute respiratory failure. Immediately...

Aims: Immune response to COVID-19 vaccination and a potential impact of glycaemia on antibody levels in people with diabetes remains unclear. We investigated the seroconversion following first and second COVID-19 vaccination in people with type 1 and type 2 diabetes in relation to glycaemic control prior to vaccination and analysed the response in...

Introduction: Recurrent mutations in calreticulin (CALR) are present in 70% to 80% of essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients without a JAK2 or MPL mutation. Despite recent advances in understanding mutant CALR, the detailed mechanisms are not fully elucidated, and current knowledge is mainly based on transgenic mous...

Introduction: Acute Myeloid Leukemia (AML) is a malignant disease of the bone marrow that can arise from a premalignant condition called clonal hematopoiesis of indeterminate potential (CHIP). Mutations in Serine and Arginine-rich Splicing Factor 2 (SRSF2) are detected in CHIP and mediate a high risk for AML development. Here we used CRISPR/Cas9-me...

Melanomas are aggressive tumors with a high metastatic potential and an increasing incidence rate. They are known for their heterogeneity and propensity to easily develop therapy-resistance. Nowadays they are one of the most common cancers diagnosed during pregnancy. Due to the difficulty in balancing maternal needs and foetal safety, melanoma is c...

HLA‐C*03:03:01:52N differs from HLA‐C*03:03:01:01 by one nucleotide substitution at position gDNA 202 (A>G) in Intron1 This article is protected by copyright. All rights reserved.

Objectives Immunocompromised patients are at risk of severe coronavirus disease 2019 and are considered a high priority for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Humoral vaccination response is impaired in these patients when circulating B cells are lacking. We aimed to analyze B-cell subsets at the time of vacci...

Ex vivo cultured red blood cells (cRBC) are a promising resource for future safe blood products, independent of voluntary blood donations. Since terminal maturation to biconcavity is still lacking ex vivo, understanding the relationship between shape, structure and function is essential for future applications. This study aimed to investigate the t...

Background The ABO blood group system has been previously discussed as a risk factor to develop, as well as a prognostic factor in non-metastatic renal cell carcinoma (RCC). Controversial findings have been reported in different populations of RCC patients with rather short follow-up periods. In this study, we aimed to clarify the distribution and...

HLA-C*07:02:01:115 differs from C*07:02:01:03 by one nucleotide substitution at position gDNA -243 in 5’UTR This article is protected by copyright. All rights reserved.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets the respiratory and gastric epithelium, causing coronavirus disease 2019 (COVID-19). Tissue antigen expression variations influence host susceptibility to many infections. This study aimed to investigate the closely linked Lewis (FUT3) and ABO histo-blood types, includi...

HLA‐C*14:124 differs from C*14:02:01:01 by one nucleotide substitution at position 757 in exon 4. This article is protected by copyright. All rights reserved.

Ex vivo-generated red blood cells are a promising resource for future safe blood products, manufactured independently of voluntary blood donations. The physiological process of terminal maturation from spheroid reticulocytes to biconcave erythrocytes has not been accomplished yet. A better biomechanical characterization of cultured red blood cells...

Background: The development of allo-anti-Rh17 (anti-Hr0) in a -D- phenotype whose red blood cells (RBCs) lack CcEe antigens is most likely triggered by transfusion, transplantation, or pregnancy. Gene conversion is the predominating factor in generating RHD-CE-D and RHCE-D-CE hybrids like -D-. Methods: We report here immunohematological and obst...

Most of the current knowledge on Burkholderia pseudomallei-induced inflammasome activation and cell death in macrophages is derived from murine systems. Little is known about the involved bacterial structures and mechanisms in primary human macrophages. This is of particular relevance since murine and human macrophages as well as primary cells and...

Background Pathogen reduction (PR) of platelet concentrates (PCs) contributes to the safety of platelet (PLT) transfusion by reducing the risk of transfusion‐transmitted infections and transfusion‐associated graft‐versus‐host disease. In vitro quality of pathogen‐reduced double‐dose PC (PR‐PC) made of eight whole blood (WB)‐derived buffy coats (BCs...

Since the emergence of SARS-CoV-2 numerous antibody assays have become available, demonstrating different performance characteristics. This study focused on a quantitative correlation between different commercial assays and a neutralization test (NT). Comparative data is needed as a basis for the production of convalescent plasma and potential inte...

Background: Besides anemia, iron deficiency may cause more subtle symptoms, including the restless legs syndrome (RLS), the chronic fatigue syndrome (CFS) or sleeping disorders. Objective: The aim of this pre-planned secondary analysis of the IronWoMan randomized controlled trial (RCT) was to compare the frequency and severity of symptoms associate...

