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1. Adolescent gender dysphoria management: position paper from the Italian Academy of Pediatrics, the Italian Society of Pediatrics, the Italian Society for Pediatric Endocrinology and Diabetes, the Italian Society of Adolescent Medicine and the Italian Society of Child and Adolescent Neuropsychiatry

Author

Calcaterra, V, Tornese, G, Zuccotti, G, Staiano, A, Cherubini, V, Gaudino, R, Fazzi, E, Barbi, E, Chiarelli, F, Corsello, G, Esposito, S, Ferrara, P, Iughetti, L, Laforgia, N, Maghnie, M, Marseglia, G, Perilongo, G, Pettoello-Mantovani, M, Ruggieri, M, Russo, G, Salerno, M, Striano, P, Valerio, G, Wasniewska, M, Agosti, M, Agostoni, C, Aiuti, A, Azzari, C, Badolato, R, Balduzzi, A, Baraldi, E, Canani, R, Biffi, A, Biondi, A, Bisogno, G, Pierri, N, Carnielli, V, Cianfarani, S, Cogo, P, Corvaglia, L, Dani, C, Di Salvo, G, Fagioli, F, Fanos, V, Ferrero, G, Francavilla, R, Galli, L, Gazzolo, D, Giaquinto, C, Giordano, P, Gitto, E, Grosso, S, Guarino, A, Indrio, F, Lanari, M, Lionetti, P, Locatelli, F, Lombardo, F, Maffeis, C, Marino, B, Midulla, F, Del Giudice, E, Del Giudice, M, Montini, G, Parenti, G, Parisi, P, Peroni, D, Perrotta, S, Piacentini, G, Pietrobelli, A, Raimondi, F, Ramenghi, U, Ravelli, A, Romano, C, Rossi, F, Rossi, P, Damiano, V, Spalice, A, Suppiej, A, Troncone, R, Verrotti, A, Null, N, Calcaterra, Valeria, Tornese, Gianluca, Zuccotti, Gianvincenzo, Staiano, Annamaria, Cherubini, Valentino, Gaudino, Rossella, Fazzi, Elisa Maria, Barbi, Egidio, Chiarelli, Francesco, Corsello, Giovanni, Esposito, Susanna Maria Roberta, Ferrara, Pietro, Iughetti, Lorenzo, Laforgia, Nicola, Maghnie, Mohamad, Marseglia, Gianluigi, Perilongo, Giorgio, Pettoello-Mantovani, Massimo, Ruggieri, Martino, Russo, Giovanna, Salerno, Mariacarolina, Striano, Pasquale, Valerio, Giuliana, Wasniewska, Malgorzata, Agosti, Massimo, Agostoni, Carlo Virginio, Aiuti, Alessandro, Azzari, Chiara, Badolato, Raffaele, Balduzzi, Adriana, Baraldi, Eugenio, Canani, Roberto Berni, Biffi, Alessandra, Biondi, Andrea, Bisogno, Gianni, Pierri, Nicola Brunetti, Carnielli, Virginio, Cianfarani, Stefano, Cogo, Paola, Corvaglia, Luigi, Dani, Carlo, Di Salvo, Giovanni, Fagioli, Franca, Fanos, Vassilios, Ferrero, Giovanni Battista, Francavilla, Ruggiero, Galli, Luisa, Gazzolo, Diego, Giaquinto, Carlo, Giordano, Paola, Gitto, Eloisa, Grosso, Salvatore, Guarino, Alfredo, Indrio, Flavia, Lanari, Marcello, Lionetti, Paolo, Locatelli, Franco, Lombardo, Fortunato, Maffeis, Claudio, Marino, Bruno, Midulla, Fabio, Del Giudice, Emanuele Miraglia, Del Giudice, Michele Miraglia, Montini, Giovanni, Parenti, Giancarlo, Parisi, Pasquale, Peroni, Diego, Perrotta, Silverio, Piacentini, Giorgio, Pietrobelli, Angelo, Raimondi, Francesco, Ramenghi, Ugo, Ravelli, Angelo, Romano, Claudio, Rossi, Francesca, Rossi, Paolo, Damiano, Vincenzo Salpietro, Spalice, Alberto, Suppiej, Agnese, Troncone, Riccardo, Verrotti, Alberto, null, null, Calcaterra, V, Tornese, G, Zuccotti, G, Staiano, A, Cherubini, V, Gaudino, R, Fazzi, E, Barbi, E, Chiarelli, F, Corsello, G, Esposito, S, Ferrara, P, Iughetti, L, Laforgia, N, Maghnie, M, Marseglia, G, Perilongo, G, Pettoello-Mantovani, M, Ruggieri, M, Russo, G, Salerno, M, Striano, P, Valerio, G, Wasniewska, M, Agosti, M, Agostoni, C, Aiuti, A, Azzari, C, Badolato, R, Balduzzi, A, Baraldi, E, Canani, R, Biffi, A, Biondi, A, Bisogno, G, Pierri, N, Carnielli, V, Cianfarani, S, Cogo, P, Corvaglia, L, Dani, C, Di Salvo, G, Fagioli, F, Fanos, V, Ferrero, G, Francavilla, R, Galli, L, Gazzolo, D, Giaquinto, C, Giordano, P, Gitto, E, Grosso, S, Guarino, A, Indrio, F, Lanari, M, Lionetti, P, Locatelli, F, Lombardo, F, Maffeis, C, Marino, B, Midulla, F, Del Giudice, E, Del Giudice, M, Montini, G, Parenti, G, Parisi, P, Peroni, D, Perrotta, S, Piacentini, G, Pietrobelli, A, Raimondi, F, Ramenghi, U, Ravelli, A, Romano, C, Rossi, F, Rossi, P, Damiano, V, Spalice, A, Suppiej, A, Troncone, R, Verrotti, A, Null, N, Calcaterra, Valeria, Tornese, Gianluca, Zuccotti, Gianvincenzo, Staiano, Annamaria, Cherubini, Valentino, Gaudino, Rossella, Fazzi, Elisa Maria, Barbi, Egidio, Chiarelli, Francesco, Corsello, Giovanni, Esposito, Susanna Maria Roberta, Ferrara, Pietro, Iughetti, Lorenzo, Laforgia, Nicola, Maghnie, Mohamad, Marseglia, Gianluigi, Perilongo, Giorgio, Pettoello-Mantovani, Massimo, Ruggieri, Martino, Russo, Giovanna, Salerno, Mariacarolina, Striano, Pasquale, Valerio, Giuliana, Wasniewska, Malgorzata, Agosti, Massimo, Agostoni, Carlo Virginio, Aiuti, Alessandro, Azzari, Chiara, Badolato, Raffaele, Balduzzi, Adriana, Baraldi, Eugenio, Canani, Roberto Berni, Biffi, Alessandra, Biondi, Andrea, Bisogno, Gianni, Pierri, Nicola Brunetti, Carnielli, Virginio, Cianfarani, Stefano, Cogo, Paola, Corvaglia, Luigi, Dani, Carlo, Di Salvo, Giovanni, Fagioli, Franca, Fanos, Vassilios, Ferrero, Giovanni Battista, Francavilla, Ruggiero, Galli, Luisa, Gazzolo, Diego, Giaquinto, Carlo, Giordano, Paola, Gitto, Eloisa, Grosso, Salvatore, Guarino, Alfredo, Indrio, Flavia, Lanari, Marcello, Lionetti, Paolo, Locatelli, Franco, Lombardo, Fortunato, Maffeis, Claudio, Marino, Bruno, Midulla, Fabio, Del Giudice, Emanuele Miraglia, Del Giudice, Michele Miraglia, Montini, Giovanni, Parenti, Giancarlo, Parisi, Pasquale, Peroni, Diego, Perrotta, Silverio, Piacentini, Giorgio, Pietrobelli, Angelo, Raimondi, Francesco, Ramenghi, Ugo, Ravelli, Angelo, Romano, Claudio, Rossi, Francesca, Rossi, Paolo, Damiano, Vincenzo Salpietro, Spalice, Alberto, Suppiej, Agnese, Troncone, Riccardo, Verrotti, Alberto, and null, null

