Yazar "Cunningham-Rundles, Charlotte" seçeneğine göre listele

Listeleniyor 1 - 4 / 4
  • Küçük Resim Yok
    Öğe
    Activation-induced cytidine deaminase (AID) is required for B-cell tolerance in humans
    (Natl Acad Sciences, 2011) Meyers, Greta; Ng, Yen-Shing; Bannock, Jason M.; Lavoie, Aubert; Walter, Jolan E.; Notarangelo, Luigi D.; Kilic, Sara S.; Aksu, Guzide; Debre, Marianne; Rieux-Laucat, Frederic; Conley, Mary Ellen; Cunningham-Rundles, Charlotte; Durandy, Anne; Meffre, Eric
    Impaired immune functions leading to primary immunodeficiencies often correlate with paradoxical autoimmune complications; patients with hyper-IgM syndromes who are deficient in activation-induced cytidine deaminase (AID), which is required for classs-witch recombination and somatic hypermutation, are prone to develop autoimmune diseases. To investigate the impact of AID-deficiency on early B-cell tolerance checkpoints in humans, we tested by ELISA the reactivity of recombinant antibodies isolated from single B cells from AID-deficient patients. New emigrant/transitional and mature naive B cells from AID-deficient patients express an abnormal Ig repertoire and high frequencies of autoreactive antibodies, demonstrating that AID is required for the establishment of both central and peripheral B-cell tolerance. In addition, B-cell tolerance was further breached in AID-deficient patients as illustrated by the detection of anti-nuclear IgM antibodies in the serum of all patients. Thus, we identified a major and previously unsuspected role for AID in the removal of developing autoreactive B cells in humans.
  • Küçük Resim Yok
    Öğe
    Granulomatous disease in common variable immunodeficiency
    (Academic Press Inc Elsevier Science, 2009) Ardeniz, Oemuer; Cunningham-Rundles, Charlotte
    Granulomatous disease occurs in 8-22% of patients with common variable immunodeficiency (CVID). We examined the clinical and immunologic information of all 37 of 455 (8.1%) CVID subjects with this complication. The median age at diagnosis of CVID was 26 (2-59). 14 had granulomas 1-18 years before diagnosis of CVID. In 6 detection of granulomas coincided with this diagnosis; for 17, granulomas were documented later. 54% had lung granulomas, 43% in lymph nodes and 32% in liver. 54% of the group had had autoimmune diseases, mostly immune thrombocytopenia and hemolytic anemia. 24% had had a splenectomy. Nineteen (51.3%) required steroid treatment for granulomas; other immune suppressants were used in some. Over 25 years 28.5% died (median age 37.5), but not significantly more when compared to our CVID patients without granulomas (19.8%). Those with lung granulomas had similar mortality to those with granulomas in other tissues. (C) 2009 Elsevier Inc. All rights reserved.
  • Küçük Resim Yok
    Öğe
    Granulomatous disease in common variable immunodeficiency
    (Academic Press Inc Elsevier Science, 2009) Ardeniz, Oemuer; Cunningham-Rundles, Charlotte
    Granulomatous disease occurs in 8-22% of patients with common variable immunodeficiency (CVID). We examined the clinical and immunologic information of all 37 of 455 (8.1%) CVID subjects with this complication. The median age at diagnosis of CVID was 26 (2-59). 14 had granulomas 1-18 years before diagnosis of CVID. In 6 detection of granulomas coincided with this diagnosis; for 17, granulomas were documented later. 54% had lung granulomas, 43% in lymph nodes and 32% in liver. 54% of the group had had autoimmune diseases, mostly immune thrombocytopenia and hemolytic anemia. 24% had had a splenectomy. Nineteen (51.3%) required steroid treatment for granulomas; other immune suppressants were used in some. Over 25 years 28.5% died (median age 37.5), but not significantly more when compared to our CVID patients without granulomas (19.8%). Those with lung granulomas had similar mortality to those with granulomas in other tissues. (C) 2009 Elsevier Inc. All rights reserved.