Background: Besides anemia, iron deficiency may cause more subtle symptoms including those of the restless legs syndrome (RLS), the chronic fatigue syndrome (CFS) or sleeping disorders. Objective: The aim of this pre-planned secondary analysis was to compare the frequency and severity of symptoms associated with iron deficiency before and after (in...

Background: Extracorporeal photopheresis is a therapy based on the induction of apoptosis to cells harvested from peripheral blood, followed by direct retransfusion. Currently, there are two approaches: inline procedures, where cell harvesting, 8-methoxypsoralen (8-MOP) incubation, and UV irradiation is performed with a single device, and offline...

Chimeric antigen receptor T cells (CAR-T cells) are a novel form of cellular immunotherapy for patients with hematologic and oncologic malignancies. Known side effects of these approved cellular immunotherapies are cytokine release syndrome, immune-cell associated neurotoxicity syndrome, cytopenias, infections and long-lasting B cell aplasia. Safe...

Ex vivo generation of red blood cells (cRBCs) is an attractive tool in basic research and for replacing blood components donated by volunteers. As a prerequisite for the survival of cRBCs during storage as well as in the circulation, the quality of the membrane is of utmost importance. Besides the cytoskeleton and embedded proteins, the lipid bilay...

Red blood cell (RBC) differentiation from human induced pluripotent stem cells (hiPSCs) offers great potential for developmental studies and innovative therapies. However, ex vivo erythropoiesis from hiPSCs is currently limited by low efficiency and unphysiological conditions of common culture systems. Especially the absence of a physiological nich...

Introduction: Frequent blood donation often leads to iron deficiency and even anemia but appropriate strategies for detection and prevention are currently not mandatory. At the Medical University of Graz, we conducted a single-center prospective clinical trial to compare oral and IV iron supplementation in iron deficient blood donors including Aus...

HLA-DRB3*02:61Q , a novel HLA-DRB3 allele identified in a volunteer bone marrow donor.

Background: The ex vivo generation of human hematopoietic stem cells (HSCs) with long-term repopulating capacity and multi-lineage differentiation potential represents the holy grail of hematopoiesis research. In principle, human induced pluripotent stem cells (hiPSCs) provide the tool for both studying molecular mechanisms of hematopoietic develo...

Background: About 2-3 % of the population participates in blood donation programmes. Each whole blood donation or ten apheresis donations cause a loss of 200-250 mg of iron. As a result, one of the most common risks of regular blood donors is iron deficiency. Although this has been known for decades, in most countries, iron status is currently not...

The transcription factor c-Myb is essential for the proliferation of hematopoietic cells and has been implicated in the development of leukemia and other human cancers. Pharmacological inhibition of Myb is therefore emerging as a potential therapeutic strategy for these diseases. By using a Myb reporter cell line we have identified plumbagin and se...

A*68:02:11 differs from A*68:02:01 by a silent mutation in codon 122.

Hemolytic anemia is one of the characteristics of life-threatening extraintestinal complications in humans during infection with enterohemorrhagic Escherichia coli (EHEC). Shiga toxins (Stxs) of EHEC preferentially damage microvascular endothelial cells of the kidney and the brain, whereby occluded small blood vessels may elicit anemia through mech...

Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts con...

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts con...

Key Points Inhibition of Myb activity by a small molecule blocks proliferation of AML cells and prolongs survival of mice in an in vivo AML model.

Background: Anti-C(w) are rarely found as a source for severe fetal and neonatal hemolytic diseases. We report a case with serial intrauterine transfusions complicated by pancytopenia and cholestasis in the neonatal period. Case report: A 37-year-old woman revealed anti-C(w) with a titer of 512 in her fourth pregnancy. The fetus developed fetal...

Placental villous explant culture has been increasingly recognized as suitable model to study secretion of inflammatory and immune modulating factors by human placenta. Most of these factors likely derive from the syncytiotrophoblast, whereas extraplacental sources such as maternal peripheral blood cells are rarely considered. Due to their small si...

Chromatin modifying enzymes are frequently altered in Acute Myeloid Leukemia (AML). In the current study, we identified MYST2, a core histone acetyltransferase, to be suppressed in blast cells from AML patients compared to non-malignant hematopoietic progenitor cells. Functionally, loss of MYST2 accelerated leukemic growth and colony formation, whi...

A photochemical treatment process (PCT) utilizing amotosalen and UVA light (INTERCEPT(™) Blood System) has been developed for inactivation of viruses, bacteria, parasites and leucocytes that can contaminate blood components intended for transfusion. The objective of this study was to further characterize the safety profile of INTERCEPT-treated plat...

Background: The aim of our single-centre retrospective study presented here is to further analyse the utilisation of allogeneic blood components within a 5-year observation period (2009-2013) in trauma surgery (15,457 patients) under the measures of an educational patient blood management (PBM) initiative. Methods: After the implementation of th...

