Sonja Gudowius

Universitätsklinikum Düsseldorf, Düsseldorf, North Rhine-Westphalia, Germany

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Publications (21)156.66 Total impact

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    ABSTRACT: Siepermann M, Gudowius S, Beltz K, Strier U, Feyen O, Troeger A, Göbel U, Laws HJ, Kögler G, Meisel R, Dilloo D, Niehues T. MHC class II deficiency cured by unrelated mismatched umbilical cord blood transplantation: Case report and review of 68 cases in the literature. Pediatr Transplantation 2011: 15: E80–E86. © 2010 John Wiley & Sons A/S. Abstract: MHC class II deficiency is a rare and fatal form of primary combined immunodeficiency caused by a lack of T-cell-dependent humoral and cellular immune response to foreign antigens, which can only be cured by allogenic stem cell transplantation. In the literature search, we identified 68 cases of HSCT in MHC class II deficiency in the last 14 yr. Pre- and post-transplant MHC class II deficiency is complicated by overwhelming viral infections, a high incidence of GvHD, and graft failure with a poor overall survival rate below 50%. We report an eight-month-old boy presenting with severe respiratory infections and chronic diarrhea, whose sister died at the age of four yr from septicemia. MHC II deficiency was caused by an RFXANK-mutation and treated successfully by 4/6 mismatched unrelated CBT after a myeloablative conditioning regimen based on anti-thymocyte globulin, busulfane, fludarabine, and cyclophosphamide. At present, our patient is well with full immune reconstitution 3 yr after CBT. CB may represent an alternative source of stem cells for children with MHC class II deficiency without a suitable donor.
    Pediatric Transplantation 03/2010; 15(4):E80-6. DOI:10.1111/j.1399-3046.2010.01292.x · 1.63 Impact Factor
  • Zeitschrift für Geburtshilfe und Neonatologie 04/2009; 213. DOI:10.1055/s-0029-1223043 · 0.46 Impact Factor
  • Zeitschrift für Geburtshilfe und Neonatologie 04/2009; 213. DOI:10.1055/s-0029-1223039 · 0.46 Impact Factor
  • Zeitschrift für Geburtshilfe und Neonatologie 04/2009; 213. DOI:10.1055/s-0029-1223051 · 0.46 Impact Factor
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    ABSTRACT: Haematopoietic stem cell transplantation is the treatment of choice for severe primary immunodeficiencies, but only has moderate prognosis in Omenn syndrome as it is complicated by highly activated Omenn T-cells resulting in delayed T-cell engraftment and a high rate of graft failure. A 6 1/2 months old patient with a previously unknown compound heterozygous defect within the RAG1 gene (R474C; R975W) underwent 8/10 HLA-matched cord blood transplantation after myeloablative conditioning. Immune reconstitution was impressive with T-, B- and NK-cells reaching the median of age-dependent reference values within twelve, four and two months respectively. With a continuous decrease of activated Omenn T-cells there was a steady increase of naive, probably thymus-derived T-cells. Polyclonal B-cell activation and hypergammaglobulinaemia disappeared with B-cell engraftment. This case emphasizes that, despite their naive status and HLA-barriers, cord blood T-cells were apparently able to achieve T-effector function resulting in the elimination of all activated Omenn T-cells.
    Clinical Immunology 03/2009; 130(3):259-63. DOI:10.1016/j.clim.2008.09.018 · 3.99 Impact Factor
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    ABSTRACT: We describe three unrelated girls who had an immunodeficiency disease with granulomas in the skin, mucous membranes, and internal organs. All three girls had severe complications after viral infections, including B-cell lymphoma associated with Epstein-Barr virus (EBV). Other findings were hypogammaglobulinemia, a diminished number of T and B cells, and sparse thymic tissue on ultrasonography. Molecular analysis revealed that the patients were compound heterozygotes for mutations in recombination activating gene 1 or 2 (RAG1 or RAG2). In each case, both parents were heterozygous carriers of a RAG mutation. The mutations were associated with reduced function of RAG in vitro (3 to 30% of normal activity). The parents and one sibling in the three families were healthy.
