Torsten Witte

Hannover Medical School, Hanover, Lower Saxony, Germany

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Publications (198)995.05 Total impact

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    ABSTRACT: Objectives The diagnosis of extrapulmonary tuberculous infections and nontuberculous mycobacterial (NTM) infections is difficult because the symptoms are nonspecific and suitable specimens for bacterial culture are often not available. Recent publications reported the existence of autoantibodies in tuberculous infections. We screened for specific autoantibodies in mycobacterial infections.Methods We screened four in 29 patients with active mycobacterial infections and different controls using protein array technology. We could identify autoantibodies against ubiquitin-fold modifier-conjugating enzyme 1 (Ufc1) and pleckstrin homology domain containing, family G (with RhoGef domain) member 2 (Plekhg2) in all four patients. Subsequently, we designed enzyme-linked immunosorbent assays (ELISAs) for the detection of autoantibodies binding to Ufc1 and Plekhg2.ResultsAutoantibodies binding to Ufc1 and Plekhg2 were found in 19 of 29 patients (66%) with active mycobacterial infections. In comparison, we found these autoantibodies in one of 31 patients (3%) with successfully treated mycobacterial infections, in three of 40 (8%) HIV-infected patients not receiving combination antiretorviral therapy (cART) and in six of 134 (5%) blood donors. Interestingly, six of eight (75%) patients with HIV-associated B-cell non-Hodgkin lymphoma (B-NHL) at the onset of disease had autoantibodies against Ufc1 and Plekhg2, but none of nine (0%) patients after treatment of HIV-associated B-NHL, none of seven patients with non-HIV-associated B-NHL and 11 of 115 (10%) patients with other malignant diseases had autoantibodies against both proteins.Conclusions In view of the high frequency of these autoantibodies, we postulate that they might be of potential use for additional diagnostics for mycobacterial infections, and further studies may shed light on the pathomechanisms of these two autoantibodies.
    HIV Medicine 10/2014; · 3.16 Impact Factor
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    ABSTRACT: Takayasu arteritis (TA) is difficult to diagnose because diagnostic biomarkers have not yet been established. In a previous study, we detected autoantibodies against the human ferritin heavy chain protein (HFC) in the sera of patients with giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR). The aim of this study is to evaluate the frequency of autoantibodies against HFC in TA. We established seven ELISA assays for the detection of autoantibodies against HFC. We used the full-length recombinant HFC expressed in Escherichia coli or one of six different HFC peptides as autoantigens: 1-18Aa (98.8 % purity), 19-45Aa (98.8 % purity), 52-78Aa (98.3 % purity), 79-104Aa (98.8 % purity), 105-143Aa (98.4 % purity) and 145-183Aa (98.5 % purity). We collected sera from 48 patients with TA, 36 patients with systemic lupus erythematosus (SLE), 35 patients with arteriosclerosis, 133 patients with febrile diseases, which are known to generate unspecific autoantibodies, and 50 blood donors, which served as controls. The best results were obtained using the ferritin peptides as antigens. By combining the results from the different ELISAs that detect autoantibodies against the HFC peptides 19-44A, 79-104A and 105-144A, we were able to detect ferritin peptide antibodies in 30/48 (62 %) of the TA patients. The frequency was lower than in early GCA and PMR (previous study showed up to 92 %). Positive results were observed in 0/50 (0 %) of the control blood donors, 10/36 (28 %) of the SLE patients, 4/35 (11 %) of the arteriosclerosis patients and 27/133 (20 %) of the fever patients. Considering the lack of biomarkers for TA, autoantibodies against HFC peptides could act as useful markers for TA.
