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ABSTRACT: This study aims to determine prevalence and incidence of anemia in the general population in Germany and evaluate a potential role of serum-free light chains (FLC) as biomarker in anemia. The population-based Heinz Nixdorf Recall Study comprises 4,814 men and women aged 45-75 years. Hemoglobin <13 g/dl in men and <12 g/dl in women defined anemia. Laboratory data was used to classify cases into renal, iron deficiency (IDA), vitamin B(12)/folic acid deficiency, anemia of chronic disease (ACD), and unexplained anemia (UA). Follow-up data was available from annual questionnaires, death certificates, and 5-year follow-up visit (5-year FU). Anemia cases (152) were identified (prevalence 3.2 %, 95 % CI 2.7-3.7). In participants aged 65 or older, prevalence was 4.3 % (95 % CI 2.9-6.0) in both men and women. Main anemia subtypes were: IDA 19 %, ACD 25 %, and UA 44 %. Incidence increased with age and was 12.8/1,000 person-years and 10.9/1,000 person-years in men and women aged 65 or older, respectively. UA was characterized by elevated FLC. Participants with elevated FLC and high-sensitivity C-reactive protein (hsCRP) had an increased risk of anemia at 5-year FU. FLC-alone or in combination with hsCRP-may serve as biomarker indicating an increased risk of developing anemia.
Annals of Hematology 02/2013; · 2.62 Impact Factor
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ABSTRACT: The cellular origin of chronic lymphocytic leukemia (CLL) is still debated, although this information is critical to understanding
its pathogenesis. Transcriptome analyses of CLL and the main normal B cell subsets from human blood and spleen revealed that
immunoglobulin variable region (IgV) gene unmutated CLL derives from unmutated mature CD5+ B cells and mutated CLL derives from a distinct, previously unrecognized CD5+CD27+ post–germinal center B cell subset. Stereotyped V gene rearrangements are enriched among CD5+ B cells, providing independent evidence for a CD5+ B cell derivation of CLL. Notably, these CD5+ B cell populations include oligoclonal expansions already found in young healthy adults, putatively representing an early
phase in CLL development before the CLL precursor lesion monoclonal B cell lymphocytosis. Finally, we identified deregulated
proteins, including EBF1 and KLF transcription factors, that were not detected in previous comparisons of CLL and conventional
B cells.
Journal of Experimental Medicine 11/2012; 209(12):2183-2198. · 13.85 Impact Factor
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ABSTRACT: The distinction of CLL from other mature B-cell neoplasms, especially from leukemic forms of mantle cell lymphoma or splenic marginal zone lymphoma, can be difficult but has important prognostic and therapeutic implications. We measured CLLU1 (CLL upregulated gene1) mRNA by qPCR and found a highly significant difference between CLL and other lymphoid neoplasms (AUC 0.96, 95%CI 0.93-0.99). Based on our cut-off values we can predict CLL and other mature B-cell neoplasms with high probability (PPV 99% and 94%). Analysis of CLLU1 expression is a rapid and reliable tool that may facilitate the diagnosis of mature B-cell neoplasms especially in inconclusive cases.
Leukemia research 06/2012; 36(9):1204-7. · 2.36 Impact Factor
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Ludger Sellmann,
Alexander Carpinteiro,
Holger Nückel,
René Scholtysik,
Dörte Siemer,
Ludger Klein-Hipass,
Dieter Kube, Jan Dürig,
Ulrich Dührsen,
Jens Stanelle,
Ralf Küppers
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ABSTRACT: Alterations in the function of the p53 pathway are frequently described in chronic lymphocytic leukemia (CLL), mostly associated with deletion of 17p13 and/or mutations of the TP53 gene. In the present study, we investigated 103 CLLs for the impact of protein expression of full-length p53 and its isoforms β and γ. A strong correlation between deletions of 17p13 and an accumulation of full-length p53 protein was found and was associated with a worse outcome compared to CLL with normal p53 (treatment-free survival p < 0.001, overall survival p = 0.04). Interestingly, the relative expression levels between full-length p53 protein and its isoforms β and γ were significantly altered in CLL even without deletions of 17p13, compared to normal B-cells (p = 0.005). Furthermore, CLLs with higher p53 protein ratios showed worse clinical courses compared to CLLs with lower p53 protein ratios. Taken together, the differential expression of p53 isoforms could disrupt the p53 response and contribute to CLL pathogenesis.