Abstract

Background In response to the imperative need for standardized support for adolescent Gender Dysphoria (GD), the Italian Academy of Pediatrics, in collaboration with the Italian Society of Pediatrics, the Italian Society for Pediatric Endocrinology and Diabetes, Italian Society of Adolescent Medicine and Italian Society of Child and Adolescent Neuropsychiatry is drafting a position paper. The purpose of this paper is to convey the author's opinion on the topic, offering foundational information on potential aspects of gender-affirming care and emphasizing the care and protection of children and adolescents with GD.Main body Recognizing that adolescents may choose interventions based on their unique needs and goals and understanding that every individual within this group has a distinct trajectory, it is crucial to ensure that each one is welcomed and supported. The approach to managing individuals with GD is a multi-stage process involving a multidisciplinary team throughout all phases. Decisions regarding treatment should be reached collaboratively by healthcare professionals and the family, while considering the unique needs and circumstances of the individual and be guided by scientific evidence rather than biases or ideologies. Politicians and high court judges should address discrimination based on gender identity in legislation and support service development that aligns with the needs of young people. It is essential to establish accredited multidisciplinary centers equipped with the requisite skills and experience to effectively manage adolescents with GD, thereby ensuring the delivery of high-quality care.Conclusion Maintaining an evidence-based approach is essential to safeguard the well-being of transgender and gender diverse adolescents.

Published
2024

2. Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C.

Author

Burbelo, Peter D, Burbelo, Peter D, Castagnoli, Riccardo, Shimizu, Chisato, Delmonte, Ottavia M, Dobbs, Kerry, Discepolo, Valentina, Lo Vecchio, Andrea, Guarino, Alfredo, Licciardi, Francesco, Ramenghi, Ugo, Rey-Jurado, Emma, Vial, Cecilia, Marseglia, Gian Luigi, Licari, Amelia, Montagna, Daniela, Rossi, Camillo, Montealegre Sanchez, Gina A, Barron, Karyl, Warner, Blake M, Chiorini, John A, Espinosa, Yazmin, Noguera, Loreani, Dropulic, Lesia, Truong, Meng, Gerstbacher, Dana, Mató, Sayonara, Kanegaye, John, Tremoulet, Adriana H, Pediatric Emergency Medicine Kawasaki Group, Eisenstein, Eli M, Su, Helen C, Imberti, Luisa, Poli, Maria Cecilia, Burns, Jane C, Notarangelo, Luigi D, Cohen, Jeffrey I, Burbelo, Peter D, Burbelo, Peter D, Castagnoli, Riccardo, Shimizu, Chisato, Delmonte, Ottavia M, Dobbs, Kerry, Discepolo, Valentina, Lo Vecchio, Andrea, Guarino, Alfredo, Licciardi, Francesco, Ramenghi, Ugo, Rey-Jurado, Emma, Vial, Cecilia, Marseglia, Gian Luigi, Licari, Amelia, Montagna, Daniela, Rossi, Camillo, Montealegre Sanchez, Gina A, Barron, Karyl, Warner, Blake M, Chiorini, John A, Espinosa, Yazmin, Noguera, Loreani, Dropulic, Lesia, Truong, Meng, Gerstbacher, Dana, Mató, Sayonara, Kanegaye, John, Tremoulet, Adriana H, Pediatric Emergency Medicine Kawasaki Group, Eisenstein, Eli M, Su, Helen C, Imberti, Luisa, Poli, Maria Cecilia, Burns, Jane C, Notarangelo, Luigi D, and Cohen, Jeffrey I

Abstract

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren's syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

Published
2022

3. Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C.