    Clinical rheumatology. 09/2014;
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    Arthritis & Rheumatology. 09/2014;
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    ABSTRACT: Heme oxygenase (HO)-1, the inducible isoform of HO, has immunomodulatory functions and is considered a target for therapeutic interventions. In the present study, we investigated whether modulation of HO-1 might have regulatory effects on in vitro T-cell activation. The study examined whether: (1) HO-1 induction by cobalt-protoporphyrin (CoPP) or inhibition by tin-mesoporphyrin (SnMP) can affect expansion and function of virus-specific T cells, (2) HO-1 modulation might have a functional effect on other cell populations mediating effects on proliferating T cells (e.g., dendritic cells (DCs), regulatory T cells (Tregs), and natural killer cells), and (3) HO-1-modulated antiviral T cells might be suitable for adoptive immunotherapy.Inhibition of HO-1 via SnMP in CMVpp65-peptide-pulsed PBMCs led to increased antiviral T-cell activation and the generation of a higher proportion of effector memory T cells (CD45RA– CD62L–) with increased capability to secrete IFN-γ and granzyme B. Treg depletion and SnMP exposure increased the number of antiviral T cells 15-fold.To test the possibility that HO-1 modulation might be clinically applicable in conformity with good manufacturing practice (GMP), SnMP was tested in isolated antiviral T cells using the cytokine secretion assay. Compared to control, SnMP treatment resulted in higher cell counts and purity without negative impact on quality and effector function (CD107a, IFN-γ, and TNF-α levels were stable).These results suggest an important role of HO-1 in the modulation of adaptive immune responses. HO-1 inhibition resulted in markedly more effective generation of functionally active T cells suitable for adoptive T-cell therapy.
    Clinical & Experimental Immunology 09/2014; · 3.41 Impact Factor
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    ABSTRACT: We aimed to replicate a recent study showing that genetic risk load at 15 loci was higher in men than in women with systemic lupus erythematosus (SLE). This difference was very significant and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE.
    Arthritis research & therapy. 06/2014; 16(3):R128.
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    ABSTRACT: OBJECTIVE: Different lines of evidence have highlighted the role of IL-17A in the inflammatory process occurring in giant cell arteritis (GCA). The aim of the present study was to assess whether the IL17A locus influences GCA susceptibility and its clinical subphenotypes. METHODS: We carried out a large meta-analysis including a total of 1266 biopsy-proven GCA patients and 3779 healthy controls from four European populations (Spain, Italy, Germany and Norway). Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were selected by tagging and genotyped using TaqMan assays. Allelic combination and dependency tests were also performed. RESULTS: In the pooled analysis, two of the five analysed polymorphisms showed evidence of association with GCA (rs2275913: PMH=1.85E-03, OR=1.17 (1.06-1.29); rs7747909: PMH=8.49E-03, OR=1.15 (1.04-1.27)). A clear trend of association was also found for the rs4711998 variant (PMH=0.059, OR=1.11 (1.00-1.23)). An independent effect of rs2275913 and rs4711998 was evident by conditional regression analysis. In addition, the haplotype harbouring the risk alleles better explained the observed association than the polymorphisms independently (likelihood p value <10-05). CONCLUSIONS: Polymorphisms within the IL17A locus show a novel association with GCA. This finding supports the relevant role of the Th17 cells in this vasculitis pathophysiology. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Annals of the Rheumatic Diseases 06/2014; · 9.11 Impact Factor
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    ABSTRACT: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with complex etiology. Loss of immune tolerance against self-antigens results in activation of the immune system to produce autoantibodies, which in turn contribute to the clinical manifestations of the disease. Immune cells harbor a plethora of regulatory receptors. Immunoglobulin-like transcripts (ILTs) exhibit both immune activation and inhibitory properties. Genetic defects in genes encoding these receptors may predispose to development of autoimmune diseases secondary to loss of their function. The aim of our study was to analyze the presence or absence of the 6.7 kb segment in the ILT6 gene and its association with susceptibility to SLE and its different manifestations.