Leukemia & lymphoma 02/2012; 53(7):1282-8. · 2.40 Impact Factor
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ABSTRACT: Disruption of circadian rhythm is believed to play a critical role in cancer development. Cryptochrome 1 (CRY1) is a core component of the mammalian circadian clock and we have previously shown its deregulated expression in a subgroup of patients with chronic lymphocytic leukemia (CLL). Using real-time RT-PCR in a cohort of 76 CLL patients and 35 normal blood donors we now demonstrate that differential CRY1 mRNA expression in high-risk (HR) CD38+/immunoglobulin variable heavy chain gene (IgVH) unmutated patients as compared to low-risk (LR) CD38-/IgVH mutated patients can be attributed to down-modulation of CRY1 in LR CLL cases. Analysis of the DNA methylation profile of the CRY1 promoter in a subgroup of 57 patients revealed that CRY1 expression in LR CLL cells is silenced by aberrant promoter CpG island hypermethylation. The methylation pattern of the CRY1 promoter proved to have high prognostic impact in CLL where aberrant promoter methylation predicted a favourable outcome. CRY1 mRNA transcript levels did not change over time in the majority of patients where sequential samples were available for analysis. We also compared the CRY1 expression in CLL with other lymphoid malignancies and observed epigenetic silencing of CRY1 in a patient with B cell acute lymphoblastic leukemia (B-ALL).
PLoS ONE 01/2012; 7(3):e34347. · 4.09 Impact Factor
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ABSTRACT: We determined the prevalence and progression rate of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS (LCMGUS) in Germany utilizing the biobank of the population-based Heinz Nixdorf Recall Study. The Heinz Nixdorf Recall Study comprises 4,814 men and women aged 45-75 years. To detect monoclonal proteins, standard serum electrophoresis was combined with parallel screening immunofixation using pentavalent antisera. Additionally, free light chains (FLC) were measured in all samples. Definition of MGUS included M-protein concentration, laboratory results, and disease history. LCMGUS was defined as abnormal FLC ratio, increase in FLC causing the abnormal ratio, and lack of intact immunoglobulin. One hundred sixty-five MGUS cases were identified among 4,702 screened samples (prevalence 3.5%, 95% confidence interval (CI) 3.0-4.1; median age 63 years, range 47-75 years; 103 (62%) male; IgG 59%, IgA 17%, IgM 17%, biclonal 4.8%, kappa 56%, and lambda 44%). Five cases progressed (0.6%/year, 95% CI 0.2-1.4). An abnormal FLC ratio was detected in 220 samples. Thirty-nine of these showed intact immunoglobulin. Thirty-four of the remaining met LCMGUS criteria (prevalence 0.7%, 95% CI 0.5-1.0). None of the LCMGUS cases progressed. We demonstrate a MGUS prevalence of 3.5% and a LCMGUS prevalence of 0.7% in the general population aged 45-75 years in Germany using a sensitive screening approach.
