Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients

Purpose We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Methods Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next...
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Autor*in:	Cifaldi, Cristina [verfasserIn] Rivalta, Beatrice Amodio, Donato Mattia, Algeri Pacillo, Lucia Di Cesare, Silvia Chiriaco, Maria Ursu, Giorgiana Madalina Cotugno, Nicola Giancotta, Carmela Manno, Emma C. Santilli, Veronica Zangari, Paola Federica, Galaverna Palumbo, Giuseppe Merli, Pietro Palma, Paolo Rossi, Paolo Di Matteo, Gigliola Locatelli, Franco Finocchi, Andrea Cancrini, Caterina

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	RAG deficiency RAG1/RAG2 Hypomorphic mutation CID phenotypes Cytopenia

Anmerkung:	© The Author(s) 2021

Übergeordnetes Werk:	Enthalten in: Journal of clinical immunology - Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981, 42(2021), 1 vom: 18. Okt., Seite 130-145
Übergeordnetes Werk:	volume:42 ; year:2021 ; number:1 ; day:18 ; month:10 ; pages:130-145

Links:	Volltext

DOI / URN:	10.1007/s10875-021-01130-3

Katalog-ID:	SPR046172793

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100	1		\|a Cifaldi, Cristina \|e verfasserin \|0 (orcid)0000-0002-7170-7279 \|4 aut
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520			\|a Purpose We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Methods Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next generation sequencing (NGS) as appropriate. Results Patients represented a broad spectrum of RAG deficiencies: SCID, OS, LS/AS, and CID. Three novel mutations in RAG1 gene and one in RAG2 were reported. The primary symptom at presentation was infections (81.8%). Infections and autoimmunity occurred together in the majority of cases (63.6%). Fifteen out of 22 (68.2%) patients presented autoimmune or inflammatory manifestations. Five patients experienced severe autoimmune cytopenia refractory to different lines of therapy. Total lymphocytes count was reduced or almost lacking in SCID group and higher in OS patients. B lymphocytes were variably detected in LS/AS and CID groups. Eighteen patients underwent HSCT permitting definitive control of autoimmune/hyperinflammatory manifestations in twelve of them (80%). Conclusion We reinforce the notion that different clinical phenotype can be found in patients with identical mutations even within the same family. Infections may influence genotype–phenotype correlation and function as trigger for immune dysregulation or autoimmune manifestations. Severe and early autoimmune refractory cytopenia is frequent and could be the first symptom of onset. Prompt recognition of RAG deficiency in patients with early onset of autoimmune/hyperinflammatory manifestations could contribute to the choice of a timely and specific treatment preventing the onset of other complications.
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700	1		\|a Pacillo, Lucia \|4 aut
700	1		\|a Di Cesare, Silvia \|4 aut
700	1		\|a Chiriaco, Maria \|4 aut
700	1		\|a Ursu, Giorgiana Madalina \|4 aut
700	1		\|a Cotugno, Nicola \|4 aut
700	1		\|a Giancotta, Carmela \|4 aut
700	1		\|a Manno, Emma C. \|4 aut
700	1		\|a Santilli, Veronica \|4 aut
700	1		\|a Zangari, Paola \|4 aut
700	1		\|a Federica, Galaverna \|4 aut
700	1		\|a Palumbo, Giuseppe \|4 aut
700	1		\|a Merli, Pietro \|4 aut
700	1		\|a Palma, Paolo \|4 aut
700	1		\|a Rossi, Paolo \|4 aut
700	1		\|a Di Matteo, Gigliola \|4 aut
700	1		\|a Locatelli, Franco \|4 aut
700	1		\|a Finocchi, Andrea \|4 aut
700	1		\|a Cancrini, Caterina \|4 aut
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publishDate	2021
allfields	10.1007/s10875-021-01130-3 doi (DE-627)SPR046172793 (SPR)s10875-021-01130-3-e DE-627 ger DE-627 rakwb eng Cifaldi, Cristina verfasserin (orcid)0000-0002-7170-7279 aut Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Purpose We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Methods Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next generation sequencing (NGS) as appropriate. Results Patients represented a broad spectrum of RAG deficiencies: SCID, OS, LS/AS, and CID. Three novel mutations in RAG1 gene and one in RAG2 were reported. The primary symptom at presentation was infections (81.8%). Infections and autoimmunity occurred together in the majority of cases (63.6%). Fifteen out of 22 (68.2%) patients presented autoimmune or inflammatory manifestations. Five patients experienced severe autoimmune cytopenia refractory to different lines of therapy. Total lymphocytes count was reduced or almost lacking in SCID group and higher in OS patients. B lymphocytes were variably detected in LS/AS and CID groups. Eighteen patients underwent HSCT permitting definitive control of