Author

Burbelo, Peter D, Burbelo, Peter D, Castagnoli, Riccardo, Shimizu, Chisato, Delmonte, Ottavia M, Dobbs, Kerry, Discepolo, Valentina, Lo Vecchio, Andrea, Guarino, Alfredo, Licciardi, Francesco, Ramenghi, Ugo, Rey-Jurado, Emma, Vial, Cecilia, Marseglia, Gian Luigi, Licari, Amelia, Montagna, Daniela, Rossi, Camillo, Montealegre Sanchez, Gina A, Barron, Karyl, Warner, Blake M, Chiorini, John A, Espinosa, Yazmin, Noguera, Loreani, Dropulic, Lesia, Truong, Meng, Gerstbacher, Dana, Mató, Sayonara, Kanegaye, John, Tremoulet, Adriana H, Pediatric Emergency Medicine Kawasaki Group, Eisenstein, Eli M, Su, Helen C, Imberti, Luisa, Poli, Maria Cecilia, Burns, Jane C, Notarangelo, Luigi D, Cohen, Jeffrey I, Burbelo, Peter D, Burbelo, Peter D, Castagnoli, Riccardo, Shimizu, Chisato, Delmonte, Ottavia M, Dobbs, Kerry, Discepolo, Valentina, Lo Vecchio, Andrea, Guarino, Alfredo, Licciardi, Francesco, Ramenghi, Ugo, Rey-Jurado, Emma, Vial, Cecilia, Marseglia, Gian Luigi, Licari, Amelia, Montagna, Daniela, Rossi, Camillo, Montealegre Sanchez, Gina A, Barron, Karyl, Warner, Blake M, Chiorini, John A, Espinosa, Yazmin, Noguera, Loreani, Dropulic, Lesia, Truong, Meng, Gerstbacher, Dana, Mató, Sayonara, Kanegaye, John, Tremoulet, Adriana H, Pediatric Emergency Medicine Kawasaki Group, Eisenstein, Eli M, Su, Helen C, Imberti, Luisa, Poli, Maria Cecilia, Burns, Jane C, Notarangelo, Luigi D, and Cohen, Jeffrey I

Abstract

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren's syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

Published
2022

4. Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19

Author

Carmona-Rivera, C, Zhang, Y, Dobbs, K, Markowitz, T, Dalgard, C, Oler, A, Claybaugh, D, Draper, D, Truong, M, Delmonte, O, Licciardi, F, Ramenghi, U, Crescenzio, N, Imberti, L, Sottini, A, Quaresima, V, Fiorini, C, Discepolo, V, Lo Vecchio, A, Guarino, A, Pierri, L, Catzola, A, Biondi, A, Bonfanti, P, Poli Harlowe, M, Espinosa, Y, Astudillo, C, Rey-Jurado, E, Vial, C, De la Cruz, J, Gonzalez, R, Pinera, C, Mays, J, Ng, A, Platt, A, Drolet, B, Moon, J, Cowen, E, Kenney, H, Weber, S, Castagnoli, R, Magliocco, M, Stack, M, Montealegre Sanchez, G, Barron, K, Fink, D, Kuhns, D, Hewitt, S, Arkin, L, Chertow, D, Su, H, Notarangelo, L, Kaplan, M, Carmona-Rivera, Carmelo, Zhang, Yu, Dobbs, Kerry, Markowitz, Tovah E, Dalgard, Clifton L, Oler, Andrew J, Claybaugh, Dillon R, Draper, Deborah, Truong, Meng, Delmonte, Ottavia M, Licciardi, Francesco, Ramenghi, Ugo, Crescenzio, Nicoletta, Imberti, Luisa, Sottini, Alessandra, Quaresima, Virginia, Fiorini, Chiara, Discepolo, Valentina, Lo Vecchio, Andrea, Guarino, Alfredo, Pierri, Luca, Catzola, Andrea, Biondi, Andrea, Bonfanti, Paolo, Poli Harlowe, Maria Cecilia, Espinosa, Yazmin, Astudillo, Camila A, Rey-Jurado, Emma, Vial, Cecilia, De la Cruz, Javiera, Gonzalez, Ricardo, Pinera, Cecilia, Mays, Jacqueline W, Ng, Ashley, Platt, Andrew, Drolet, Beth A, Moon, John, Cowen, Edward W, Kenney, Heather, Weber, Sarah E, Castagnoli, Riccardo, Magliocco, Mary K, Stack, Michael Austin, Montealegre Sanchez, Gina A, Barron, Karyl, Fink, Danielle L, Kuhns, Douglas B, Hewitt, Stephen M, Arkin, Lisa M, Chertow, Daniel S, Su, Helen C, Notarangelo, Luigi D, Kaplan, Mariana J, Carmona-Rivera, C, Zhang, Y, Dobbs, K, Markowitz, T, Dalgard, C, Oler, A, Claybaugh, D, Draper, D, Truong, M, Delmonte, O, Licciardi, F, Ramenghi, U, Crescenzio, N, Imberti, L, Sottini, A, Quaresima, V, Fiorini, C, Discepolo, V, Lo Vecchio, A, Guarino, A, Pierri, L, Catzola, A, Biondi, A, Bonfanti, P, Poli Harlowe, M, Espinosa, Y, Astudillo, C, Rey-Jurado, E, Vial, C, De la Cruz, J, Gonzalez, R, Pinera, C, Mays, J, Ng, A, Platt, A, Drolet, B, Moon, J, Cowen, E, Kenney, H, Weber, S, Castagnoli, R, Magliocco, M, Stack, M, Montealegre Sanchez, G, Barron, K, Fink, D, Kuhns, D, Hewitt, S, Arkin, L, Chertow, D, Su, H, Notarangelo, L, Kaplan, M, Carmona-Rivera, Carmelo, Zhang, Yu, Dobbs, Kerry, Markowitz, Tovah E, Dalgard, Clifton L, Oler, Andrew J, Claybaugh, Dillon R, Draper, Deborah, Truong, Meng, Delmonte, Ottavia M, Licciardi, Francesco, Ramenghi, Ugo, Crescenzio, Nicoletta, Imberti, Luisa, Sottini, Alessandra, Quaresima, Virginia, Fiorini, Chiara, Discepolo, Valentina, Lo Vecchio, Andrea, Guarino, Alfredo, Pierri, Luca, Catzola, Andrea, Biondi, Andrea, Bonfanti, Paolo, Poli Harlowe, Maria Cecilia, Espinosa, Yazmin, Astudillo, Camila A, Rey-Jurado, Emma, Vial, Cecilia, De la Cruz, Javiera, Gonzalez, Ricardo, Pinera, Cecilia, Mays, Jacqueline W, Ng, Ashley, Platt, Andrew, Drolet, Beth A, Moon, John, Cowen, Edward W, Kenney, Heather, Weber, Sarah E, Castagnoli, Riccardo, Magliocco, Mary K, Stack, Michael Austin, Montealegre Sanchez, Gina A, Barron, Karyl, Fink, Danielle L, Kuhns, Douglas B, Hewitt, Stephen M, Arkin, Lisa M, Chertow, Daniel S, Su, Helen C, Notarangelo, Luigi D, and Kaplan, Mariana J