Annals of Hematology 07/2011; 91(2):243-8. · 2.62 Impact Factor
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Semra Aydin,
Florian Grabellus,
Lewin Eisele,
Michael Möllmann,
Maher Hanoun,
Peter Ebeling,
Thomas Moritz,
Alexander Carpinteiro,
Holger Nückel,
Ali Sak,
Joachim R Göthert,
Ulrich Dührsen, Jan Dürig
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ABSTRACT: We explored the role of CD38 and functionally associated molecular risk factors in a recently described chronic lymphocytic leukemia (CLL) nonobese diabetic/ severe combined immunodeficient xenograft model. Intravenous injection of peripheral blood mononuclear cells from 73 patients with CLL into 244 mice resulted in robust engraftment of leukemic cells into the murine spleens detected 4 wks after transplantation. Leukemic cell engraftment correlated significantly (P < 0.05) with markers reflecting disease activity, e.g., Binet stage and lymphocyte doubling time, and the expression of molecular risk factors including CD38, CD49d, ZAP-70, and IgVH mutational status. Increased engraftment levels of CD38+ as compared to CD38- CLL cells could be attributed, in part, to leukemic cell proliferation as evidenced by combined immunostaining of murine spleen sections for Ki-67 and CD20. In short-term (24 h) homing assays, CD38+ CLL cells migrated more efficiently to the bone marrow of the recipient animals than their CD38- counterparts. Finally, CD38 expression by the leukemic cells was found to be dynamic in that it was regulated not only by elements of the murine microenvironment but also by co-engrafting non-malignant human T cells. This model could be useful for evaluating the biological basis of CLL growth in the context of the hematopoietic microenvironment as well as preclinical testing of novel compounds.
European Journal Of Haematology 07/2011; 87(1):10-9. · 2.61 Impact Factor
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William G Wierda,
Thomas J Kipps, Jan Dürig,
Laimonas Griskevicius,
Stephan Stilgenbauer,
Jirí Mayer,
Lukás Smolej,
Georg Hess,
Rasa Griniute,
Francisco J Hernandez-Ilizaliturri,
Swaminathan Padmanabhan,
Michele Gorczyca,
Chai-Ni Chang,
Geoffrey Chan,
Ira Gupta,
Tina G Nielsen,
Charlotte A Russell
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ABSTRACT: We conducted an international phase 2 trial to evaluate 2 dose levels of ofatumumab, a human CD20 mAb, combined with fludarabine and cyclophosphamide (O-FC) as frontline therapy for chronic lymphocytic leukemia (CLL). Patients with active CLL were randomized to ofatumumab 500 mg (n = 31) or 1000 mg (n = 30) day 1, with fludarabine 25 mg/m(2) and cyclophosphamide 250 mg/m(2) days 2-4, course 1; days 1-3, courses 2-6; every 4 weeks for 6 courses. The first ofatumumab dose was 300 mg for both cohorts. The median age was 56 years; 13% of patients had a 17p deletion; 64% had β2-microglobulin > 3.5 mg/L. Based on the 1996 National Cancer Institute Working Group (NCI-WG) guidelines, the complete response (CR) rate as assessed by an independent review committee was 32% for the 500-mg and 50% for the 1000-mg cohort; the overall response (OR) rate was 77% and 73%, respectively. Based on univariable regression analyses, β2-microglobulin and the number of O-FC courses were significantly correlated (P < .05) with CR and OR rates and progression-free survival (PFS). The most frequent Common Terminology Criteria (CTC) grade 3-4 investigator-reported adverse events were neutropenia (48%), thrombocytopenia (15%), anemia (13%), and infection (8%). O-FC is active and safe in treatment-naive patients with CLL, including high-risk patients. This trial was registered at www.clinicaltrials.gov as NCT00410163.