autoimmune/hyperinflammatory manifestations in twelve of them (80%). Conclusion We reinforce the notion that different clinical phenotype can be found in patients with identical mutations even within the same family. Infections may influence genotype–phenotype correlation and function as trigger for immune dysregulation or autoimmune manifestations. Severe and early autoimmune refractory cytopenia is frequent and could be the first symptom of onset. Prompt recognition of RAG deficiency in patients with early onset of autoimmune/hyperinflammatory manifestations could contribute to the choice of a timely and specific treatment preventing the onset of other complications. RAG deficiency (dpeaa)DE-He213 RAG1/RAG2 (dpeaa)DE-He213 Hypomorphic mutation (dpeaa)DE-He213 CID phenotypes (dpeaa)DE-He213 Cytopenia (dpeaa)DE-He213 Rivalta, Beatrice aut Amodio, Donato aut Mattia, Algeri aut Pacillo, Lucia aut Di Cesare, Silvia aut Chiriaco, Maria aut Ursu, Giorgiana Madalina aut Cotugno, Nicola aut Giancotta, Carmela aut Manno, Emma C. aut Santilli, Veronica aut Zangari, Paola aut Federica, Galaverna aut Palumbo, Giuseppe aut Merli, Pietro aut Palma, Paolo aut Rossi, Paolo aut Di Matteo, Gigliola aut Locatelli, Franco aut Finocchi, Andrea aut Cancrini, Caterina aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 42(2021), 1 vom: 18. Okt., Seite 130-145 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:42 year:2021 number:1 day:18 month:10 pages:130-145 https://dx.doi.org/10.1007/s10875-021-01130-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 42 2021 1 18 10 130-145
spelling	10.1007/s10875-021-01130-3 doi (DE-627)SPR046172793 (SPR)s10875-021-01130-3-e DE-627 ger DE-627 rakwb eng Cifaldi, Cristina verfasserin (orcid)0000-0002-7170-7279 aut Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Purpose We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Methods Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next generation sequencing (NGS) as appropriate. Results Patients represented a broad spectrum of RAG deficiencies: SCID, OS, LS/AS, and CID. Three novel mutations in RAG1 gene and one in RAG2 were reported. The primary symptom at presentation was infections (81.8%). Infections and autoimmunity occurred together in the majority of cases (63.6%). Fifteen out of 22 (68.2%) patients presented autoimmune or inflammatory manifestations. Five patients experienced severe autoimmune cytopenia refractory to different lines of therapy. Total lymphocytes count was reduced or almost lacking in SCID group and higher in OS patients. B lymphocytes were variably detected in LS/AS and CID groups. Eighteen patients underwent HSCT permitting definitive control of autoimmune/hyperinflammatory manifestations in twelve of them (80%). Conclusion We reinforce the notion that different clinical phenotype can be found in patients with identical mutations even within the same family. Infections may influence genotype–phenotype correlation and function as trigger for immune dysregulation or autoimmune manifestations. Severe and early autoimmune refractory cytopenia is frequent and could be the first symptom of onset. Prompt recognition of RAG deficiency in patients with early onset of autoimmune/hyperinflammatory manifestations could contribute to the choice of a timely and specific treatment preventing the onset of other complications. RAG deficiency (dpeaa)DE-He213 RAG1/RAG2 (dpeaa)DE-He213 Hypomorphic mutation (dpeaa)DE-He213 CID phenotypes (dpeaa)DE-He213 Cytopenia (dpeaa)DE-He213 Rivalta, Beatrice aut Amodio, Donato aut Mattia, Algeri aut Pacillo, Lucia aut Di Cesare, Silvia aut Chiriaco, Maria aut Ursu, Giorgiana Madalina aut Cotugno, Nicola aut Giancotta, Carmela aut Manno, Emma C. aut Santilli, Veronica aut Zangari, Paola aut Federica, Galaverna aut Palumbo, Giuseppe aut Merli, Pietro aut Palma, Paolo aut Rossi, Paolo aut Di Matteo, Gigliola aut Locatelli, Franco aut Finocchi, Andrea aut Cancrini, Caterina aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 42(2021), 1 vom: 18. Okt., Seite 130-145 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:42 year:2021 number:1 day:18 month:10 pages:130-145 https://dx.doi.org/10.1007/s10875-021-01130-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 42 2021 1 18 10 130-145
