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Article ; Online: Efficacy and tolerability of old and new drugs used in the treatment of immune thrombocytopenia

Fabian Depré / Nasra Aboud / Beate Mayer / Abdulgabar Salama

PLoS ONE, Vol 13, Iss 6, p e

Results from a long-term observation in clinical practice.

2018 Volume 0198184

Abstract: BACKGROUND:Many patients with immune thrombocytopenia (ITP) may require special attention and long-term treatment. Little is known on the efficacy and tolerability of the drugs used in practice. MATERIAL AND METHODS:We retrospectively reviewed the ... ...

Abstract	BACKGROUND:Many patients with immune thrombocytopenia (ITP) may require special attention and long-term treatment. Little is known on the efficacy and tolerability of the drugs used in practice. MATERIAL AND METHODS:We retrospectively reviewed the results of therapy of 400 patients with chronic ITP. All Patients were treated at our institution between 1996-2016 under consideration of guidelines, general recommendations, and individual aspects, including gender, age, weight, comorbidity, patient's medical history and bleeding risk. RESULTS:Treatment was not required in 25% of patients (n = 100) during observation. In treated patients (n = 300), the rate of patients that responded and tolerated treatment with prednisolone was 59% (52/88), with azathioprine 32% (29/90), with eltrombopag 49% (31/63), with romiplostim 59% 27/45, with IVIG (intravenous immunoglobulines) 75% (94/126), with anti-D 37% (19/52) and with dexamethasone 60% (25/42) patients. Eighteen treated patients (6%) entered sustained remission after treatment with various drugs. Twenty-six patients underwent splenectomy (Splx) resulting in sustained remission in 15 cases (60%). Only two patients remained refractory to Splx and to all used drugs. DISCUSSION:None of the currently available drugs used in the treatment of ITP are invariably safe and effective. Responses, the duration of response, intolerability, and the course of disease are unpredictable. Although the treatment of ITP has considerably improved in the recent years, the currently available drugs may rarely cure affected patients. The need for safe and effective therapy in ITP is evident. Optimal treatment decisions for each patient remains a challenge in many cases.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Oxidative Stress Is Predominant in Female but Not in Male Patients with Autoimmune Thrombocytopenia

Julian Kamhieh-Milz / Abdulgabar Salama

Oxidative Medicine and Cellular Longevity, Vol

2014 Volume 2014

Keywords	Cytology ; QH573-671 ; Biology (General) ; QH301-705.5 ; Science ; Q ; DOAJ:Cytology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Safety and Efficacy of Romiplostim in Patients with Severe, Chronic Idiopathic Thrombocytopenic Purpura

Oliver Meyer / Abdulgabar Salama

Clinical Medicine Insights: Therapeutics, Vol 2012, Iss 4, Pp 75-

2012 Volume 83

Keywords	Therapeutics. Pharmacology ; RM1-950 ; Medicine ; R ; DOAJ:Therapeutics ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	English
Publishing date	2012-04-01T00:00:00Z
Publisher	Libertas Academica
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Identification of novel autoantigens via mass spectroscopy-based antibody-mediated identification of autoantigens (MS-AMIDA) using immune thrombocytopenic purpura (ITP) as a model disease

Kamhieh-Milz, Julian / Abdulgabar Salama / Hatice Celik / Omid Khorramshahi / Reham Fadl Hassan Moftah / Viktor Sterzer

Journal of proteomics. 2017 Mar. 22, v. 157

2017

Abstract: Immune thrombocytopenic purpura (ITP) is one of the best characterized autoimmune diseases. Autoantibodies (AABs) against platelet antigens are considered as the diagnostic hallmark of ITP, but are detectable in only 50% of patients. We designed and ... ...