    Lupus 06/2014; · 2.78 Impact Factor
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    ABSTRACT: Podocytes maintain the structure and function of the glomerular filtration barrier. However, lately podocytes have been implicated in the innate immune response and their function as non-hematopoietic antigen-presenting cells was highlighted. We have shown previously that excessive expression of the chemokine CXCL13 is a distinctive early event for nephritis in a murine model of systemic lupus erythematosus (SLE). Furthermore, we found that CXCL13 is significantly elevated in the serum of patients with SLE-Nephritis. Here, we were able to show for the first time, that 1) CXCL13 is expressed locally in glomeruli in a model for SLE-Nephritis in mice and that 2) incubation of human podocytes with CXCL13 induces receptor stimulation of CXCR5 with activation of signaling pathways, resulting in 3) secretion of pro-inflammatory cytokines and chemokines in culture supernatant. This cytokine/chemokine cocktail can lead to 4) a neutrophil respiratory burst in isolated human granulocytes. Taken together, our results provide further evidence that CXCL13 is involved in the pathogenesis of glomerulonephritis and that podocytes can play an active role in local proinflammatory immune responses. Thus, CXCL13 could be a direct target for the therapy of glomerulonephritis in general and for SLE-Nephritis in particular.
    Clinical & Experimental Immunology 05/2014; · 3.41 Impact Factor
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    ABSTRACT: De novo regeneration of immunity is a major problem after allogeneic hematopoietic stem cell transplantation (HCT). HCT modeling in severely compromised immune-deficient animals transplanted with human stem cells is currently limited because of incomplete maturation of lymphocytes and scarce adaptive responses. Dendritic cells (DC) are pivotal for the organization of lymph nodes and activation of naive T and B cells. Human DC function after HCT could be augmented with adoptively transferred donor-derived DC. In this study, we demonstrate that adoptive transfer of long-lived human DC coexpressing high levels of human IFN-α, human GM-CSF, and a clinically relevant Ag (CMV pp65 protein) promoted human lymphatic remodeling in immune-deficient NOD.Rag1(-/-).IL-2rγ(-/-) mice transplanted with human CD34(+) cells. After immunization, draining lymph nodes became replenished with terminally differentiated human follicular Th cells, plasma B cells, and memory helper and cytotoxic T cells. Human Igs against pp65 were detectable in plasma, demonstrating IgG class-switch recombination. Human T cells recovered from mice showed functional reactivity against pp65. Adoptive immunotherapy with engineered DC provides a novel strategy for de novo immune reconstitution after human HCT and a practical and effective tool for studying human lymphatic regeneration in vivo in immune deficient xenograft hosts.
    The Journal of Immunology 04/2014; · 5.52 Impact Factor
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    ABSTRACT: Objective: To investigate the role of the multifunctional protein Semaphorin 5A (Sema5A) in modulating cellular immune responses and as a biomarker in rheumatoid arthritis (RA). Methods: Soluble recombinant Sema5A was used to assess its effect on the functions of primary T and NK cells isolated from the peripheral blood of healthy donors. Cell proliferation and expression of transcription factors was determined by flow cytometry. Cytokine secretion was analysed by Luminex technology. Sera of 145 RA patients and control sera from healthy individuals or patients with non-RA rheumatic diseases were analysed for the presence of secreted Sema5A by ELISA and immunoblotting. Results: Soluble Sema5A strongly increased T- and NK-cell proliferation and induced the secretion of proinflammatory Th1/Th17 cytokines. Accordingly, Sema5A stimulation caused a significant upregulation of T-bet and RORγt levels in T cells. In addition, significantly elevated levels of secreted Sema5A were detected in the sera of RA patients compared to healthy controls. Sema5A levels were highest in RA patients positive for the RA biomarker anti-cyclic citrullinated peptide (p<0.001, compared to systemic lupus erythematosus and Sjögren syndrome patients) and correlated with levels of rheumatoid factor as a prototypical RA marker. Conclusion: Soluble Sema5A is a potent activator of T and NK cells in vitro and high Sema5A serum levels are associated with RA. Taken together, the results indicate that Sema5A contributes to the pathogenesis of RA through antigen-independent T- and NK-cell activation. Hence, Sema5A is a promising complementary biomarker for the diagnosis of RA. © 2014 American College of Rheumatology.