  • Küçük Resim Yok
    Öğe
    Long-term outcomes of 176 patients with X-linked hyper-IgM syndrome treated with or without hematopoietic cell transplantation
    (Mosby-Elsevier, 2017) de la Morena, M. Teresa; Leonard, David; Torgerson, Troy R.; Cabral-Marques, Otavio; Slatter, Mary; Aghamohammadi, Asghar; Chandra, Sharat; Murguia-Favela, Luis; Bonilla, Francisco A.; Kanariou, Maria; Damrongwatanasuk, Rongras; Kuo, Caroline Y.; Dvorak, Christopher C.; Meyts, Isabelle; Chen, Karin; Kobrynski, Lisa; Kapoor, Neena; Richter, Darko; DiGiovanni, Daniela; Dhalla, Fatima; Farmaki, Evangelia; Speckmann, Carsten; Espanol, Teresa; Shcherbina, Anna; Hanson, Imelda Celine; Litzman, Jiri; Routes, John M.; Wong, Melanie; Fuleihan, Ramsay; Seneviratne, Suranjith L.; Small, Trudy N.; Janda, Ales; Bezrodnik, Liliana; Seger, Reinhard; Raccio, Andrea Gomez; Edgar, J. David M.; Chou, Janet; Abbott, Jordan K.; van Montfrans, Joris; Gonzalez-Granado, Luis Ignacio; Bunin, Nancy; Kutukculer, Necil; Gray, Paul; Seminario, Gisela; Pasic, Srdjan; Aquino, Victor; Wysocki, Christian; Abolhassani, Hassan; Dorsey, Morna; Cunningham-Rundles, Charlotte; Knutsen, Alan P.; Sleasman, John; Carvalho, Beatriz Tavares Costa; Condino-Neto, Antonio; Grunebaum, Eyal; Chapel, Helen; Ochs, Hans D.; Filipovich, Alexandra; Cowan, Mort; Gennery, Andrew; Cant, Andrew; Notarangelo, Luigi D.; Roifman, Chaim M.
    Background: X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency with high morbidity and mortality compared with those seen in healthy subjects. Hematopoietic cell transplantation (HCT) has been considered a curative therapy, but the procedure has inherent complications and might not be available for all patients. Objectives: We sought to collect data on the clinical presentation, treatment, and follow-up of a large sample of patients with XHIGM to (1) compare long-term overall survival and general well-being of patients treated with or without HCT along with clinical factors associated with mortality and (2) summarize clinical practice and risk factors in the subgroup of patients treated with HCT. Methods: Physicians caring for patients with primary immunodeficiency diseases were identified through the Jeffrey Modell Foundation, United States Immunodeficiency Network, Latin American Society for Immunodeficiency, and Primary Immune Deficiency Treatment Consortium. Data were collected with a Research Electronic Data Capture Web application. Survival from time of diagnosis or transplantation was estimated by using the Kaplan-Meier method compared with log-rank tests and modeled by using proportional hazards regression. Results: Twenty-eight clinical sites provided data on 189 patients given a diagnosis of XHIGM between 1964 and 2013; 176 had valid follow-up and vital status information. Sixty-seven (38%) patients received HCT. The average follow-up time was 8.5 +/- 7.2 years (range, 0.1-36.2 years). No difference in overall survival was observed between patients treated with or without HCT (P = .671). However, risk associated with HCT decreased for diagnosis years 1987-1995; the hazard ratio was significantly less than 1 for diagnosis years 1995-1999. Liver disease was a significant predictor of overall survival (hazard ratio, 4.9; 95% confidence limits, 2.2-10.8; P < .001). Among survivors, those treated with HCT had higher median Karnofsky/Lansky scores than those treated without HCT (P < .001). Among patients receiving HCT, 27 (40%) had graft-versus-host disease, and most deaths occurred within 1 year of transplantation. Conclusion: No difference in survival was observed between patients treated with or without HCT across all diagnosis years (1964-2013). However, survivors treated with HCT experienced somewhat greater well-being, and hazards associated with HCT decreased, reaching levels of significantly less risk in the late 1990s. Among patients treated with HCT, treatment at an early age is associated with improved survival. Optimism remains guarded as additional evidence accumulates.