More blood components are required in cardiac surgery than in most other medical disciplines. The overall blood demand may increase as a function of the total number of cardiothoracic and vascular surgical interventions and their level of complexity, and also when considering the demographic ageing. Awareness has grown with respect to adverse event...

Epigenetic memory in induced pluripotent stem cells, with regards to their somatic cell type of origin, might lead to variations in their differentiation capacities. In this context, induced pluripotent stem cells from human CD34+ hematopoietic stem cells might be more suitable for hematopoietic differentiation than commonly used fibroblast-derived...

Zusammenfassung Die demografische Entwicklung in Europa und Deutschland lässt erwar-ten, dass der zukünftige Blutbedarf po-tenziell zunehmen wird. Dies ist zum einen dem medizinischen Fortschritt und der daraus resultierenden höheren Lebenserwartung geschuldet, zum an-deren dadurch begründet, dass ältere Patienten wegen ihrer Grunderkran-kungen und...

Nowadays patients receiving blood components are exposed to much less transfusion-transmitted infectious diseases than three decades before when among others HIV was identified as causative agent for the acquired immunodeficiency syndrome and the transmission by blood or coagulation factors became evident. Since that time the implementation of meas...

Die Versorgungslage mit Blutkomponenten und Plasmaderivaten ist in Deutschland, Österreich und der Schweiz als sehr gut zu bezeichnen. Viele gemeinsame Anstrengungen der Blutspendedienste, der pharmazeutischen Industrie und der nationalen Überwachungsbehörden haben dazu beigetragen, dass aus menschlichem Blut hergestellte „Arzneimittel“ heute sehr...

Analyses of healthy donors of G-CSF mobilized hematopoietic stem and progenitor cells (HSPC) and of patients undergoing autologous stem cell transplantation have suggested that individuals harbouring the CXCL12-A allele mobilize a higher number of CD34+ HSPC after G-CSF administration. We typed 463 healthy unrelated donors (376m/87f) who had receiv...

Several methods for isolation of MSCs from human bone marrow (BM) have been described: they are commonly isolated from the mononuclear cell fraction upon density gradient centrifugation. Alternatively, MSCs can be isolated by direct plating of BM. K. Mareschi and coworkers have compared these isolation regimens in “multipotent mesenchymal stromal s...

The origin of aberrant DNA methylation in cancer remains largely unknown. In this study, we elucidated the DNA methylome in primary Acute Promyelocytic Leukemia (APL) and the role of PML-RARα in establishing these patterns. APL patients showed increased genome-wide DNA methylation with higher variability than healthy CD34+ cells, promyelocytes and...

Massive bleeding in trauma patients is a serious challenge for all clinicians, and an interdisciplinary diagnostic and therapeutic approach is warranted within a limited time frame. Massive transfusion usually is defined as the transfusion of more than 10 units of packed red blood cells (RBCs) within 24 h or a corresponding blood loss of more than...

BACKGROUND: Demographic data illustrate clearly that people in highly developed countries get older, and the elderly need more blood transfusions than younger patients. Additionally, special extensive therapies result in an increased consumption of blood components. Beyond that the aging of the population reduces the total number of preferably youn...

Persistent Epstein-Barr virus (EBV) infection is controlled tightly by virus-specific T cells. EBV infection is reactivated intermittently over time, even in apparently healthy carriers. Changes in frequency and reactivity of memory T cells, particularly of CD8(+) origin, have not been assessed in this context. It is hypothesized that viral reactiv...

With the use of ChIP on microarray assays in primary leukemia samples, we report that acute myeloid leukemia (AML) blasts exhibit significant alterations in histone H3 acetylation (H3Ac) levels at > 1000 genomic loci compared with CD34(+) progenitor cells. Importantly, core promoter regions tended to have lower H3Ac levels in AML compared with prog...

2436 The origin of altered DNA methylation in cancer and more specifically in leukemia remains incompletely understood. One favored hypothesis suggests that aberrant methylation is recruited to direct genomic target regions of transcriptional repressor oncogenes. PML-RARα, as a transcriptional repressor oncogene, mediates a repressed chromatin stru...

The c-myb proto-oncogene encodes a transcription factor that is highly expressed in the progenitor cells of the hematopoietic system, where it regulates the expression of genes important for lineage determination, cell proliferation and differentiation. There is strong evidence that deregulation of c-myb expression is involved in the development of...

Autoimmune thrombocytopenic purpura (AITP) is an acquired autoimmune bleeding disorder, characterized by isolated thrombocytopenia because of destruction of auto-antibody-coated platelets by Fc-receptor-mediated phagocytosis. The destruction of autoantibody-sensitized platelets by FcγR-bearing phagocytic cells and the following antigen presentation...