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Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study

BACKGROUND: Immunodysregulation polyendocrinopathy enteropathy x-linked(IPEX) syndromeis a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and imm...

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Autores principales: Barzaghi, Federica, Hernandez, Laura Cristina Amaya, Neven, Benedicte, Ricci, Silvia, Kucuk, Zeynep Yesim, Bleesing, Jack J., Nademi, Zohreh, Slatter, Mary Anne, Ulloa, Erlinda Rose, Shcherbina, Anna, Roppelt, Anna, Worth, Austen, Silva, Juliana, Aiuti, Alessandro, Murguia-Favela, Luis, Speckmann, Carsten, Carneiro-Sampaio, Magda, Fernandes, Juliana Folloni, Baris, Safa, Ozen, Ahmet, Karakoc-Aydiner, Elif, Kiykim, Ayca, Schulz, Ansgar, Steinmann, Sandra, Notarangelo, Lucia Dora, Gambineri, Eleonora, Lionetti, Paolo, Shearer, William Thomas, Forbes, Lisa R., Martinez, Caridad, Moshous, Despina, Blanche, Stephane, Fisher, Alain, Ruemmele, Frank M., Tissandier, Come, Ouachee-Chardin, Marie, Rieux-Laucat, Frédéric, Cavazzana, Marina, Qasim, Waseem, Lucarelli, Barbarella, Albert, Michael H., Kobayashi, Ichiro, Alonso, Laura, De Heredia, Cristina Diaz, Kanegane, Hirokazu, Lawitschka, Anita, Seo, Jong Jin, Gonzalez-Vicent, Marta, Diaz, Miguel Angel, Goyal, Rakesh Kumar, Sauer, Martin G., Yesilipek, Akif, Kim, Minsoo, Yilmaz-Demirdag, Yesim, Bhatia, Monica, Khlevner, Julie, Richmond Padilla, Erick J., Martino, Silvana, Montin, Davide, Neth, Olaf, Molinos-Quintana, Agueda, Valverde-Fernandez, Justo, Broides, Arnon, Pinsk, Vered, Ballauf, Antje, Haerynck, Filomeen, Bordon, Victoria, Dhooge, Catharina, Garcia-Lloret, Maria Laura, Bredius, Robbert G., Ka1wak, Krzysztof, Haddad, Elie, Seidel, Markus Gerhard, Duckers, Gregor, Pai, Sung-Yun, Dvorak, Christopher C., Ehl, Stephan, Locatelli, Franco, Goldman, Frederick, Gennery, Andrew Richard, Cowan, Mort J., Roncarolo, Maria-Grazia, Bacchetta, Rosa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050203/
https://www.ncbi.nlm.nih.gov/pubmed/29241729
http://dx.doi.org/10.1016/j.jaci.2017.10.041
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author Barzaghi, Federica
Hernandez, Laura Cristina Amaya
Neven, Benedicte
Ricci, Silvia
Kucuk, Zeynep Yesim
Bleesing, Jack J.
Nademi, Zohreh
Slatter, Mary Anne
Ulloa, Erlinda Rose
Shcherbina, Anna
Roppelt, Anna
Worth, Austen
Silva, Juliana
Aiuti, Alessandro
Murguia-Favela, Luis
Speckmann, Carsten
Carneiro-Sampaio, Magda
Fernandes, Juliana Folloni
Baris, Safa
Ozen, Ahmet
Karakoc-Aydiner, Elif
Kiykim, Ayca
Schulz, Ansgar
Steinmann, Sandra
Notarangelo, Lucia Dora
Gambineri, Eleonora
Lionetti, Paolo
Shearer, William Thomas
Forbes, Lisa R.
Martinez, Caridad
Moshous, Despina
Blanche, Stephane
Fisher, Alain
Ruemmele, Frank M.
Tissandier, Come
Ouachee-Chardin, Marie
Rieux-Laucat, Frédéric
Cavazzana, Marina
Qasim, Waseem
Lucarelli, Barbarella
Albert, Michael H.
Kobayashi, Ichiro
Alonso, Laura
De Heredia, Cristina Diaz
Kanegane, Hirokazu
Lawitschka, Anita
Seo, Jong Jin
Gonzalez-Vicent, Marta
Diaz, Miguel Angel
Goyal, Rakesh Kumar
Sauer, Martin G.
Yesilipek, Akif
Kim, Minsoo
Yilmaz-Demirdag, Yesim
Bhatia, Monica
Khlevner, Julie
Richmond Padilla, Erick J.
