Browsing by Author "Ehl, Stephan"

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Clinical presentation and long-term outcome of DOCK8 deficiency - a survey of 134 patients
(Springer/Plenum Publishers, 2012-09) Albert, M.; Aydın, S.; Su, H.; Chatila, T.; Alsum, Z.; Heinz, V.; Al-Herz, W.; Keleş, S.; Picard, C.; Gathmann, B.; Hoenig, M.; Gennery, A.; Al-Mousa, Hamoud; Geha, R. S.; Sawalle-Belohradsky, J.; Notheis, G.; Schwarze, C. P.; Metin, A.; Gaspar, B.; Bienemann, K.; Schulz, A.; Thiel, J.; Dueckers, G.; Kuijpers, T. W.; van Montfrans, J. M.; Ifversen, Marianne; Barlogis, V.; Hawwari, Abbas; Holland, S. M.; Rezaei, Nima; Al Zahrani, D.; Genel, F.; Kostyuchenko, Larysa; Kainulainen, L.; Porras, O.; Kumar, A.; Ehl, Stephan; Aytekin, C.; Gonzalez-Granado, Luis Ignacio; Abbott, Jordan K.; Kütükçüler, N.; Marodi, Laszlo; Grimbacher, B.; Renner, Ellen D.; Ochs, H.; Belohradsky, B. H.; Sanal, O.; Freeman, A. F.; Engelhardt, K. R.; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı/Çocuk İmmünolojisi Bölümü.; 0000-0001-8571-2581; AAH-1658-2021
Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome
(Mosby-Elsevier, 2010-02) Woellner, Cristina; Gertz, Edward Michael; Schaffer, Alejandro A.; Lagos, Macarena; Perro, Mario; Glocker, Erik Oliver; Pietrogrande, Maria Cristina; Cossu, Fausto; Franko, Josè Luis; Matamoros, Núria; Pietrucha, Barbara Maria; Heropolitańska-Pliszka, Edyta; Yeganeh, Mehdi; Moin, Mostafa; Español, Theresa; Ehl, Stephan; Gennery, Andrew R.; Abinun, Mario A.; Brȩborowicz, Anna; Niehues, Tim; Junker, Anne K.; Turvey, Stuart E.; Plebani, Alessandro; Sánchez, Berta; Garty, Ben Zion; Pignata, Claudio; Cancrini, Caterina; Litzman, Jiří; Sanal, Özden; Baumann, Ulrich; Bacchetta, Rosa; Hsu, Amy P.; Davis, Joie N.; Hammarström, Lennart L.G.; Davis, Edward Graham; Eren, Efrem; Arkwright, Peter D.; Moilanen, Jukka S.; Viemann, Dorothee; Khan, Sujoy; Máródi, László D.R.; Cant, Andrew James; Freeman, Alexandra F.; Puck, Jennifer M.; Holland, Steven M.; Grimbacher, Bodo; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.; 0000-0001-8571-2581; AAH-1658-2021; 34975059200
Background: The hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by infections of the lung and skin, elevated serum IgE, and involvement of the soft and bony tissues. Recently, HIES has been associated with heterozygous dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT-3) and severe reductions of T(H)17 cells. Objective: To determine whether there is a correlation between the genotype and the phenotype of patients with HIES and to establish diagnostic criteria to distinguish between STAT3 mutated and STAT3 wild-type patients. Methods: We collected clinical data, determined T(H)17 cell numbers, and sequenced STAT3 in 100 patients with a strong clinical suspicion of HIES and serum IgE > 1000 IU/mL. We explored diagnostic criteria by using a machine-learning approach to identify which features best predict a STAT3 mutation. Results: In 64 patients, we identified 31 different STAT3 mutations, 18 of which were novel. These included mutations at splice sites and outside the previously implicated DNA-binding and Src homology 2 domains. A combination of 5 clinical features predicted STAT3 mutations with 85% accuracy. T(H)17 cells were profoundly reduced in patients harboring STAT-3 mutations, whereas 10 of 13 patients without mutations had low (<1%) T(H)17 cells but were distinct by markedly reduced IFN-gamma-producing CD4(+)T cells. Conclusion: We propose the folio-wing diagnostic guidelines for STAT3-deficient HIES. Possible: IgE >1000IU/mL plus a weighted score of clinical features >30 based on recurrent pneumonia, newborn rash, pathologic bone fractures, characteristic face, and high palate. Probable: These characteristics plus lack of T(H)17 cells or a family history for definitive HIES. Definitive: These characteristics plus a dominant-negative heterozygous mutation in STAT3.
