Hartmut Radtke

Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system

Clinical trials have indicated that immunoablation followed by autologous hematopoietic stem cell transplantation (ASCT) has the potential to induce clinical remission in patients with refractory systemic lupus erythematosus (SLE), but the mechanisms have remained unclear. We now report the results of a single-center prospective study of long-term immune reconstitution after ASCT in 7 patients with SLE. The clinical remissions observed in these patients are accompanied by the depletion of autoreactive immunologic memory, reflected by the disappearance of pathogenic anti-double-stranded DNA (dsDNA) antibodies and protective antibodies in serum and a fundamental resetting of the adaptive immune system. The latter comprises recurrence of CD31(+)CD45RA(+)CD4(+) T cells (recent thymic emigrants) with a doubling in absolute numbers compared with age-matched healthy controls at the 3-year follow-up (P = .016), the regeneration of thymic-derived FoxP3(+) regulatory T cells, and normalization of peripheral T-cell receptor (TCR) repertoire usage. Likewise, responders exhibited normalization of the previously disturbed B-cell homeostasis with numeric recovery of the naive B-cell compartment within 1 year after ASCT. These data are the first to demonstrate that both depletion of the autoreactive immunologic memory and a profound resetting of the adaptive immune system are required to reestablish self-tolerance in SLE.

Daily doses of 20 mg of elemental iron compensate for iron loss in regular blood donors: a randomized, double-blind, placebo-controlled study.

BACKGROUND:  A considerable number of regular blood donors develops an iron deficiency, and the exact amount of iron required to compensate for the iron loss from whole‐blood donation in males and females is still unknown.

Rapid identification of iron deficiency in blood donors with red cell indexes provided by Advia 120

BACKGROUND:  A new generation of automated hematology analyzers allows the rapid determination of various red cell (RBC) indexes, including the percentage of hypochromic mature RBCs (HYPOm) and the hemoglobin (Hb) content of reticulocytes (CHr). These indexes have not yet been validated as measures for the detection of iron deficiency in blood donors.

Direct assessment of thymic reactivation after autologous stem cell transplantation.

Methods to quantify Th cell reconstitution after immunosuppressive therapies such as hematopoietic stem cell transplantation are becoming a key issue since persistent Th cell deficiencies may result in severe complications and adverse events. We employed here cytometric monitoring of CD31+ thymus-naive Th cells for the direct assessment of human thymic function in 10 patients undergoing autologous stem cell transplantation for severe autoimmune diseases. High frequencies of posttransplant recurring naive Th cells coexpressed CD31 and stable long-term reconstitution with elevated absolute counts of CD31+ thymus-naive Th cells that were enriched with T cell receptor excision circles was demonstrated. Cytometric monitoring of CD31+ thymus-naive Th cells enables to directly evaluate human thymic function ex vivo.

Iron supplementation and 2-unit red blood cell apheresis: a randomized, double-blind, placebo-controlled study

BACKGROUND:  The benefits of 2‐unit red blood cell (RBC) apheresis are evident, but iron depletion may be a limiting factor in using this technology. Regular iron supplementation may allow a better utilization of this technique.

Cistus incanus (CYSTUS052) for treating patients with infection of the upper respiratory tract: A prospective, randomised, placebo-controlled clinical study

In this prospective, randomized, placebo-controlled clinical study we aimed to investigate the clinical effect of a Cistus extract (CYSTUS052) in 160 patients with infections of the upper respiratory tract. The extract contains a high percentage of highly polymeric polyphenols. In cell culture and in a mouse model it exerts antiviral and antimicrobial activities. Principal active constituents of the genus Cistus are polyphenolic compounds. Plant-derived polyphenols have been shown to be strong antioxidants with potential health benefits. Various reports have appeared on the antiviral and antibacterial potential, including several reports describing the antiviral activity of polyphenols against influenza virus. Clinical studies on the effectiveness of Cistus incanus are scarce. Only one controlled application observation study demonstrated the effectiveness of a Cistus extract. The present randomised, placebo-controlled clinical study was designed to compare the symptom scores in patients with common cold treated either with CYSTUS052 or with placebo. A score of subjective symptoms decreased significantly over the course of treatment with Cistus, whereas treatment with placebo resulted in a less distinct decrease of symptoms. Among the inflammatory markers investigated, the C-reactive protein was mostly affected by Cistus and decreased significantly in the treatment group.

Effect of CYSTUS052® and green tea on subjective symptoms in patients with infection of the upper respiratory tract

Examples of medicinal herbs that have been perpetuated along several generations based simply on a folk tradition are Cistus and green tea. The principal active constituents of the genus Cistus and green tea are polyphenolic compounds. Polyphenols exhibit a wide range of antibacterial, antifungal and antiinflammatory effects.