    New England Journal of Medicine 06/2008; 358(19):2030-8. DOI:10.1056/NEJMoa073966 · 54.42 Impact Factor
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    New England Journal of Medicine 01/2008; · 54.42 Impact Factor
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    ABSTRACT: Nerve growth factor (NGF) plays a pivotal role in cellular survival/death decisions with the low affinity receptor p75NTR predominately transmitting anti-proliferative signals. In spite of its established role in B-cell function and identification as a prognostically favourable marker in a number of malignancies, little is known about the expression pattern and prognostic significance of p75NTR in B cell precursor-acute lymphoblastic leukaemia (BCP-ALL). p75NTR expression was prospectively studied on primary ALL-blasts in a cohort of paediatric patients with common ALL (n = 86) and preB-ALL (n = 34) treated within the Co-operative study group for childhood acute lymphoblastic leukaemia (CoALL) protocol, CoALL06-97. Flow cytometric analysis showed that almost half of the patients expressed no or negligible amounts of p75NTR (<10%). The median expression in patients expressing p75NTR beyond that threshold was 49% (range 11-100%). In patients classified as low-risk at diagnosis, p75NTR expression was significantly higher than in high-risk patients (P = 0.001). Of note, p75NTR expression was lower in the 21 patients who subsequently developed relapse compared with those remaining in remission (P = 0.038). Accordingly, relapse-free survival was significantly better in patients expressing high surface p75NTR (P = 0.041). Thus, in this prospective analysis, high p75NTR expression was a strong prognostic marker that identified a group of paediatric ALL patients with favourable outcome.
    British Journal of Haematology 12/2007; 139(3):450-7. DOI:10.1111/j.1365-2141.2007.06818.x · 4.96 Impact Factor
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    ABSTRACT: Impaired apoptosis, mediated by members of the inhibitor of apoptosis proteins (IAP) family such as survivin, is thought to contribute to leukemic cell survival. In contrast to low expression of survivin in normal differentiated adult tissues, very high levels of survivin have been described in a number of different tumors. Overexpression of survivin was found to correlate with poor prognosis in a variety of cancers including hematologic malignancies. To date, however, there is no information available on the prognostic role of survivin in pediatric precursor B-cell acute lymphocytic leukemia (BCP-ALL), the most frequent malignancy in childhood. In a retrospective study including 66 pediatric patients we analyzed the impact of survivin protein levels on outcome in BCP-ALL. Survivin overexpression, with an up to ten-fold increase of the normal level, was detected in 65% of the leukemic samples in contrast to negligible expression in non-malignant hematopoietic cells. Despite considerable variety of expression levels in ALL cells, there was no association of survivin levels with established risk factors. However, patients suffering relapse of disease or death had significantly higher survivin expression than those with a favorable outcome. Overexpression of survivin is a significant prognostic marker for 3 year relapse free, event-free and overall survival, again independent of the established prognostic factors in ALL, such as age and leukocyte count at diagnosis as assessed in multivariate analysis. Overexpression of survivin in BCP-ALL identifies patients with a high risk of early relapse. Upon confirmation in a prospective analysis, survivin expression may, in the future, serve to further refine treatment stratification with intensification of therapy in those patients prone to relapse.
    Haematologica 09/2007; 92(8):1043-50. DOI:10.3324/haematol.10675 · 5.87 Impact Factor
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    ABSTRACT: To understand how corticosteroids act; a characterization of their effects on lymphocytes is necessary. The effect of in vivo corticosteroids on lymphocyte subpopulations, their surface molecules and externalization of phosphatidylserine (apoptosis) is examined. In a crossover study, a single, intravenous dose of 2 mg/kg prednisolone or saline was given to six male adult human volunteers. Blood samples were withdrawn before and 30 min, 2, 5, 23 and 29 h thereafter. Lymphocyte subsets were determined by FACS analysis. Externalization of phosphatidylserine was measured by Annexin-V; cell fragments were excluded by propidium iodide staining. Lymphocyte number decreased from 2,007 +/- 473 to 634 +/- 119 microl after 5 h and rose to 3,112 +/- 436 microl after 23 h. CD4, CD8 and B cell counts declined significantly after 5 h (P < or = 0.01). The expression of CD28 or CD95 on T cells and the natural killer cells were unaffected. There was a significant rebound of lymphocyte numbers above baseline 23 h after prednisolone. At baseline 9.9 +/- 3.8% of cells in the lymphocyte gate did not stain for CD3, CD20 or CD56 (referred to as "null cells"). 5 h after application of prednisolone, there was a significant increase of "null cells" (28 +/- 12%, P = 0.018). The percentage of phosphatidylserine positive CD4 cells rose from 8.1 +/- 3.3 to 19.8 +/- 8% after intravenous prednisolone, while the percentage of phosphatidylserine positive CD8, B and NK cells remained largely unchanged. Prednisolone induces a most significant depletion of CD4 cells, which to some degree is associated with apoptosis. The net increase of lymphocyte numbers 23 h after prednisolone application may be a beneficial late effect of a single i.v. prednisolone shot.