Blood 06/2011; 117(24):6450-8. · 9.90 Impact Factor
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Ludger Sellmann,
Dirk de Beer,
Marius Bartels,
Bertram Opalka,
Holger Nückel,
Ulrich Dührsen, Jan Dürig,
Marc Seifert,
Dörte Siemer,
Ralf Küppers,
Gabriela M Baerlocher,
Alexander Röth
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ABSTRACT: In the present study, telomere length, telomerase activity, the mutation load of immunoglobulin variable heavy chain (IGHV) genes, and established prognostic factors were investigated in 78 patients with chronic lymphocytic leukaemia (CLL) to determine the impact of telomere biology on the pathogenesis of CLL. Telomere length was measured by an automated multi-colour flow-FISH, and an age-independent delta telomere length (ΔTL) was calculated. CLL with unmutated IGHV genes was associated with shorter telomeres (p = 0.002). Furthermore, we observed a linear correlation between the frequency of IGHV gene mutations and elongation of telomeres (r = 0.509, p < 0.001). With respect to prognosis, a threshold ΔTL of -4.2 kb was the best predictor for progression-free and overall survival. ΔTL was not significantly altered over time or with therapy. The correlation between the mutational load in IGHV genes and the ΔTL in CLL might reflect the initial telomere length of the putative cell of origin (pre- versus post-germinal center B cells). In conclusion, the ΔTL is a reliable prognostic marker for patients with CLL. Short telomeres and high telomerase activity as occurs in some patients with CLL with a worse prognosis might be an ideal target for treatment with telomerase inhibitors.
International journal of hematology 01/2011; 93(1):74-82. · 1.17 Impact Factor
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Ludger Sellmann,
Rene Scholtysik,
Markus Kreuz,
Sandra Cyrull,
Enrico Tiacci,
Jens Stanelle,
Alexander Carpinteiro,
Holger Nückel,
Tanja Boes,
Stefan Gesk,
Reiner Siebert,
Ludger Klein-Hitpass,
Ulrich Dührsen, Jan Dürig,
Ralf Küppers
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ABSTRACT: To understand the influence of chromosomal alterations on gene expression in a genome-wide view, chromosomal imbalances detected by single nucleotide polymorphism (SNP) chips were compared with global gene expression in 16 cases of chronic lymphocytic leukemia (CLL). A strong concordance between chromosomal gain or loss and increased or reduced expression of genes in the affected regions was found, respectively. Regions of uniparental disomy (UPD) were rare and had usually no consistent influence on gene expression, but in one instance, a large UPD was associated with a downregulation of most genes in the affected chromosome. The frequently deleted miRNAs, MIRN15A and MIRN16-1, did not show a reduced expression in cases with monoallelic deletions. The BCL2 protein, considered to be downregulated by these miRNAs, was upregulated not only in CLL with biallelic deletion of MIRN15A and MIRN16-1, but also in cases with monoallelic deletion. This suggests a complex regulation of BCL2 levels in CLL cells. Taken together, in CLL, a global gene dosage effect exists for chromosomal gains and deletions and in some instances for UPDs. We did not confirm a consistent correlation between MIRN15A and MIRN16-1 expression levels and BCL2 protein levels, indicating a complex regulation of BCL2 expression.
Cancer genetics and cytogenetics 12/2010; 203(2):149-60. · 1.54 Impact Factor
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Journal of Clinical Oncology 10/2010; 28(30):e613; author reply e614. · 18.37 Impact Factor
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ABSTRACT: This study assessed the feasibility and safety of out of hospital management of acute myeloid leukemia (AML) patients during consolidation therapy.
103 consolidation cycles were analyzed retrospectively. All patients received treatment as inpatients; they were discharged provided they were in a good clinical condition and then either electively readmitted or managed as outpatients during the aplastic phase.
In 95/103 cycles (92%), discharge was feasible after a median of 7 (6-16) days. In 45 cycles, patients were electively readmitted at the onset of chemotherapy induced cytopenia after a median time of 12 (9-16) days. In 50 cycles, patients were managed as outpatients. In 23/50 outpatient cycles (46%), patients required rehospitalization, the main cause being neutropenic fever. There was 1 treatment related death due to sepsis in a patient in the outpatient group, accounting for an overall mortality of 2%. Transfusion requirements, occurrence of grade 3-4 toxicity, and disease free and overall survival after a median followup of 20 months did not differ between the treatment strategies. Comparison of diagnosis related group (DRG) proceeds revealed a 40% reduction with the outpatient strategy.