Influence of 30 Gy Gamma Irradiation on the Quality of Red Blood Cell Concentrates in Several Storage Media

Background: The transfusion-associated graft versus host disease (t-GvHD) occurring in immunosuppressed patients can be prevented by irradiation of red blood cell concentrates (RCCs) with gamma irradiation at a dose of 30 Gy prior to transfusion. The aim of this study was to investigate, whether the irradiation of leukocyte-depleted RCCs in different storage media (SAG-M, PAGGS-M, or Adsol) may cause deterioration of red blood cells (RBC), resulting in a shortened shelf life of the RCC. Material and Methods:According to manufacturing (manually, apheresis), storage medium used (SAG-M, PAGGS-M, Adsol) and processing of leukocyte depletion (filtered, nonfiltered), 192 RCCs were separated into 8 groups with 24 RCCs each. Each group was divided into two subgroups. One was irradiated (30 Gy), the other one was used as control. Until the end of shelf life, pH, the concentrations of Na+ , K+ , lactate, glucose, 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP), parameters of blood cell count, and external hemoglobin were measured every week. Results:The metabolic parameters did not show significant differences between nonirradiated and irradiated RCCs. K+ efflux and hemolysis were significantly higher in the irradiated RCCs after the first week of storage. The values of hemolysis remained below the recommended limit of 0.8% of the hemoglobin content of RCCs until the 28th day of storage. After 28 days of storage the mean values of K+ increased by 25% compared to the control samples at the end of shelf life. The mean corpuscular volume (MCV) was significantly higher in the irradiated RCCs with significant differences between the various storage media. Leukocyte-depleted RCCs showed partly smaller rates of hemolysis than unfiltered RCCs. Conclusions:The determined in vitro parameters of irradiated and leukocyte-depleted RCCs stored in SAG-M, PAGGS-M or Adsol revealed no significant quantitative changes until 28th day of storage compared to those of nonirradiated RCCs.

Compensating for iron loss in regular blood donors using ferrous gluconate and ascorbic acid

regarding the number of potentially inappropriate transfusions of fresh frozen plasma (FFP) in the United States. Like most institutions, we constantly strive to minimize the number of inappropriate FFP transfusions. We find, however, that the blood bank staff flags 25 to 30 percent of transfused FFP units as not meeting transfusion guidelines. Other institutions have reported similar percentages of inappropriate FFP transfusions. 2 Although the significance of a minimally elevated prothrombin time (PT)-international normalized ratio (INR) has not been definitively proven, 3 many clinicians will prophylactically order FFP for a patient with a minimally elevated PT-INR. Although guidelines published by the AABB and others define appropriateness of FFP administration based on PT (or partial thromboplastin time) greater than 1.5 times normal, we find that defining the transfusion guidelines in terms of INR makes it easier for our clinicians to quickly evaluate the coagulation status of patients. Our guidelines suggest that FFP be considered only when the patient’s INR is equal to or greater than 1.6. We use thromboplastin with an international sensitivity index of 1.01 in our PT assay and so the reported INR is essentially the ratio of the patient’s PT to the normal value. At a glance, the clinicians can gain the same information from the INR that they would obtain by performing a calculation on the PT. Furthermore, because the PT reference range for each new batch of reagents may change slightly, we avoid the potential problem of clinicians applying a previously calculated PT transfusion cutoff to a new reference range. During an audit of monthly FFP utilization, we identified 22 nontrauma patients, receiving a total of 68 units of apheresis FFP (500 mL), who did not meet criteria for receipt of FFP. Some patients received FFP on more than one occasion. All received appropriate dosages of FFP, at least 10 mL per kg, with a mean of 1.9 units of FFP per transfusion (range, 1 to 6 units). The INR values around the time of the transfusion were recorded with pretransfusion INRs available at a median time of 6.3 hours before transfusion (range, 0.7-21 hr) and posttransfusion INRs available at a median of 3.9 hours after initiation of transfusion (range, 0.5-21 hr). The mean pretransfusion INR was 1.37 (range, 1.1-1.6), and the mean change was a decrease of 0.03 INR per unit of FFP infused. The changes in INR from transfusion of these 68 units and 10 control patients receiving FFP transfusions that did meet criteria are summarized in Fig. 1. We also calculated INRs for 20 units of apheresis FFP (500 mL). The mean INR of these FFP units was 1.1 (range, 0.9-1.3) (Fig. 2). These values are in agreement with those presented in other studies. 4,5

Durchführung präparativer Hämapheresen zur Gewinnung von Blutbestandteilkonzentraten – Empfehlungen zur präparativen Hämapherese der Deutschen Gesellschaft für Transfusionsmedizin und Immunhämatologie (DGTI)*

a Institut fur Transfusionsmedizin, Universitatsklinikum Leipzig, b Institut fur Transfusionsmedizin, Universitatsklinikum Essen, c Institut fur Transfusionsmedizin, Charite – Universitatsmedizin Berlin, Campus Mitte, Berlin d Institut fur Klinische Transfusionsmedizin und Immungenetik Ulm gGmbH, eTransfusionsmedizinische und Hamostaseologische Abteilung, Universitatsklinikum Erlangen, Deutschland