Abstract	Immune thrombocytopenic purpura (ITP) is one of the best characterized autoimmune diseases. Autoantibodies (AABs) against platelet antigens are considered as the diagnostic hallmark of ITP, but are detectable in only 50% of patients. We designed and applied a novel proteomic approach termed Mass Spectroscopy-based Antibody-Mediated Identification of Autoantigens (MS-AMIDA) for platelet antigens. Patients were separated into patients with classical AABs [ITP(+)] and patients without AABs [ITP(−)]. Altogether, 181 potential AAGs were found in ITP(+) and 135 AAGs in ITP(−), with 34 and 23 AAGs reproducibly found in two runs of MS-AMIDA. After subtracting identifiers from the controls, 57 AAGs in ITP(+) and 29 AAGs in ITP(+) remained, with 16 AAGs commonly found in ITP(+) and ITP(−) patients. Label-free quantification (LFQ) revealed 15 potential AAGs that are quantitatively stronger in ITP. Dot blot validation was performed on hexokinase 1 (HK1), E1 pyruvate dehydrogenase (E1-PDH), coagulation factor XIII, filamin A (FLNA), non-muscle myosin 9. Eleven patients were found to have anti-HK1 AABs, one patient had anti-E1-PDH AABs, and two patients had anti-FLNA AABs. Most antigens were of intracellular origin with significant association with actin-cytoskeleton and regulation of programmed cell death. In conclusion, novel AAGs for ITP were identified using MS-AMIDA.
Keywords	apoptosis ; autoantibodies ; autoantigens ; autoimmune diseases ; coagulation ; filamin ; hexokinase ; myosin ; patients ; pyruvate dehydrogenase (lipoamide) ; thrombocytopenic purpura
Language	English
Dates of publication	2017-0322
Size	p. 59-70.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2400835-7
ISSN	1876-7737 ; 1874-3919
ISSN (online)	1876-7737
ISSN	1874-3919
DOI	10.1016/j.jprot.2017.01.012
Database	NAL-Catalogue (AGRICOLA)

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Article: Secretome profiling of apheresis platelet supernatants during routine storage via antibody-based microarray

Kamhieh-Milz, Julian / Abdulgabar Salama / Hatice Celik / Jörg D. Hoheisel / Kamran Movassaghi / Mohamed S.S. Alhamdani / Omid Khorramshahi / Sahime Keski / Shakhawan A. Mustafa / Viktor Sterzer

Journal of proteomics. 2017 Jan. 06, v. 150

2017

Abstract: Platelet storage lesions (PSLs) occur during platelet concentrate (PC) storage. Adverse transfusion reactions (ATRs) have been demonstrated to be more frequent in older PCs and removal of the supernatant prior to transfusion reduces their occurrence. ... ...

Abstract	Platelet storage lesions (PSLs) occur during platelet concentrate (PC) storage. Adverse transfusion reactions (ATRs) have been demonstrated to be more frequent in older PCs and removal of the supernatant prior to transfusion reduces their occurrence. Proteomic profiling of PC supernatants was thus performed to identify proteins associated with PSLs and ATRs. Twenty-four PCs were investigated daily from day 0 to day 9 for platelet pre-activation (PPA), platelet-derived extracellular vesicles (PEVs), and platelet function. Using antibody microarrays, 673 extracellular proteins were analysed in PC supernatants on days 0, 3, 5, 7, and 9. During 5days of storage, PPA and PEVs continuously increased (P<0.0001). Platelet function was observed to remain stable within the first 5days (P=0.1751) and decreased thereafter. Comparison of all time points to day 0 revealed the identification of 136 proteins that were significantly changed in abundance during storage, of which 72 were expressed by platelets. Network analysis identified these proteins to be predominantly associated with exosomes (P=4.61×10−8, n=45 genes) and two clusters with distinct functions were found with one being associated with haemostasis and the other with RNA binding. These findings may provide an explanation for ATRs.Changes in platelet concentrate (PC) supernatants during storage have been so far only poorly addressed and high abundant proteins burden the identification of quantitative changes in the secretome. We applied a high-throughput antibody microarray allowing for the sensitive quantification of 673 extracellular factors. PCs account for the highest number of adverse transfusion reactions (ATRs). ATRs have been demonstrated to be more frequent in older PCs and removal of the supernatant prior to transfusion reduces their occurrence. Comprehensive interpretation of the changing proteins in the secretome during platelet storage under blood banking conditions may help to identify mechanisms leading to the occurrence of adverse transfusion reactions.
Keywords	antibody microarrays ; blood platelets ; exosomes ; genes ; hemostasis ; microarray technology ; proteins ; proteomics ; RNA
Language	English
Dates of publication	2017-0106
Size	p. 74-85.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2400835-7
ISSN	1876-7737 ; 1874-3919
ISSN (online)	1876-7737
ISSN	1874-3919
DOI	10.1016/j.jprot.2016.07.028
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Transcriptional Profiling of the Hematopoietic Support of Interleukin-Stimulated Human Umbilical Vein Endothelial Cells (HUVECs)

Gürkan Bal / Julian Kamhieh-Milz / Matthias Futschik / Thomas Häupl / Abdulgabar Salama / Anja Moldenhauer

Cell Transplantation, Vol

2012 Volume 21

Abstract: Endothelial cells can be successfully used to maintain or increase the number of hematopoietic stem cells in vitro. Previously we identified hematopoietic progenitor cell (HPC) expansion or survival benefit induced by IL-1β-, IL-3-, and IL-6-stimulated ... ...