Outpatient management of consolidation therapy in selected AML patients appears to be feasible and safe and may reduce hospital treatment costs.
Onkologie 01/2010; 33(12):658-64. · 0.87 Impact Factor
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ABSTRACT: A number of single nucleotide polymorphisms (SNP) have been implicated to impact upon the disease course of chronic lymphocytic leukemia (CLL). However, few of these association studies could be confirmed in independent studies in the past. Recently, three independent studies did not confirm the prognostic impact of a new functional SNP in the BCL2 gene (-938C>A) described by Nückel et al. For this reason we genotyped an independent group of patients with CLL (n = 271) with mature follow up and detailed analysis of molecular genetics. The genotype distribution of this BCL2 polymorphism did not differ from that described in the original work. However, genotypes were not associated with time to first treatment (TFT) and overall survival (OS) in univariate or multivariate analysis in the current cohort. Comparing the characteristics of the two study cohorts in more detail we found differences between the two cohorts demonstrating a potentially more aggressive second study cohort. However, TFT and OS in patients with CLL according to Binet A did not differ significantly depending on the genotype. Our findings underscore the need for optimally matched patient cohorts in replication studies. The study re-emphasizes the need for large cohorts and validation in independent data sets before firm conclusions can be made about genotype-phenotype associations.
Leukemia & lymphoma 11/2009; 50(11):1837-42. · 2.40 Impact Factor
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ABSTRACT: Fc receptor-like 2 (FCRL2) is highly expressed on B-cell chronic lymphocytic leukemia (B-CLL) cells and could possibly influence disease pathogenesis. Therefore, we investigated FCRL2 mRNA expression in a large cohort with 152 CLL patients in order to assess its role in risk prediction in B-CLL. FCRL2 mRNA expression was found to be expressed at considerably higher levels in peripheral blood mononuclear cells (PBMC) of B-CLL patients compared to controls (range 1.35- to 210-fold upregulation; P < 0.0001) and cells of other hematological diseases. Patients with high FCRL2 expression (according to ROC-analysis) had a significantly longer treatment-free survival (TFS) and overall survival (OS) than patients with low FCRL2 expression (median TFS: 119 vs. 34 months, P < 0.0001; median OS: 321 months vs. not reached, P = 0.009). Univariate comparisons found that FCRL2 expression was weakly associated with IGHV mutation status (P = 0.05), CD38 status (P < 0.0001) and ZAP-70 status (P < 0.0001). Furthermore, we show that the combination of FCRL2 with ZAP70-, CD38- or IGHV-status could further significantly refine the prognostic information provided by either of the factors alone in TFS and OS. In multivariate analysis low FCRL2 expression was a significant independent prognostic factor (HR 2.4; P = 0.005). Here we demonstrate that the level of FCRL2 expression is correlated with prognosis in B-CLL.
European Journal Of Haematology 09/2009; 83(6):541-9. · 2.61 Impact Factor
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Stefanie Bug, Jan Dürig,
Florian Oyen,
Ludger Klein-Hitpass,
Jose I Martin-Subero,
Lana Harder,
Michael Baudis,
Norbert Arnold,
Uwe Kordes,
Ulrich Dührsen,
Reinhard Schneppenheim,
Reiner Siebert
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ABSTRACT: In T-cell prolymphocytic leukemia (T-PLL), chromosomal imbalances affecting the long arm of chromosome 22 are regarded as typical chromosomal aberrations secondary to a TCRAD-TCL1A fusion due to inv(14) or t(14;14). We analyzed recently obtained data from conventional karyotyping, SNP-chip array copy number mapping, genome-wide expression profiling, and interphase fluorescence in situ hybridization (FISH) of inv(14)-positive T-PLL with respect to structural aberrations on chromosome 22. Combined gene chip and interphase FISH analyses revealed interstitial deletions on 22q in 4 of 12 cases, with one case additionally showing a terminal copy number gain. A minimally deleted region of approximately 9.1 Mb was delineated, from 16.2 Mb (22cen) to 25.3 Mb (22q12.1). The distal borders of copy number alterations spread over a region of approximately 8.8 Mb, from 25.2 Mb (22q12.1) to 34 Mb (22q12.3). Mutation screening of candidate tumor suppressor genes SMARCB1 and CHEK2 mapping to the minimally deleted and the breakpoint regions, respectively, in cases with hemizygous deletion, revealed no inactivating mutations. With gene expression profiling, no significantly downregulated genes were identified in the minimally deleted region. We therefore assume that haploinsufficiency or alternative pathomechanisms underlie chromosome 22 aberrations in T-PLL.