Abstract

Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease, including multisystem inflammatory syndrome in children (MIS-C) and chilblain-like lesions (CLLs), otherwise known as "COVID toes,"remains unclear. Studying multinational cohorts, we found that, in CLLs, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs after disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased NET levels when compared with other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.

Published
2022

5. Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19

Author

Sacco, K, Castagnoli, R, Vakkilainen, S, Liu, C, Delmonte, O, Oguz, C, Kaplan, I, Alehashemi, S, Burbelo, P, Bhuyan, F, de Jesus, A, Dobbs, K, Rosen, L, Cheng, A, Shaw, E, Vakkilainen, M, Pala, F, Lack, J, Zhang, Y, Fink, D, Oikonomou, V, Snow, A, Dalgard, C, Chen, J, Sellers, B, Montealegre Sanchez, G, Barron, K, Rey-Jurado, E, Vial, C, Poli, M, Licari, A, Montagna, D, Marseglia, G, Licciardi, F, Ramenghi, U, Discepolo, V, Lo Vecchio, A, Guarino, A, Eisenstein, E, Imberti, L, Sottini, A, Biondi, A, Mató, S, Gerstbacher, D, Truong, M, Stack, M, Magliocco, M, Bosticardo, M, Kawai, T, Danielson, J, Hulett, T, Askenazi, M, Hu, S, Cohen, J, Su, H, Kuhns, D, Lionakis, M, Snyder, T, Holland, S, Goldbach-Mansky, R, Tsang, J, Notarangelo, L, Sacco, Keith, Castagnoli, Riccardo, Vakkilainen, Svetlana, Liu, Can, Delmonte, Ottavia M, Oguz, Cihan, Kaplan, Ian M, Alehashemi, Sara, Burbelo, Peter D, Bhuyan, Farzana, de Jesus, Adriana A, Dobbs, Kerry, Rosen, Lindsey B, Cheng, Aristine, Shaw, Elana, Vakkilainen, Mikko S, Pala, Francesca, Lack, Justin, Zhang, Yu, Fink, Danielle L, Oikonomou, Vasileios, Snow, Andrew L, Dalgard, Clifton L, Chen, Jinguo, Sellers, Brian A, Montealegre Sanchez, Gina A, Barron, Karyl, Rey-Jurado, Emma, Vial, Cecilia, Poli, Maria Cecilia, Licari, Amelia, Montagna, Daniela, Marseglia, Gian Luigi, Licciardi, Francesco, Ramenghi, Ugo, Discepolo, Valentina, Lo Vecchio, Andrea, Guarino, Alfredo, Eisenstein, Eli M, Imberti, Luisa, Sottini, Alessandra, Biondi, Andrea, Mató, Sayonara, Gerstbacher, Dana, Truong, Meng, Stack, Michael A, Magliocco, Mary, Bosticardo, Marita, Kawai, Tomoki, Danielson, Jeffrey J, Hulett, Tyler, Askenazi, Manor, Hu, Shaohui, Cohen, Jeffrey I, Su, Helen C, Kuhns, Douglas B, Lionakis, Michail S, Snyder, Thomas M, Holland, Steven M, Goldbach-Mansky, Raphaela, Tsang, John S, Notarangelo, Luigi D, Sacco, K, Castagnoli, R, Vakkilainen, S, Liu, C, Delmonte, O, Oguz, C, Kaplan, I, Alehashemi, S, Burbelo, P, Bhuyan, F, de Jesus, A, Dobbs, K, Rosen, L, Cheng, A, Shaw, E, Vakkilainen, M, Pala, F, Lack, J, Zhang, Y, Fink, D, Oikonomou, V, Snow, A, Dalgard, C, Chen, J, Sellers, B, Montealegre Sanchez, G, Barron, K, Rey-Jurado, E, Vial, C, Poli, M, Licari, A, Montagna, D, Marseglia, G, Licciardi, F, Ramenghi, U, Discepolo, V, Lo Vecchio, A, Guarino, A, Eisenstein, E, Imberti, L, Sottini, A, Biondi, A, Mató, S, Gerstbacher, D, Truong, M, Stack, M, Magliocco, M, Bosticardo, M, Kawai, T, Danielson, J, Hulett, T, Askenazi, M, Hu, S, Cohen, J, Su, H, Kuhns, D, Lionakis, M, Snyder, T, Holland, S, Goldbach-Mansky, R, Tsang, J, Notarangelo, L, Sacco, Keith, Castagnoli, Riccardo, Vakkilainen, Svetlana, Liu, Can, Delmonte, Ottavia M, Oguz, Cihan, Kaplan, Ian M, Alehashemi, Sara, Burbelo, Peter D, Bhuyan, Farzana, de Jesus, Adriana A, Dobbs, Kerry, Rosen, Lindsey B, Cheng, Aristine, Shaw, Elana, Vakkilainen, Mikko S, Pala, Francesca, Lack, Justin, Zhang, Yu, Fink, Danielle L, Oikonomou, Vasileios, Snow, Andrew L, Dalgard, Clifton L, Chen, Jinguo, Sellers, Brian A, Montealegre Sanchez, Gina A, Barron, Karyl, Rey-Jurado, Emma, Vial, Cecilia, Poli, Maria Cecilia, Licari, Amelia, Montagna, Daniela, Marseglia, Gian Luigi, Licciardi, Francesco, Ramenghi, Ugo, Discepolo, Valentina, Lo Vecchio, Andrea, Guarino, Alfredo, Eisenstein, Eli M, Imberti, Luisa, Sottini, Alessandra, Biondi, Andrea, Mató, Sayonara, Gerstbacher, Dana, Truong, Meng, Stack, Michael A, Magliocco, Mary, Bosticardo, Marita, Kawai, Tomoki, Danielson, Jeffrey J, Hulett, Tyler, Askenazi, Manor, Hu, Shaohui, Cohen, Jeffrey I, Su, Helen C, Kuhns, Douglas B, Lionakis, Michail S, Snyder, Thomas M, Holland, Steven M, Goldbach-Mansky, Raphaela, Tsang, John S, and Notarangelo, Luigi D