Abstract	Endothelial cells can be successfully used to maintain or increase the number of hematopoietic stem cells in vitro. Previously we identified hematopoietic progenitor cell (HPC) expansion or survival benefit induced by IL-1β-, IL-3-, and IL-6-stimulated human umbilical vein endothelial cell (HUVEC) supernatants. In order to identify molecular mechanisms that support hematopoiesis, we examined the time-dependent expression profiles of IL-1β-, IL-3-, and IL-6-stimulated HUVECs via microarray. Here, we present 24 common upregulated elements and three common downregulated elements of IL-1β- and IL-3-stimulated HUVECs, with these factors exhibiting great potential for the observed HPC expansion. Furthermore, metabolic pathway analysis resulted in the identification of nonproteinogenic factors such as prostaglandin E 2 (PGE 2 ) and nitric oxide (NO) and determined their HPC expansion potential via delta, methylcellulose, and cobblestone assays. We confirmed PGE 2 and spermine as hematopoietic expansion factors. Furthermore, we identified several factors such as SSAT, extracellular matrix components, microRNA21, and a microvesicle-mediated cross-talk between the endothelium and HPCs that may play a crucial role in determining stem cell fate. Our results suggest that microarray in combination with functional annotations is a convenient method to identify novel factors with great impact on HPC proliferation and differentiation.
Keywords	Medicine ; R
Subject code	570
Language	English
Publishing date	2012-02-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Advances in ITP--therapy and quality of life--a patient survey.

Axel C Matzdorff / Gabriele Arnold / Abdulgabar Salama / Helmut Ostermann / Sonja Eberle / Simone Hummler

PLoS ONE, Vol 6, Iss 11, p e

2011 Volume 27350

Abstract: BACKGROUND: Current guidelines recommend glucocorticoids and splenectomy as standard 1(st) and 2(nd) line treatments for chronic immune thrombocytopenia (ITP). We sought to find out how German ITP-patients are treated with respect to these guidelines. ... ...

Abstract	BACKGROUND: Current guidelines recommend glucocorticoids and splenectomy as standard 1(st) and 2(nd) line treatments for chronic immune thrombocytopenia (ITP). We sought to find out how German ITP-patients are treated with respect to these guidelines. METHODS: Members of a patient support association ≥18 years with a self-reported history of chronic ITP>12 months were surveyed with a web-based questionnaire. RESULTS: 122 questionnaires were evaluated. 70% of patients had chronic ITP for more than 5 years and 20% an average platelet count of ≤30·10(9)/L. 41% of the patients reported haematomas or petechiae more than once or twice and up to 12 times or more per year and 17% oropharyngeal and nasal bleeds. 11% had been admitted to hospital during the last 12 months. 88% had received or currently receive glucocorticoids, 27% were splenectomised. IVIG had been given to 55%, rituximab to 22%, anti-D to 12%, ciclosporin to 7%, while complementary and alternative medical treatments had been used by 36%. 50 women responded to questions concerning pregnancy. 14 (28%) had been advised not to become pregnant. 23 reported pregnancies and 10 (44%) required treatment for their ITP during pregnancy. CONCLUSION: Glucocorticoids are the most common therapy for chronic ITP but complementary and alternative treatments already come second and less than ⅓ of patients are splenectomised. This and the frequent use of complementary medicines suggests patients' dissatisfaction with conventional approaches. Many patients receive off-label therapies. There is a major need for adequate counselling and care for pregnant ITP-patients.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hemolysis after Oral Artemisinin Combination Therapy for Uncomplicated Plasmodium falciparum Malaria

Florian Kurth / Tilman Lingscheid / Florian Steiner / Miriam S. Stegemann / Sabine Bélard / Nikolai Menner / Peter Pongratz / Johanna Kim / Horst von Bernuth / Beate Mayer / Georg Damm / Daniel Seehofer / Abdulgabar Salama / Norbert Suttorp / Thomas Zoller

Emerging Infectious Diseases, Vol 22, Iss 8, Pp 1381-

2016 Volume 1386

Abstract: Episodes of delayed hemolysis 2–6 weeks after treatment of severe malaria with intravenous artesunate have been described. We performed a prospective observational study of patients with uncomplicated malaria to investigate whether posttreatment ... ...