Martino, Silvana
Montin, Davide
Neth, Olaf
Molinos-Quintana, Agueda
Valverde-Fernandez, Justo
Broides, Arnon
Pinsk, Vered
Ballauf, Antje
Haerynck, Filomeen
Bordon, Victoria
Dhooge, Catharina
Garcia-Lloret, Maria Laura
Bredius, Robbert G.
Ka1wak, Krzysztof
Haddad, Elie
Seidel, Markus Gerhard
Duckers, Gregor
Pai, Sung-Yun
Dvorak, Christopher C.
Ehl, Stephan
Locatelli, Franco
Goldman, Frederick
Gennery, Andrew Richard
Cowan, Mort J.
Roncarolo, Maria-Grazia
Bacchetta, Rosa
author_facet Barzaghi, Federica
Hernandez, Laura Cristina Amaya
Neven, Benedicte
Ricci, Silvia
Kucuk, Zeynep Yesim
Bleesing, Jack J.
Nademi, Zohreh
Slatter, Mary Anne
Ulloa, Erlinda Rose
Shcherbina, Anna
Roppelt, Anna
Worth, Austen
Silva, Juliana
Aiuti, Alessandro
Murguia-Favela, Luis
Speckmann, Carsten
Carneiro-Sampaio, Magda
Fernandes, Juliana Folloni
Baris, Safa
Ozen, Ahmet
Karakoc-Aydiner, Elif
Kiykim, Ayca
Schulz, Ansgar
Steinmann, Sandra
Notarangelo, Lucia Dora
Gambineri, Eleonora
Lionetti, Paolo
Shearer, William Thomas
Forbes, Lisa R.
Martinez, Caridad
Moshous, Despina
Blanche, Stephane
Fisher, Alain
Ruemmele, Frank M.
Tissandier, Come
Ouachee-Chardin, Marie
Rieux-Laucat, Frédéric
Cavazzana, Marina
Qasim, Waseem
Lucarelli, Barbarella
Albert, Michael H.
Kobayashi, Ichiro
Alonso, Laura
De Heredia, Cristina Diaz
Kanegane, Hirokazu
Lawitschka, Anita
Seo, Jong Jin
Gonzalez-Vicent, Marta
Diaz, Miguel Angel
Goyal, Rakesh Kumar
Sauer, Martin G.
Yesilipek, Akif
Kim, Minsoo
Yilmaz-Demirdag, Yesim
Bhatia, Monica
Khlevner, Julie
Richmond Padilla, Erick J.
Martino, Silvana
Montin, Davide
Neth, Olaf
Molinos-Quintana, Agueda
Valverde-Fernandez, Justo
Broides, Arnon
Pinsk, Vered
Ballauf, Antje
Haerynck, Filomeen
Bordon, Victoria
Dhooge, Catharina
Garcia-Lloret, Maria Laura
Bredius, Robbert G.
Ka1wak, Krzysztof
Haddad, Elie
Seidel, Markus Gerhard
Duckers, Gregor
Pai, Sung-Yun
Dvorak, Christopher C.
Ehl, Stephan
Locatelli, Franco
Goldman, Frederick
Gennery, Andrew Richard
Cowan, Mort J.
Roncarolo, Maria-Grazia
Bacchetta, Rosa
author_sort Barzaghi, Federica
collection PubMed
description BACKGROUND: Immunodysregulation polyendocrinopathy enteropathy x-linked(IPEX) syndromeis a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. OBJECTIVE: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. METHODS: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. RESULTS: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. CONCLUSIONS: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.