Abstract

Transcriptomic, proteomic and immune repertoire profiling reveals distinct peripheral features of MIS-C and pediatric COVID-19, including elevated soluble spike protein levels, more pronounced type II IFN-dependent gene expression and a higher B cell mutation rate in patients with MIS-C.Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-kappa B-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy.

Published
2022

6. Molecular approaches to diagnose Diamond-Blackfan anemia : The EuroDBA experience

Author

Da Costa, Lydie, O'Donohue, Marie Françoise, van Dooijeweert, Birgit, Albrecht, Katarzyna, Unal, Sule, Ramenghi, Ugo, Leblanc, Thierry, Dianzani, Irma, Tamary, Hannah, Bartels, Marije, Gleizes, Pierre Emmanuel, Wlodarski, Marcin W., MacInnes, Alyson W., Da Costa, Lydie, O'Donohue, Marie Françoise, van Dooijeweert, Birgit, Albrecht, Katarzyna, Unal, Sule, Ramenghi, Ugo, Leblanc, Thierry, Dianzani, Irma, Tamary, Hannah, Bartels, Marije, Gleizes, Pierre Emmanuel, Wlodarski, Marcin W., and MacInnes, Alyson W.

Published
2018

7. Molecular approaches to diagnose Diamond-Blackfan anemia : The EuroDBA experience

Author

Da Costa, Lydie, O'Donohue, Marie Françoise, van Dooijeweert, Birgit, Albrecht, Katarzyna, Unal, Sule, Ramenghi, Ugo, Leblanc, Thierry, Dianzani, Irma, Tamary, Hannah, Bartels, Marije, Gleizes, Pierre Emmanuel, Wlodarski, Marcin W., MacInnes, Alyson W., Da Costa, Lydie, O'Donohue, Marie Françoise, van Dooijeweert, Birgit, Albrecht, Katarzyna, Unal, Sule, Ramenghi, Ugo, Leblanc, Thierry, Dianzani, Irma, Tamary, Hannah, Bartels, Marije, Gleizes, Pierre Emmanuel, Wlodarski, Marcin W., and MacInnes, Alyson W.

Published
2018

8. Molecular approaches to diagnose Diamond-Blackfan anemia : The EuroDBA experience

Author

Da Costa, Lydie, O'Donohue, Marie Françoise, van Dooijeweert, Birgit, Albrecht, Katarzyna, Unal, Sule, Ramenghi, Ugo, Leblanc, Thierry, Dianzani, Irma, Tamary, Hannah, Bartels, Marije, Gleizes, Pierre Emmanuel, Wlodarski, Marcin W., MacInnes, Alyson W., Da Costa, Lydie, O'Donohue, Marie Françoise, van Dooijeweert, Birgit, Albrecht, Katarzyna, Unal, Sule, Ramenghi, Ugo, Leblanc, Thierry, Dianzani, Irma, Tamary, Hannah, Bartels, Marije, Gleizes, Pierre Emmanuel, Wlodarski, Marcin W., and MacInnes, Alyson W.

Published
2018

9. Haematopoietic stem cell transplantation for Diamond Blackfan anaemia: a report from the Italian Association of Paediatric Haematology and Oncology Registry

Author

Fagioli, Franca, Quarello, Paola, Zecca, Marco, Lanino, Edoardo, Corti, Paola, Favre, Claudio, Ripaldi, Mimmo, Ramenghi, Ugo, Locatelli, Franco, Prete, Arcangelo, Locatelli, Franco (ORCID:0000-0002-7976-3654), Fagioli, Franca, Quarello, Paola, Zecca, Marco, Lanino, Edoardo, Corti, Paola, Favre, Claudio, Ripaldi, Mimmo, Ramenghi, Ugo, Locatelli, Franco, Prete, Arcangelo, and Locatelli, Franco (ORCID:0000-0002-7976-3654)

Abstract

Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative option for patients with Diamond Blackfan anaemia (DBA). We report the transplantation outcome of 30 Italian DBA patients referred to the Italian Association of Paediatric Haematology and Oncology Registry between 1990 and 2012. This is one of the largest national registry cohorts of transplanted DBA patients. Most patients (83%) were allografted after 2000. A matched sibling donor was employed in 16 patients (53%), the remaining 14 patients (47%) were transplanted from matched unrelated donors. Twenty-eight of the 30 patients engrafted. One patient died at day +6 due to veno-occlusive disease without achieving neutrophil recovery and another patient remained transfusion-dependent despite the presence of a full donor chimerism. The 5-year overall survival and transplant-related mortality was 744% and 256%, respectively. Patients younger than 10years as well as those transplanted after 2000 showed a significantly higher overall survival and a significantly lower risk of transplant-related mortality. No difference between donor type was observed. Our data suggest that allogeneic HSCT from a related or unrelated donor was a reasonable alternative to transfusion therapy in young and well chelated DBA patients.