Abstract	Episodes of delayed hemolysis 2–6 weeks after treatment of severe malaria with intravenous artesunate have been described. We performed a prospective observational study of patients with uncomplicated malaria to investigate whether posttreatment hemolysis also occurs after oral artemisinin-based combination therapy. Eight of 20 patients with uncomplicated malaria who were given oral artemisinin-based combination therapy met the definition of posttreatment hemolysis (low haptoglobin level and increased lactate dehydrogenase level on day 14). Five patients had hemolysis persisting for 1 month. Patients with posttreatment hemolysis had a median decrease in hemoglobin level of 1.3 g/dL (interquartile range 0.3–2.0 g/dL) in the posttreatment period, and patients without posttreatment hemolysis had a median increase of 0.3 g/dL (IQR −0.1 to 0.7 g/dL; p = 0.002). These findings indicate a need for increased vigilance for hemolytic events in malaria patients, particularly those with predisposing factors for anemia.
Keywords	malaria ; uncomplicated malaria ; Plasmodium falciparum ; parasites ; hemolysis ; artemisinin ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2016-08-01T00:00:00Z
Publisher	Centers for Disease Control and Prevention
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Differentially Expressed MicroRNAs in Maternal Plasma for the Noninvasive Prenatal Diagnosis of Down Syndrome (Trisomy 21)

Julian Kamhieh-Milz / Reham Fadl Hassan Moftah / Gürkan Bal / Matthias Futschik / Viktor Sterzer / Omid Khorramshahi / Martin Burow / Gundula Thiel / Annegret Stuke-Sontheimer / Rabih Chaoui / Sundrela Kamhieh-Milz / Abdulgabar Salama

BioMed Research International, Vol

2014 Volume 2014

Abstract: Objectives. Most developmental processes are under the control of small regulatory RNAs called microRNAs (miRNAs). We hypothesize that different fetal developmental processes might be reflected by extracellular miRNAs in maternal plasma and may be ... ...

Abstract	Objectives. Most developmental processes are under the control of small regulatory RNAs called microRNAs (miRNAs). We hypothesize that different fetal developmental processes might be reflected by extracellular miRNAs in maternal plasma and may be utilized as biomarkers for the noninvasive prenatal diagnosis of chromosomal aneuploidies. In this proof-of-concept study, we report on the identification of extracellular miRNAs in maternal plasma of Down syndrome (DS) pregnancies. Methods. Using high-throughput quantitative PCR (HT-qPCR), 1043 miRNAs were investigated in maternal plasma via comparison of seven DS pregnancies with age and fetal sex matched controls. Results. Six hundred and ninety-five miRNAs were identified. Thirty-six significantly differentially expressed mature miRNAs were identified as potential biomarkers. Hierarchical cluster analysis of these miRNAs resulted in the clear discrimination of DS from euploid pregnancies. Gene targets of the differentially expressed miRNAs were enriched in signaling pathways such as mucin type-O-glycans, ECM-receptor interactions, TGF-beta, and endocytosis, which have been previously associated with DS. Conclusions. miRNAs are promising and stable biomarkers for a broad range of diseases and may allow a reliable, cost-efficient diagnostic tool for the noninvasive prenatal diagnosis of DS.
Keywords	Medicine ; R
Subject code	500 ; 610
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Proteomic Profiling of Secreted Proteins for the Hematopoietic Support of Interleukin-Stimulated Human Umbilical Vein Endothelial Cells

Gürkan Bal / Julian Kamhieh-Milz / Viktor Sterzer / Muhammad Al-Samman / Janusz Debski / Oliver Klein / Sundrela Kamhieh-Milz / Sucharit Bhakdi / Abdulgabar Salama

Cell Transplantation, Vol

2013 Volume 22

Abstract: Human umbilical cord vein endothelial cells (HUVECs) secrete a number of factors that greatly impact the proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs). These factors remain largely unknown. Here, we report on the ... ...

Abstract	Human umbilical cord vein endothelial cells (HUVECs) secrete a number of factors that greatly impact the proliferation and differentiation of hematopoietic stem and progenitor cells (HSPCs). These factors remain largely unknown. Here, we report on the most comprehensive proteomic profiling of the HUVEC secretome and identified 827 different secreted proteins. Two hundred and thirty-one proteins were found in all conditions, whereas 369 proteins were identified only under proinflammatory conditions following IL-1β, IL-3, and IL-6 stimulation. Thirteen proteins including complement factor b (CFb) were identified only under IL-1β and IL-3 conditions and may potentially represent HSPC proliferation factors. The combination of bioinformatics and gene ontology annotations indicates the role of the complement system and its activation. Furthermore, CFb was found to be transcriptionally strongly upregulated. Addition of complement component 5b-9 (C5b-9) monoclonal antibody to the stem cell expansion assay was capable of significantly reducing their proliferation. This study suggests a complement-mediated cross-talk between endothelial cells and HSPCs under proinflammatory conditions.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2013-07-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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