    Rheumatology International 05/2007; 27(7):667-73. DOI:10.1007/s00296-007-0319-4 · 1.63 Impact Factor
  • Klaus Bienemann · Sonja Gudowius · Tim Niehues
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    ABSTRACT: The Wiskott-Aldrich syndrome is a rare X-linked immunodeficiency characterized by microplatelet thrombocytopenia and eczema. Eczema may be severe and facilitate entry of microorganism into the host. Conclusion: We report for the first time that eczema in infants with WAS can be effectively treated with topical tacrolimus.
    Acta Paediatrica 03/2007; 96(2):312-4. DOI:10.1111/j.1651-2227.2007.00044.x · 1.84 Impact Factor
  • S Gudowius · A von der Wense · T Niehues
    Zeitschrift für Geburtshilfe und Neonatologie 01/2007; 211. DOI:10.1055/s-2007-983290 · 0.46 Impact Factor
  • S. Gudowius · T. Niehues
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    ABSTRACT: Das klinische Bild des systemischen Lupus erythematodes ist heterogen. Allgemeinsymptome wie Fieber, Müdigkeit, Lymphknotenschwellung und Gewichtsverlust können einer systemischen Organmanifestation vorausgehen und die Diagnose erschweren. Charakteristisch sind Hautveränderungen wie das Schmetterlingserythem, Beteiligungen von Gelenken, Nieren, ZNS und Hämatopoese sind häufig. Infolge von Organschäden oder schweren Infektionen kann der SLE lebensbedrohlich sein. Bei den Laboruntersuchungen sind in vielen Fällen eine Blutsenkungsbeschleunigung, eine Hypokomplementämie und der Nachweis von antinukleären, insbesondere Anti-Doppelstrang-DNA-Antikörpern diagnostisch wegweisend. Der vorliegende Beitrag gibt eine Übersicht über die klinischen Manifestationen und das diagnostische Prozedere des SLE im Kindesalter.
    Monatsschrift Kinderheilkunde 12/2006; 154(12). DOI:10.1007/s00112-006-1438-9 · 0.28 Impact Factor
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    ABSTRACT: Contemporary risk adapted treatment protocols for childhood acute lymphoblastic leukemia (ALL) rely on accurate risk assessment strategies for disease re-occurrence by incorporating clinical parameters as well as immunological, molecular and cytogenetic features of the blasts at initial manifestation. Additional risk stratification is provided by analysis of the IN VITRO and IN VIVO response of the blasts towards standard chemotherapy. Despite adapted therapies, a number of children with good and bad prognostic factors still fail therapy. One approach to this problem might be to incorporate monoclonal antibodies (MoAbs) as additional modalities into the first or second line treatment. In order to identify target antigen structures, we analyzed the immunological expression profiles of blasts from 181 patients with B-cell precursor ALL treated at our institution in 11 years according to the CoALL-92/97/03 protocols. Blasts were classified according to the EGIL guidelines as 9 proB-, 110 common (c-) and 62 preB-ALL. > 99 and 96 % of patients expressed CD19 and CD22 on > 90 % of their blasts, respectively. HLA-DR on > 95 % blasts was present in all patients. CD10 was expressed on all c-/preB-ALL and absent on proB-ALL cells. CD20 was expressed on 11-37 % of B-cell precursor ALL samples. CD34 positive blasts were found in 89, 83 and 68 % of patients with proB-, c- and preB-ALL, respectively. CD37 expression was detected in 0-18 % of patients. < 20 % CD45(+) blasts were found in 11, 19 and 18 % of patients with proB-, c- and preB-ALL. CD33(+) was expressed on 33, 29 and 21 % of patients samples with proB-, c- and preB-ALL. Other myeloid antigens (CD13, CD14, CD15, CD65) were positive on blasts in < 25 % of patients. Analyses of the immunological profile of blasts in 9 consecutive children with relapse revealed that the antigen expression profile varied little compared to the initial diagnosis for CD10, CD19, CD22 and HLA-DR. These analyses clearly identified the three antigens CD19, CD22 and HLA-DR present on blasts in more than 90 % of patients as potential target structures for targeted therapies with native or toxin-bound monoclonal antibodies in childhood ALL.