    Arthritis & rheumatology (Hoboken, N.J.). 02/2014;
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    ABSTRACT: Background Common variable immunodeficiency (CVID) is an antibody deficiency with an equal sex distribution and a high variability in clinical presentation. The main features include respiratory tract infections and their associated complications, enteropathy, autoimmunity, and lymphoproliferative disorders. Objective This study analyzes the clinical presentation, association between clinical features, and differences and effects of immunoglobulin treatment in Europe. Methods Data on 2212 patients with CVID from 28 medical centers contributing to the European Society for Immunodeficiencies Database were analyzed retrospectively. Results Early disease onset (<10 years) was very frequent in our cohort (33.7%), especially in male subjects (39.8%). Male subjects with early-onset CVID were more prone to pneumonia and less prone to other complications suggesting a distinct disease entity. The diagnostic delay of CVID ranges between 4 and 5 years in many countries and is particularly high in subjects with early-onset CVID. Enteropathy, autoimmunity, granulomas, and splenomegaly formed a set of interrelated features, whereas bronchiectasis was not associated with any other clinical feature. Patient survival in this cohort was associated with age at onset and age at diagnosis only. There were different treatment strategies in Europe, with considerable differences in immunoglobulin dosing, ranging from 130 up to 750 mg/kg/mo. Patients with very low trough levels of less than 4 g/L had poor clinical outcomes, whereas higher trough levels were associated with a reduced frequency of serious bacterial infections. Conclusion Patients with CVID are being managed differently throughout Europe, affecting various outcome measures. Clinically, CVID is a truly variable antibody deficiency syndrome.
    The Journal of allergy and clinical immunology 02/2014; · 12.05 Impact Factor
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    ABSTRACT: To perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease. Linkage disequilibrium (LD) mapping was conducted by using 1251 SNPs (single nucleotide polymorphism) covering a 862 kb genomic region on 3p14.3 comprising the PXK locus in 1467 SLE patients and 2377 controls of European origin. Tag SNPs and genotypes imputed with IMPUTE2 were tested for association by using SNPTEST and PLINK. The expression QTLs data included three independent datasets for lymphoblastoid cells of European donors: HapMap3, MuTHER and the cross-platform eQTL catalogue. Correlation analysis of eQTLs was performed using Vassarstats. Alternative splicing for the PXK gene was analysed on mRNA from PBMCs. Fine mapping revealed long-range LD (>200 kb) extended over the ABHD6, RPP14, PXK, and PDHB genes on 3p14.3. The highly correlated variants tagged an SLE-associated haplotype that was less frequent in the patients compared with the controls (OR=0.89, p=0.00684). A robust correlation between the association with SLE and enhanced expression of ABHD6 gene was revealed, while neither expression, nor splicing alterations associated with SLE susceptibility were detected for PXK. The SNP allele frequencies as well as eQTL pattern analysed in the CEU and CHB HapMap3 populations indicate that the SLE association and the effect on ABHD6 expression are specific to Europeans. These results confirm the genetic association of the locus 3p14.3 with SLE in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. We suggest a pathogenic mechanism mediated by the upregulation of ABHD6 in individuals carrying the SLE-risk variants.
    Annals of the rheumatic diseases 02/2014; · 8.11 Impact Factor
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    ABSTRACT: Hepatitis E virus (HEV) infection takes a clinically silent, self-limited course in the far majority of cases. Chronic hepatitis E has been reported in some cohorts of immunocompromised individuals. The role of HEV infections in patients with autoimmune hepatitis (AIH) is unknown. 969 individuals were tested for anti-HEV antibodies (MP-diagnostics) including 208 patients with AIH, 537 healthy controls, 114 patients with another autoimmune disease, rheumatoid arthritis (RA), and 109 patients with chronic HCV- or HBV-infection (HBV/HCV). Patients with AIH, RA and HBV/HCV were tested for HEV RNA. HEV-specific proliferative T cell responses were investigated using CFSE staining and in vitro stimulation of PBMC with overlapping HEV peptides. HEV-antibodies tested more frequently positive in patients with AIH (n = 16; 7.7%) than in healthy controls (n = 11; 2.0%; p = 0.0002), patients with RA (n = 4; 3.5%; p = 0.13) or patients with HBV/HCV infection (n = 2; 2.8%; p = 0.03). HEV-specific T cell responses could be detected in all anti-HEV-positive AIH patients. One AIH patient receiving immunosuppression with cyclosporin and prednisolone and elevated ALT levels had acute hepatitis E but HEV viremia resolved after reducing immunosuppressive medication. None of the RA or HBV/HCV patients tested HEV RNA positive. Patients with autoimmune hepatitis but not RA or HBV/HCV patients are more likely to test anti-HEV positive. HEV infection should been ruled out before the diagnosis of AIH is made. Testing for HEV RNA is also recommended in AIH patients not responding to immunosuppressive therapy.