Published
2014

10. Paroxysmal nocturnal hemoglobinuria clones in children with acquired aplastic anemia: A multicentre study

Author

Timeus, Fabio, Crescenzio, Nicoletta, Longoni, Daniela, Doria, Alessandra, Foglia, Luiselda, Pagliano, Sara, Vallero, Stefano, Decimi, Valentina, Svahn, Johanna, Palumbo, Giuseppe, Ruggiero, Antonio, Martire, Baldassarre, Pillon, Marta, Marra, Nicoletta, Dufour, Carlo, Ramenghi, Ugo, Saracco, Paola, Ruggiero, Antonio (ORCID:0000-0002-6052-3511), Timeus, Fabio, Crescenzio, Nicoletta, Longoni, Daniela, Doria, Alessandra, Foglia, Luiselda, Pagliano, Sara, Vallero, Stefano, Decimi, Valentina, Svahn, Johanna, Palumbo, Giuseppe, Ruggiero, Antonio, Martire, Baldassarre, Pillon, Marta, Marra, Nicoletta, Dufour, Carlo, Ramenghi, Ugo, Saracco, Paola, and Ruggiero, Antonio (ORCID:0000-0002-6052-3511)

Abstract

A multicentre study evaluating the presence of glycosil phosphatidyl-inositol (GPI)-negative populations was performed in 85 children with acquired aplastic anemia (AA). A GPI-negative population was observed in 41% of patients at diagnosis, 48% during immune-suppressive therapy (IST), and 45% in patients off-therapy. No association was found between the presence of a GPI-negative population at diagnosis and the response to IST. In addition, the response rate to IST did not differ between the patients who were GPI-positive at diagnosis and later developed GPI-negative populations and the 11 patients who remained GPI-positive. Two patients with a GPI-negative population >10%, and laboratory signs of hemolysis without hemoglobinuria were considered affected by paroxysmal nocturnal hemoglobinuria (PNH) secondary to AA; no thrombotic event was reported. Excluding the 2 patients with a GPI-negative population greater than 10%, we did not observe a significant correlation between LDH levels and GPI-negative population size. In this study monitoring for laboratory signs of hemolysis was sufficient to diagnose PNH in AA patients. The presence of minor GPI-negative populations at diagnosis in our series did not influence the therapeutic response. As occasionally the appearance of a GPI-negative population was observed at cyclosporine (CSA) tapering or AA relapse, a possible role of GPI-negative population monitoring during IST modulation may need further investigation. © 2014 Timeus et al.

Published
2014

11. The ribosomal basis of Diamond-Blackfan Anemia : mutation and database update

Author

Boria, Ilenia, Garelli, Emanuela, Gazda, Hanna T., Aspesi, Anna, Quarello, Paola, Pavesi, Elisa, Ferrante, Daniela, Meerpohl, Joerg J., Kartal, Mutlu, Da Costa, Lydie, Proust, Alexis, Leblanc, Thierry, Simansour, Maud, Dahl, Niklas, Fröjmark, Anne-Sophie, Pospisilova, Dagmar, Cmejla, Radek, Beggs, Alan H., Sheen, Mee R., Landowski, Michael, Buros, Christopher M., Clinton, Catherine M., Dobson, Lori J., Vlachos, Adrianna, Atsidaftos, Eva, Lipton, Jeffrey M., Ellis, Steven R., Ramenghi, Ugo, Dianzani, Irma, Boria, Ilenia, Garelli, Emanuela, Gazda, Hanna T., Aspesi, Anna, Quarello, Paola, Pavesi, Elisa, Ferrante, Daniela, Meerpohl, Joerg J., Kartal, Mutlu, Da Costa, Lydie, Proust, Alexis, Leblanc, Thierry, Simansour, Maud, Dahl, Niklas, Fröjmark, Anne-Sophie, Pospisilova, Dagmar, Cmejla, Radek, Beggs, Alan H., Sheen, Mee R., Landowski, Michael, Buros, Christopher M., Clinton, Catherine M., Dobson, Lori J., Vlachos, Adrianna, Atsidaftos, Eva, Lipton, Jeffrey M., Ellis, Steven R., Ramenghi, Ugo, and Dianzani, Irma

Abstract

Diamond-Blackfan Anemia (DBA) is characterized by a defect of erythroid progenitors and, clinically, by anemia and malformations. DBA exhibits an autosomal dominant pattern of inheritance with incomplete penetrance. Currently nine genes, all encoding ribosomal proteins (RP), have been found mutated in approximately 50% of patients. Experimental evidence supports the hypothesis that DBA is primarily the result of defective ribosome synthesis. By means of a large collaboration among six centers, we report here a mutation update that includes nine genes and 220 distinct mutations, 56 of which are new. The DBA Mutation Database now includes data from 355 patients. Of those where inheritance has been examined, 125 patients carry a de novo mutation and 72 an inherited mutation. Mutagenesis may be ascribed to slippage in 65.5% of indels, whereas CpG dinucleotides are involved in 23% of transitions. Using bioinformatic tools we show that gene conversion mechanism is not common in RP genes mutagenesis, notwithstanding the abundance of RP pseudogenes. Genotype-phenotype analysis reveals that malformations are more frequently associated with mutations in RPL5 and RPL11 than in the other genes. All currently reported DBA mutations together with their functional and clinical data are included in the DBA Mutation Database.