    Klinische Pädiatrie 11/2006; 218(6):327-33. DOI:10.1055/s-2006-942273 · 1.90 Impact Factor
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    British Journal of Haematology 11/2006; 135(1):139-40. DOI:10.1111/j.1365-2141.2006.06263.x · 4.96 Impact Factor
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    ABSTRACT: Fanconi anaemia (FA) is a rare recessive DNA repair disorder clinically characterised by congenital malformations, progressive bone marrow failure and a high propensity for developing malignancies at an early age, predominantly acute myeloid leukaemia (AML) and squamous cell carcinoma. It is conceivable that a number of patients with hypomorphic mutations are not diagnosed as FA until severe complications in the treatment of a malignancy occur. Here, we report on a patient with FA-A, diagnosed only at the age of 49 years due to persistent pancytopenia and myelodysplastic syndrome/AML induced by a first cycle of chemotherapy for bilateral metachronic breast cancer. This exceptional case clearly demonstrates that, in instances of long-lasting mild pancytopenia or development of malignancies, especially at an unusually young age, FA should be ruled out, irrespective of the patient's age and features, especially before inflicting severe genotoxic stress.
    British Journal of Haematology 05/2006; 133(2):188-97. DOI:10.1111/j.1365-2141.2006.05998.x · 4.96 Impact Factor
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    ABSTRACT: We describe the development of a localized Mycobacterium bovis-BCG infection in association with insertion of HAART in an 18-month-old HIV-infected and BCG-vaccinated child.
    Infectious Diseases 02/2006; 38(8):716-8. DOI:10.1080/00365540500452473 · 1.64 Impact Factor
  • S. Gudowius · T. Niehues
  • K Gensch · S Gudowius · T Niehues · A Kuhn
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    ABSTRACT: Connective tissue diseases are a heterogeneous group of chronic multisystem inflammatory disorders including systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS), dermato- (DM) and polymyositis (PM), mixed connective tissue disease (MCTD), and Sjögren's syndrome (SS). Patients can present with similar clinical features, particularly during the first onset of symptoms, which frequently makes the diagnosis of a specific disease difficult. The incidence of connective tissue diseases is much lower in children than adults; however, the clinical picture is more variable. Clinical signs, such as fatigue, fever, or weight loss, may precede any systemic organ involvement and in children, mucocutaneous manifestations develop most frequently during the varying disease course. This review summarizes recent information on epidemiology, clinical manifestations, diagnostic procedures, and treatment strategies of the different connective tissue diseases, concentrating on specific problems in childhood.
    Der Hautarzt 11/2005; 56(10):925-36. · 0.54 Impact Factor
  • K. Gensch · S. Gudowius · T. Niehues · A. Kuhn
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    ABSTRACT: Zusammenfassung Kollagenosen umfassen eine heterogene Gruppe von chronisch entzündlichen Multiorganerkrankungen, die den systemischen Lupus erythematodes (SLE), die progressiv systemische Sklerodermie (PSS), die Dermato- (DM) und Polymyositits (PM) sowie die gemischte Bindegewebserkrankung („mixed connective tissue disease“, MCTD) und das Sjögren-Syndrom (SS) einschließen. Insbesondere zu Beginn der jeweiligen Erkrankung können die Patienten ähnliche klinische Symptome aufweisen, die häufig eine spezifische Diagnose erschweren. Im Kindesalter ist die Inzidenz der Kollagenosen wesentlich niedriger als bei Erwachsenen, aber die Krankheitsbilder zeigen eine größere morphologische Vielfältigkeit. Allgemeinsymptome wie Müdigkeit, Fieber und Gewichtsverlust können einer systemischen Organmanifestation vorausgehen, und während des rezidivierenden Verlaufs der Erkrankungen entwickeln sich bei Kindern am häufigsten mukokutane Manifestationen. In diesem Übersichtsartikel werden die neuesten Angaben über Epidemiologie, klinische Manifestationen, diagnostisches Prozedere und therapeutische Strategien der Kollagenosen zusammengefasst und spezifische Probleme im Kindesalter dargestellt.
    Der Hautarzt 10/2005; 56(10):925-936. DOI:10.1007/s00105-005-1016-4 · 0.54 Impact Factor