    PLoS ONE 01/2014; 9(1):e85330. · 3.73 Impact Factor
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    ABSTRACT: Introduction: Although cardiac complications have been reported in established spondyloarthritis (SpA), little is known about peripheral axial SpA in large vessel vasculitis (LVV). The aim of this study was to assess the prevalence of SpA in patients with newly diagnosed LVV. Method: Retrospective single-centre analysis of all newly diagnosed LVV patients was performed between January 2011 and December 2012. Vasculitides were confirmed on thoracic magnetic resonance imaging (MRI) or 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). Patients completed a standardized questionnaire incorporating the Berlin criteria to assess inflammatory back pain. Existing scans were reassessed for sacroiliitis and ferritin antibodies measured in all patients. Results: Fifteen patients exhibiting new LVV were identified. Diagnosis was confirmed using MRI in nine patients and FDG-PET/CT in six. Six patients (40%) fulfilled American College of Rheumatology (ACR) criteria for giant cell arteritis (GCA) and polymyalgia rheumatica (PMR), and nine PMR only. Four patients fulfilled the Berlin criteria for inflammatory back pain, with three demonstrating sacroiliitis on imaging. All remaining patients demonstrated no sacroiliitis. One further patient with LVV lacking features of inflammatory back pain had known psoriatic arthritis (PsA). Patients with coexisting SpA were younger (mean age 57 years vs. 66 years) and had higher C-reactive protein (CRP) levels (200 mg/L vs. 85 mg/L) at presentation. Four SpA patients and seven out of nine patients with isolated LVV had ferritin antibodies. Conclusions: We have demonstrated a higher than anticipated prevalence of SpA in LVV, given the reported 0.5-1% prevalence in the general population. Coexisting SpA should be considered in LVV patients exhibiting inflammatory back pain despite steroid initiation. Ferritin antibodies demonstrated a similarly high prevalence in aortitis and SpA as reported previously in untreated GCA and PMR.
    Scandinavian journal of rheumatology 01/2014; · 2.51 Impact Factor
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    ABSTRACT: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants using a follow-up strategy. Sixty six non-HLA SNPs showing a P-value < 10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study performing a meta-analysis which combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed using TaqMan SNP genotyping assays. We observed nominal associations for both PPARG rs310746 (PMH = 1.90 x 10-6, OR = 1.28) and CHRNA9 rs6832151 (PMH = 4.30 x 10-6, OR = 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P-value = 0.066, OR = 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome wide significant P-value (PMH = 5.00 x 10-7, OR = 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled-analysis. Our results suggest a role of PPARG gene in the development of SSc.
    Arthritis research & therapy 01/2014; 16(1):R6. · 4.27 Impact Factor
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    ABSTRACT: In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, pro- vided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.
    The American Journal of Human Genetics 01/2014; 94:47-61. · 11.20 Impact Factor
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    ABSTRACT: Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune diseases, and have been determined by indirect immunofluorescence assay (IIFA) for decades. As the demand for ANA testing increased, alternative techniques were developed challenging the classic IIFA. These alternative platforms differ in their antigen profiles, sensitivity and specificity, raising uncertainties regarding standardisation and interpretation of incongruent results. Therefore, an international group of experts has created recommendations for ANA testing by different methods.Two groups of experts participated in this initiative. The European autoimmunity standardization initiative representing 15 European countries and the International Union of Immunologic Societies/World Health Organization/Arthritis Foundation/Centers for Disease Control and Prevention autoantibody standardising committee. A three-step process followed by a Delphi exercise with closed voting was applied.Twenty-five recommendations for determining ANA (1-13), anti-double stranded DNA antibodies (14-18), specific antibodies (19-23) and validation of methods (24-25) were created. Significant differences between experts were observed regarding recommendations 24-25 (p<0.03). Here, we formulated recommendations for the assessment and interpretation of ANA and associated antibodies. Notably, the roles of IIFA as a reference method, and the importance of defining nuclear and cytoplasmic staining, were emphasised, while the need to incorporate alternative automated methods was acknowledged. Various approaches to overcome discrepancies between methods were suggested of which an improved bench-to-bedside communication is of the utmost importance. These recommendations are based on current knowledge and can enable harmonisation of local algorithms for testing and evaluation of ANA and related autoantibodies. Last but not least, new more appropriate terminologies have been suggested.