Published
2010
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12. Diagnosing and treating Diamond Blackfan anaemia : results of an international clinical consensus conference

Author

Vlachos, Adrianna, Ball, Sarah, Dahl, Niklas, Alter, Blanche P., Sheth, Sujit, Ramenghi, Ugo, Meerpohl, Joerg, Karlsson, Stefan, Liu, Johnson M., Leblanc, Thierry, Paley, Carole, Kang, Elizabeth M., Leder, Eva Judmann, Atsidaftos, Eva, Shimamura, Akiko, Bessler, Monica, Glader, Bertil, Lipton, Jeffrey M., Vlachos, Adrianna, Ball, Sarah, Dahl, Niklas, Alter, Blanche P., Sheth, Sujit, Ramenghi, Ugo, Meerpohl, Joerg, Karlsson, Stefan, Liu, Johnson M., Leblanc, Thierry, Paley, Carole, Kang, Elizabeth M., Leder, Eva Judmann, Atsidaftos, Eva, Shimamura, Akiko, Bessler, Monica, Glader, Bertil, and Lipton, Jeffrey M.

Abstract

Diamond Blackfan anaemia (DBA) is a rare, genetically and clinically heterogeneous, inherited red cell aplasia. Classical DBA affects about seven per million live births and presents during the first year of life. However, as mutated genes have been discovered in DBA, non-classical cases with less distinct phenotypes are being described in adults as well as children. In caring for these patients it is often difficult to have a clear understanding of the treatment options and their outcomes because of the lack of complete information on the natural history of the disease. The purpose of this document is to review the criteria for diagnosis, evaluate the available treatment options, including corticosteroid and transfusion therapies and stem cell transplantation, and propose a plan for optimizing patient care. Congenital anomalies, mode of inheritance, cancer predisposition, and pregnancy in DBA are also reviewed. Evidence-based conclusions will be made when possible; however, as in many rare diseases, the data are often anecdotal and the recommendations are based upon the best judgment of experienced clinicians. The recommendations regarding the diagnosis and management described in this report are the result of deliberations and discussions at an international consensus conference.

Published
2008
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13. Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history of MYH9-related disease.

Author

Pecci, Alessandro, Panza, Emanuele, Pujol-Moix, Núria, Klersy, Catherine, Di Bari, Filomena, Bozzi, Valeria, Gresele, Paolo, Lethagen, Stefan, Fabris, Fabrizio, Dufour, Carlo, Granata, Antonio, Doubek, Michael, Pecoraro, Carmine, Koivisto, Pasi A, Heller, Paula G, Iolascon, Achille, Alvisi, Patrizia, Schwabe, Dirk, De Candia, Erica, Rocca, Bianca, Russo, Umberto, Ramenghi, Ugo, Noris, Patrizia, Seri, Marco, Balduini, Carlo L, Savoia, Anna, Pecci, Alessandro, Panza, Emanuele, Pujol-Moix, Núria, Klersy, Catherine, Di Bari, Filomena, Bozzi, Valeria, Gresele, Paolo, Lethagen, Stefan, Fabris, Fabrizio, Dufour, Carlo, Granata, Antonio, Doubek, Michael, Pecoraro, Carmine, Koivisto, Pasi A, Heller, Paula G, Iolascon, Achille, Alvisi, Patrizia, Schwabe, Dirk, De Candia, Erica, Rocca, Bianca, Russo, Umberto, Ramenghi, Ugo, Noris, Patrizia, Seri, Marco, Balduini, Carlo L, and Savoia, Anna

Published
2008

14. Variations of the perforin gene in patients with autoimmunity/lymphoproliferation and defective Fas function

Author

Clementi, Rita, Chiocchetti, Annalisa, Cappellano, Giuseppe, Cerutti, Elisa, Ferretti, Massimo, Orilieri, Elisabetta, Dianzani, Irma, Ferrarini, Marina, Bregni, Marco, Danesino, Cesare, Bozzi, Valeria, Putti, Maria Caterina, Cerutti, Franco, Cometa, Angela, Locatelli, Franco, Maccario, Rita, Ramenghi, Ugo, Dianzani, Umberto, Locatelli, Franco (ORCID:0000-0002-7976-3654), Clementi, Rita, Chiocchetti, Annalisa, Cappellano, Giuseppe, Cerutti, Elisa, Ferretti, Massimo, Orilieri, Elisabetta, Dianzani, Irma, Ferrarini, Marina, Bregni, Marco, Danesino, Cesare, Bozzi, Valeria, Putti, Maria Caterina, Cerutti, Franco, Cometa, Angela, Locatelli, Franco, Maccario, Rita, Ramenghi, Ugo, Dianzani, Umberto, and Locatelli, Franco (ORCID:0000-0002-7976-3654)

Abstract

Mutations decreasing function of the Fas death receptor cause the autoimmune lymphoproliferative syndrome (ALPS) with autoimmune manifestations, spleen/lymph node enlargement, and expansion of CD4/CD8-negative T cells. Dianzani Autoimmune Lymphoproliferative Disease (DALD) is a variant lacking this expansion. Perforin is involved in cell-mediated cytotoxicity and its biallelic mutations cause familial hemophagocytic lympho-histiocytosis (HLH). We previously described an ALPS patient carrying het-erozygous mutations of the Fas and perforin genes and suggested that they concurred in ALPS. This work extends the analysis to 14 ALPS, 28 DALD, and 816 controls, and detects an N252S amino acid substitution in 2 ALPS, and an A91V amino acid substitution in 6 DALD. N252S conferred an OR = 62.7 (P =.0016) for ALPS and A91V conferred an OR = 3 (P =.016) for DALD. Copresence of A91V and variations of the osteopontin gene previously associated with DALD conferred an OR = 17 (P =.0007) for DALD. In one N252S patient, NK activity was strikingly defective in early childhood, but became normal in late childhood. A91V patients displayed lower NK activity than controls. These data suggest that perforin variations are a susceptibility factor for ALPS/DALD development in subjects with defective Fas function and may influence disease expression.