Cancer genetics and cytogenetics 08/2009; 192(1):44-7. · 1.54 Impact Factor
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ABSTRACT: The objective of this study was to confirm previous results regarding the differential expression and prognostic significance of the circadian gene CRY1 in chronic lymphocytic leukemia (CLL) patients and its relationship with the expression of other circadian genes and well-established prognostic markers. We also aimed to investigate whether the peripheral circadian machinery may be deregulated in CLL cells. The expression of CRY1, PER1, and PER2 was determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in 116 CLL patients. The expression at sequential time points over a 24-h period was measured in six CLL patients and six normal donors. We confirmed the differential expression of CRY1 in ZAP-70(+)/CD38(+) and ZAP-70(-)/CD38(-) CLL samples. Subgroups formed according to CRY1 expression levels differed significantly in time to treatment. This difference was even more pronounced for subgroups stratified by a CRY1 : PER2 expression ratio and the ratio was an independent prognostic marker in a multivariate model. Furthermore, our data indicate disturbances in the periodic expression of circadian genes in CLL cells. Because of their role in the expression of cell cycle-related and DNA-damage response genes, we suggest that the deregulated expression of circadian genes may be linked to the molecular pathogenesis of CLL.
European Journal Of Haematology 07/2009; 83(4):320-7. · 2.61 Impact Factor
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Jose I Martin-Subero,
Ole Ammerpohl,
Marina Bibikova,
Eliza Wickham-Garcia,
Xabier Agirre,
Sara Alvarez,
Monika Brüggemann,
Stefanie Bug,
Maria J Calasanz,
Martina Deckert, [......],
José Román-Gómez,
Marc Seifert,
Harald Stein,
Javier Suela,
Lorenz Trümper,
Inga Vater,
Felipe Prosper,
Claudia Haferlach,
Juan Cruz Cigudosa,
Reiner Siebert
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ABSTRACT: Alterations in the DNA methylation pattern are a hallmark of leukemias and lymphomas. However, most epigenetic studies in hematologic neoplasms (HNs) have focused either on the analysis of few candidate genes or many genes and few HN entities, and comprehensive studies are required.
Here, we report for the first time a microarray-based DNA methylation study of 767 genes in 367 HNs diagnosed with 16 of the most representative B-cell (n = 203), T-cell (n = 30), and myeloid (n = 134) neoplasias, as well as 37 samples from different cell types of the hematopoietic system. Using appropriate controls of B-, T-, or myeloid cellular origin, we identified a total of 220 genes hypermethylated in at least one HN entity. In general, promoter hypermethylation was more frequent in lymphoid malignancies than in myeloid malignancies, being germinal center mature B-cell lymphomas as well as B and T precursor lymphoid neoplasias those entities with highest frequency of gene-associated DNA hypermethylation. We also observed a significant correlation between the number of hypermethylated and hypomethylated genes in several mature B-cell neoplasias, but not in precursor B- and T-cell leukemias. Most of the genes becoming hypermethylated contained promoters with high CpG content, and a significant fraction of them are targets of the polycomb repressor complex. Interestingly, T-cell prolymphocytic leukemias show low levels of DNA hypermethylation and a comparatively large number of hypomethylated genes, many of them showing an increased gene expression.