    Annals of the rheumatic diseases 10/2013; · 8.11 Impact Factor
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    ABSTRACT: Sjögren's syndrome is a common autoimmune disease (affecting ∼0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjögren's syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (Pmeta = 7.65 × 10(-114)), we establish associations with IRF5-TNPO3 (Pmeta = 2.73 × 10(-19)), STAT4 (Pmeta = 6.80 × 10(-15)), IL12A (Pmeta = 1.17 × 10(-10)), FAM167A-BLK (Pmeta = 4.97 × 10(-10)), DDX6-CXCR5 (Pmeta = 1.10 × 10(-8)) and TNIP1 (Pmeta = 3.30 × 10(-8)). We also observed suggestive associations (Pmeta < 5 × 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjögren's syndrome.
    Nature Genetics 10/2013; · 35.21 Impact Factor
  • D Ernst, R E Schmidt, T Witte
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    ABSTRACT: Immunosuppressive treatment plays a crucial role in the management of autoimmune and autoinflammatory diseases. Knowledge about the ensuing immune deficits resulting from these therapies as well as common infections in immunocompromised patients should be familiar to all doctors involved in the prescription and administration of immunosuppressive drugs. Comprehensive pretreatment screening, regular monitoring both during and following treatment as well common sense preventive measures, such as vaccination can help further minimise the risk of infection.
    Zeitschrift für Rheumatologie 08/2013; · 0.45 Impact Factor
  • Zeitschrift für Rheumatologie 08/2013; · 0.45 Impact Factor

Publication Stats

2k Citations
995.05 Total Impact Points


  • 1990–2014
    • Hannover Medical School
      • • Clinic for Immunology and Rheumatology
      • • Institute for Clinical Chemistry
      • • Department of Gastroenterology, Hepatology and Endocrinology
      Hanover, Lower Saxony, Germany
  • 2010–2013
    • The University of Manchester
      Manchester, England, United Kingdom
    • Hospital Clínico San Carlos
      • Servicio de Neurología
      Madrid, Madrid, Spain
  • 2007–2013
    • Spanish National Research Council
      • Institute of Parasitology and Biomedicine "López-Neyra"
      Madrid, Madrid, Spain
    • University of Leipzig
      • Medizinische Fakultät
      Leipzig, Saxony, Germany
  • 2012
    • Oklahoma Medical Research Foundation
      • Arthritis and Clinical Immunology Program
      Oklahoma City, OK, United States
  • 2011–2012
    • Instituto de Investigación Sanitaria de Santiago de Compostela
      Santiago, Galicia, Spain
    • University of Texas MD Anderson Cancer Center
      • Department of Epidemiology
      Houston, TX, United States
  • 2007–2012
    • Uppsala University
      • The Rudbeck Laboratory
      Uppsala, Uppsala, Sweden
  • 2007–2009
    • University of Santiago de Compostela
      Santiago, Galicia, Spain
  • 2003–2004
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
    • Sheba Medical Center
      • Department of Medicine B
      Gan, Tel Aviv, Israel
    • Historisches Museum Hannover
      Hanover, Lower Saxony, Germany
  • 1995
    • Harvard Medical School
      Boston, Massachusetts, United States
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
  • 1993
    • University of Hamburg
      Hamburg, Hamburg, Germany