Mutations in the signal transducer and activator of transcription 3 (STAT3) and diagnostic guidelines for the Hyper-IgE Syndrome
(Wiley, 2010-04) Woellner, Cristina; Gertz, M. E.; Schaffer, Alejandro; Lagos, Macarena; Perro, Mario; Glocker, Erik-Oliver; Pietrogrande, Maria Cristina; Cossu, Fausto; Marin Franco, Jose Luis; Matamoros, N.; Pietrucha, Bernard; Heropolitanska-Pliszka, Edyta; Yeganch, M.; Rezaei, Nima; Espanol, Teresa; Ehl, Stephan; Gennery, Andrew R.; Abinun, Mario; Breborowicz, Anna; Niehues, Tim; Junker, Anne K.; Turvey, Stuart E.; Plebani, Alessandro; Sanchez, Berta Erika Luis; Garty, Ben Zion; Pignata, Claudio; Cancrini, Caterina; Litzman, Jiří; Sanal, Özden; Batimann, U.; Bacchetta, Rosa; Hsu, Amy P.; Davis, Joie N.; Hammarström, Lennart L.G.; Davis, Edward Graham; Eren, Efrem; Arkwright, Peter D.; Moilanen, Jukka S.; Viemann, Dorothee; Khan, Sujoy; Máródi, László D.R.; Cant, Andrew James; Freeman, Alexandra F.; Puck, Jennifer M.; Holland, Steven M.; Grimbacher, Bodo; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.; AAH-1658-2021
Simple measurement of iga predicts immunity and mortality in ataxia-telangiectasia
(Springer/plenum Publishers, 2021-09-03) Zielen, Stefan; Duecker, Ruth Pia; Woelke, Sandra; Donath, Helena; Bakhtiar, Sharhzad; Buecker, Aileen; Kreyenberg, Hermann; Huenecke, Sabine; Bader, Peter; Mahlaoui, Nizar; Ehl, Stephan; El-Helou, Sabine M.; Pietrucha, Barbara; Plebani, Alessandro; van der Flier, Michiel; van Aerde, Koen; Reda, Shereen M.; Kostyuchenko, Larysa; McDermott, Elizabeth; Galal, Nermeen; Pignata, Claudio; Perez, Juan Luis Santos; Laws, Hans-Juergen; Niehues, Tim; Kutukculer, Necil; Seidel, Markus G.; Marques, Laura; Ciznar, Peter; Edgar, John David M.; Soler-Palacin, Pere; von Bernuth, Horst; Krueger, Renate; Meyts, Isabelle; Baumann, Ulrich; Kanariou, Maria; Grimbacher, Bodo; Hauck, Fabian; Graf, Dagmar; Granado, Luis Ignacio Gonzalez; Prader, Seraina; Reisli, Ismail; Slatter, Mary; Rodriguez-Gallego, Carlos; Arkwright, Peter D.; Bethune, Claire; Deripapa, Elena; Sharapova, Svetlana O.; Lehmberg, Kai; Davies, E. Graham; Schuetz, Catharina; Kindle, Gerhard; Schubert, Ralf; Kilic, Sara S.; KILIÇ GÜLTEKİN, SARA ŞEBNEM; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.
Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naive CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ss repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978)
Toll-like receptor stimulation induces higher tnf-α secretion in peripheral blood mononuclear cells from patients with hyper ige syndrome
(Karger, 2008-01-01) Yeganeh, Mehdi; Henneke, Philipp; Rezaei, Nima; Ehl, Stephan; Thiel, Doerte; Matamoros, Nuria; Pietrogrande, Cristina; Espanol, Teresa; Litzman, Jiri; Franco, Jose L.; Sanal, Ozden; Kılıç, Sara S.; Breborowicz, Anna; Plebani, Alessandro; Renner, Ellen; Rothenfusser, Simon; Hawn, Thomas R.; Woellner, Cristina; Grimbacher, Bodo; KILIÇ GÜLTEKİN, SARA ŞEBNEM; Uludağ Üniversitesi/Tıp Fakültesi/Pediatrik İmmünoloji Anabilim Dalı.; 0000-0002-9454-1603; 0000-0002-1926-5426; 0000-0001-8571-2581; 0000-0002-5398-1717; 0000-0001-9816-8538; 0000-0002-6897-6806; AAH-1658-2021
Hyper IgE syndromes (HIES) are primary immunodeficiency disorders of unknown pathogenesis. Patients are typically affected with 'cold' abscesses of the skin, recurrent cyst-forming pneumonia, chronic mucocutaneous candidiasis and other less frequent features such as progressive skeletal abnormalities. Defective signaling in the Toll-like receptor (TLR) pathways has been suggested as a responsible pathologic mechanism, however, in previous reports, 10 patients revealed no defect in inflammatory cytokine responses to different TLR ligands. Here, we report the increase in pro-inflammatory cytokines TNF-alpha and IL-8, following TLR2 and TLR4 stimulation in a larger cohort of 25 additional patients with HIES, and provide a meta-analysis of the TLR data in HIES. Copyright (C) 2008 S. Karger AG, Basel.