We have characterized the DNA methylation profile of a wide range of different HNs entities. As well as identifying genes showing aberrant DNA methylation in certain HN subtypes, we also detected six genes--DBC1, DIO3, FZD9, HS3ST2, MOS, and MYOD1--that were significantly hypermethylated in B-cell, T-cell, and myeloid malignancies. These might therefore play an important role in the development of different HNs.
PLoS ONE 01/2009; 4(9):e6986. · 4.09 Impact Factor
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ABSTRACT: Chronic lymphocytic leukemia (CLL) is characterized by a number of T-cell abnormalities, which may play a causative role in disease progression and immune dysfunction. Recently, expression levels of CD38 in T cells have been suggested as a novel adverse prognostic factor in male CLL patients. In the current study, CD38 expression on CLL T cells was examined by flow cytometry in 126 patients with B-CLL and correlated with clinical parameters and established molecular risk factors. In line with previous results we observed a positive correlation of CD38 expression on leukemic B and non-leukemic T cells with clinical stage. CD38 expression on B-CLL cells, cytogenetic aberrations and mutations of IgVH genes were found to significantly influence treatment-free survival. By contrast, CD38 expression on T cells was not significantly associated with an adverse clinical outcome.
Leukemia research 11/2008; 33(6):775-8. · 2.36 Impact Factor
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Benjamin Wilde,
Sebastian Dolff,
Xin Cai,
Christof Specker,
Jan Becker,
Martin Tötsch,
Ulrich Costabel, Jan Dürig,
Andreas Kribben,
Jan Willem Cohen Tervaert,
Kurt Werner Schmid,
Oliver Witzke
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ABSTRACT: An increased CD4(+) CD25(+) T-cell population is observed in Wegener's granulomatosis (WG). This T-cell population is not well characterized yet and their contribution to the disease pathogenesis remains obscure.
Thirty patients with WG and 18 healthy controls (HC) were included in this study. The disease activity and extension were measured by the Birmingham Vasculitis Activity Score (BVAS) and the Disease Extent Index (DEI). Lymphocytes from peripheral blood were analysed by FACS for the expression of CD4, CD25, CD134 and GITR. Cytokine expression in these subsets was assessed too. Nasal, lung and renal tissues from WG patients were immunohistochemically stained for CD3 and CD134.
The percentage of CD134(+) as well as GITR(+) expressing CD4(+)CD25(+) lymphocytes was increased in patients as compared to HC (37 +/- 12% versus 27 +/- 8%, P = 0.005; 18 +/- 9% versus 11 +/- 6%, P = 0.003). The expression of CD134 and GITR showed a significant correlation with disease activity (r = 0.5, P = 0.009; r = 0.55, P = 0.001). Most of these displayed the phenotype of effector memory T-cells (94 +/- 4% and 91 +/- 6%). CD134 T-cells were found in tissues affected by WG.
CD4(+)CD25(+) effector memory T-cells expressing CD134 and GITR seem to play a role in disease mechanisms, as suggested by their close association with disease activity and their participation in inflammatory process.
Nephrology Dialysis Transplantation 09/2008; 24(1):161-71. · 3.40 Impact Factor
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ABSTRACT: In contrast to other B-cell neoplasias, chronic lymphocytic leukaemia (CLL) is characterized by increased non-leukaemic T-cells. In order to assess their replicative history, telomere length was analyzed in subsets of leucocytes from CLL patients. Naive and memory T-cells from ZAP-70(+)/CD38(+) patients exhibited significantly shorter average telomere lengths than ZAP-70(-)/CD38(-) patients. Compared to the age-related percentiles of telomere length values from healthy individuals practically all values of the naive and memory T-cells from the ZAP-70(+)/CD38(+) CLL patients fell below the 50th percentile. This indicated an extensive expansion and a role for T-cells in ZAP-70(+)/CD38(+) CLL patients.
British Journal of Haematology 09/2008; 143(3):383-6. · 4.94 Impact Factor