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spelling pubmed-60502032018-07-18 Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study Barzaghi, Federica Hernandez, Laura Cristina Amaya Neven, Benedicte Ricci, Silvia Kucuk, Zeynep Yesim Bleesing, Jack J. Nademi, Zohreh Slatter, Mary Anne Ulloa, Erlinda Rose Shcherbina, Anna Roppelt, Anna Worth, Austen Silva, Juliana Aiuti, Alessandro Murguia-Favela, Luis Speckmann, Carsten Carneiro-Sampaio, Magda Fernandes, Juliana Folloni Baris, Safa Ozen, Ahmet Karakoc-Aydiner, Elif Kiykim, Ayca Schulz, Ansgar Steinmann, Sandra Notarangelo, Lucia Dora Gambineri, Eleonora Lionetti, Paolo Shearer, William Thomas Forbes, Lisa R. Martinez, Caridad Moshous, Despina Blanche, Stephane Fisher, Alain Ruemmele, Frank M. Tissandier, Come Ouachee-Chardin, Marie Rieux-Laucat, Frédéric Cavazzana, Marina Qasim, Waseem Lucarelli, Barbarella Albert, Michael H. Kobayashi, Ichiro Alonso, Laura De Heredia, Cristina Diaz Kanegane, Hirokazu Lawitschka, Anita Seo, Jong Jin Gonzalez-Vicent, Marta Diaz, Miguel Angel Goyal, Rakesh Kumar Sauer, Martin G. Yesilipek, Akif Kim, Minsoo Yilmaz-Demirdag, Yesim Bhatia, Monica Khlevner, Julie Richmond Padilla, Erick J. Martino, Silvana Montin, Davide Neth, Olaf Molinos-Quintana, Agueda Valverde-Fernandez, Justo Broides, Arnon Pinsk, Vered Ballauf, Antje Haerynck, Filomeen Bordon, Victoria Dhooge, Catharina Garcia-Lloret, Maria Laura Bredius, Robbert G. Ka1wak, Krzysztof Haddad, Elie Seidel, Markus Gerhard Duckers, Gregor Pai, Sung-Yun Dvorak, Christopher C. Ehl, Stephan Locatelli, Franco Goldman, Frederick Gennery, Andrew Richard Cowan, Mort J. Roncarolo, Maria-Grazia Bacchetta, Rosa J Allergy Clin Immunol Article BACKGROUND: Immunodysregulation polyendocrinopathy enteropathy x-linked(IPEX) syndromeis a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. OBJECTIVE: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. METHODS: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. RESULTS: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. CONCLUSIONS: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen. 2017-12-11 2018-03 /pmc/articles/PMC6050203/ /pubmed/29241729 http://dx.doi.org/10.1016/j.jaci.2017.10.041 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Article
Barzaghi, Federica
Hernandez, Laura Cristina Amaya
Neven, Benedicte
Ricci, Silvia
Kucuk, Zeynep Yesim
Bleesing, Jack J.
Nademi, Zohreh
Slatter, Mary Anne
Ulloa, Erlinda Rose
Shcherbina, Anna
Roppelt, Anna
Worth, Austen
Silva, Juliana
Aiuti, Alessandro
Murguia-Favela, Luis
Speckmann, Carsten
Carneiro-Sampaio, Magda
Fernandes, Juliana Folloni
Baris, Safa
Ozen, Ahmet
Karakoc-Aydiner, Elif
Kiykim, Ayca
Schulz, Ansgar
Steinmann, Sandra
Notarangelo, Lucia Dora
Gambineri, Eleonora
Lionetti, Paolo
Shearer, William Thomas
Forbes, Lisa R.
Martinez, Caridad
Moshous, Despina
Blanche, Stephane
Fisher, Alain
Ruemmele, Frank M.
Tissandier, Come
Ouachee-Chardin, Marie
Rieux-Laucat, Frédéric
Cavazzana, Marina
Qasim, Waseem
Lucarelli, Barbarella
Albert, Michael H.
Kobayashi, Ichiro
Alonso, Laura
De Heredia, Cristina Diaz
Kanegane, Hirokazu
Lawitschka, Anita
Seo, Jong Jin
Gonzalez-Vicent, Marta
Diaz, Miguel Angel
Goyal, Rakesh Kumar
Sauer, Martin G.
Yesilipek, Akif
Kim, Minsoo
Yilmaz-Demirdag, Yesim
Bhatia, Monica
Khlevner, Julie
Richmond Padilla, Erick J.
Martino, Silvana
Montin, Davide
Neth, Olaf
Molinos-Quintana, Agueda
Valverde-Fernandez, Justo
Broides, Arnon
Pinsk, Vered
Ballauf, Antje
Haerynck, Filomeen
Bordon, Victoria
Dhooge, Catharina
Garcia-Lloret, Maria Laura
Bredius, Robbert G.
Ka1wak, Krzysztof
Haddad, Elie
Seidel, Markus Gerhard
Duckers, Gregor
Pai, Sung-Yun
Dvorak, Christopher C.
Ehl, Stephan
Locatelli, Franco
Goldman, Frederick
Gennery, Andrew Richard
Cowan, Mort J.
Roncarolo, Maria-Grazia
Bacchetta, Rosa
Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study
title Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study
title_full Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study
title_fullStr Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study
title_full_unstemmed Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study
title_short Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study
title_sort long-term follow-up of ipex syndrome patients after different therapeutic strategies: an international multicenter retrospective study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050203/
https://www.ncbi.nlm.nih.gov/pubmed/29241729
http://dx.doi.org/10.1016/j.jaci.2017.10.041
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AT roncarolomariagrazia longtermfollowupofipexsyndromepatientsafterdifferenttherapeuticstrategiesaninternationalmulticenterretrospectivestudy
AT bacchettarosa longtermfollowupofipexsyndromepatientsafterdifferenttherapeuticstrategiesaninternationalmulticenterretrospectivestudy