Published
2006

15. Interactions between RPS19, mutated in Diamond-Blackfan anemia, and the PIM-1 oncoprotein.

Author

Chiocchetti, Annalisa, Gibello, Luisa, Carando, Adriana, Aspesi, Anna, Secco, Paola, Garelli, Emanuela, Loreni, Fabrizio, Angelini, Mara, Biava, Alessandra, Dahl, Niklas, Dianzani, Umberto, Ramenghi, Ugo, Santoro, Claudio, Dianzani, Irma, Chiocchetti, Annalisa, Gibello, Luisa, Carando, Adriana, Aspesi, Anna, Secco, Paola, Garelli, Emanuela, Loreni, Fabrizio, Angelini, Mara, Biava, Alessandra, Dahl, Niklas, Dianzani, Umberto, Ramenghi, Ugo, Santoro, Claudio, and Dianzani, Irma

Published
2005

16. A proportion of patients with lymphoma may harbor mutations of the perforin gene

Author

Clementi, Rita, Locatelli, Franco, Dupré, Loïc, Garaventa, Alberto, Emmi, Lorenzo, Bregni, Marco, Cefalo, Graziella, Moretta, Antonia, Danesino, Cesare, Comis, Margherita, Pession, Andrea, Ramenghi, Ugo, Maccario, Rita, Aricò, Maurizio, Roncarolo, Maria Grazia, Locatelli, Franco (ORCID:0000-0002-7976-3654), Clementi, Rita, Locatelli, Franco, Dupré, Loïc, Garaventa, Alberto, Emmi, Lorenzo, Bregni, Marco, Cefalo, Graziella, Moretta, Antonia, Danesino, Cesare, Comis, Margherita, Pession, Andrea, Ramenghi, Ugo, Maccario, Rita, Aricò, Maurizio, Roncarolo, Maria Grazia, and Locatelli, Franco (ORCID:0000-0002-7976-3654)

Abstract

Perforin mutations have been demonstrated in a proportion of patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH). In the present study, we evaluated whether some patients with lymphoma sharing clinical characteristics with HLH might harbor mutations of the perforin gene. We analyzed 29 patients and found that 4 patients, who developed either Hodgkin or non-Hodgkin lymphoma, had biallelic mutations of the perforin gene. One of these 4 patients, a 19-year-old female with T-cell lymphoma, had a brother carrying the same mutations who developed HLH. In 2 of the 4 patients with biallelic mutations of the perforin gene, we evaluated perforin expression by flow cytometry and natural killer (NK) activity and both were found to be absent. Moreover, we documented the presence of monoallelic mutations of the perforin gene in 4 more patients. One of these 4 latter patients also carried a mutation of the Fas gene. These data indicate that perforin deficiency, either alone or in combination with other mutations of genes involved in lymphocyte survival or functional activity, may be present in patients with lymphoma. These findings suggest that perforin also plays a key role in the mechanisms of immune surveillance that prevent tumor growth and/or development.

Published
2005

17. Rituximab for the treatment of refractory autoimmune hemolytic anemia in children

Author

Zecca, Marco, Nobili, Bruno, Ramenghi, Ugo, Perrotta, Silverio, Amendola, Giovanni, Rosito, Pasquale, Jankovic, Momcilo, Pierani, Paolo, De Stefano, Piero, Bonora, Mario Regazzi, Locatelli, Franco, Locatelli, Franco (ORCID:0000-0002-7976-3654), Zecca, Marco, Nobili, Bruno, Ramenghi, Ugo, Perrotta, Silverio, Amendola, Giovanni, Rosito, Pasquale, Jankovic, Momcilo, Pierani, Paolo, De Stefano, Piero, Bonora, Mario Regazzi, Locatelli, Franco, and Locatelli, Franco (ORCID:0000-0002-7976-3654)

Abstract

Autoimmune hemolytic anemia (AIHA) in children is sometimes characterized by a severe course, requiring prolonged administration of I Immunosuppressive therapy. Rituximab is able to cause selective in vivo destruction of B lymphocytes, with abrogation of antibody production. In a prospective study, we have evaluated the use of rituximab for the treatment of AIHA resistant to conventional treatment. Fifteen children with AIHA were given rituximab, 375 mg/m(2)/dose for a median of 3 weekly doses. All patients had previously received 2 or more courses of immunosuppressive therapy; 2 patients had undergone splenectomy. After completing treatment, all children received intravenous immunoglobulin for 6 months. Treatment was well tolerated.,With a medium follow-up of 13 months, 13 patients (87%) responded, whereas patients did not show any improvement. Median hemoglobin levels increased from 7.7 g/dL to a 2-month posttreatment level of 11.8 g/dL (P < .001). Median absolute reticulocyte counts decreased from 236 to 109 X 10(9)/L (P < .01). An increase in platelet count was observed in patients with concomitant thrombocytopenia (Evans syndrome). Three responder patients had relapse, 7, 8, and 10 months after rituximab infusion, respectively. All 3 children received 6 second course of rituximab, again achieving disease remission. Our data indicate that rituximab is both safe and effective in reducing or even abolishing hemolysis in children with AIHA and that a sustained response can be achieved in the majority of cases. Disease may recur, but a second treatment course may be successful in controlling the disease. (C) 206 by The American Society of Hematology.

Published
2003

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