allfields_unstemmed	10.1007/s10875-021-01130-3 doi (DE-627)SPR046172793 (SPR)s10875-021-01130-3-e DE-627 ger DE-627 rakwb eng Cifaldi, Cristina verfasserin (orcid)0000-0002-7170-7279 aut Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Purpose We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Methods Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next generation sequencing (NGS) as appropriate. Results Patients represented a broad spectrum of RAG deficiencies: SCID, OS, LS/AS, and CID. Three novel mutations in RAG1 gene and one in RAG2 were reported. The primary symptom at presentation was infections (81.8%). Infections and autoimmunity occurred together in the majority of cases (63.6%). Fifteen out of 22 (68.2%) patients presented autoimmune or inflammatory manifestations. Five patients experienced severe autoimmune cytopenia refractory to different lines of therapy. Total lymphocytes count was reduced or almost lacking in SCID group and higher in OS patients. B lymphocytes were variably detected in LS/AS and CID groups. Eighteen patients underwent HSCT permitting definitive control of autoimmune/hyperinflammatory manifestations in twelve of them (80%). Conclusion We reinforce the notion that different clinical phenotype can be found in patients with identical mutations even within the same family. Infections may influence genotype–phenotype correlation and function as trigger for immune dysregulation or autoimmune manifestations. Severe and early autoimmune refractory cytopenia is frequent and could be the first symptom of onset. Prompt recognition of RAG deficiency in patients with early onset of autoimmune/hyperinflammatory manifestations could contribute to the choice of a timely and specific treatment preventing the onset of other complications. RAG deficiency (dpeaa)DE-He213 RAG1/RAG2 (dpeaa)DE-He213 Hypomorphic mutation (dpeaa)DE-He213 CID phenotypes (dpeaa)DE-He213 Cytopenia (dpeaa)DE-He213 Rivalta, Beatrice aut Amodio, Donato aut Mattia, Algeri aut Pacillo, Lucia aut Di Cesare, Silvia aut Chiriaco, Maria aut Ursu, Giorgiana Madalina aut Cotugno, Nicola aut Giancotta, Carmela aut Manno, Emma C. aut Santilli, Veronica aut Zangari, Paola aut Federica, Galaverna aut Palumbo, Giuseppe aut Merli, Pietro aut Palma, Paolo aut Rossi, Paolo aut Di Matteo, Gigliola aut Locatelli, Franco aut Finocchi, Andrea aut Cancrini, Caterina aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 42(2021), 1 vom: 18. Okt., Seite 130-145 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:42 year:2021 number:1 day:18 month:10 pages:130-145 https://dx.doi.org/10.1007/s10875-021-01130-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 42 2021 1 18 10 130-145
allfieldsGer	10.1007/s10875-021-01130-3 doi (DE-627)SPR046172793 (SPR)s10875-021-01130-3-e DE-627 ger DE-627 rakwb eng Cifaldi, Cristina verfasserin (orcid)0000-0002-7170-7279 aut Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Purpose We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Methods Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next generation sequencing (NGS) as appropriate. Results Patients represented a broad spectrum of RAG deficiencies: SCID, OS, LS/AS, and CID. Three novel mutations in RAG1 gene and one in RAG2 were reported. The primary symptom at presentation was infections (81.8%). Infections and autoimmunity occurred together in the majority of cases (63.6%). Fifteen out of 22 (68.2%) patients presented autoimmune or inflammatory manifestations. Five patients experienced severe autoimmune cytopenia refractory to different lines of therapy. Total lymphocytes count was reduced or almost lacking in SCID group and higher in OS patients. B lymphocytes were variably detected in LS/AS and CID groups. Eighteen patients underwent HSCT permitting definitive control of autoimmune/hyperinflammatory manifestations in twelve of them (80%). Conclusion We reinforce the notion that different clinical phenotype can be found in patients with identical mutations even within the same family. Infections may influence genotype–phenotype correlation and function as trigger for immune dysregulation or autoimmune manifestations. Severe and early autoimmune refractory cytopenia is frequent and could be the first symptom of onset. Prompt recognition of RAG deficiency in patients with early onset of autoimmune/hyperinflammatory manifestations could contribute to the choice of a timely and specific treatment preventing the onset of other complications. RAG deficiency (dpeaa)DE-He213 RAG1/RAG2 (dpeaa)DE-He213 Hypomorphic mutation (dpeaa)DE-He213 CID phenotypes (dpeaa)DE-He213 Cytopenia (dpeaa)DE-He213 Rivalta, Beatrice aut Amodio, Donato aut Mattia, Algeri aut Pacillo, Lucia aut Di Cesare, Silvia aut Chiriaco, Maria aut Ursu, Giorgiana Madalina aut Cotugno, Nicola aut Giancotta, Carmela aut Manno, Emma C. aut Santilli, Veronica aut Zangari, Paola aut Federica, Galaverna aut Palumbo, Giuseppe aut Merli, Pietro aut Palma, Paolo aut Rossi, Paolo aut Di Matteo, Gigliola aut Locatelli, Franco aut Finocchi, Andrea aut Cancrini, Caterina aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 42(2021), 1 vom: 18. Okt., Seite 130-145 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:42 year:2021 number:1 day:18 month:10 pages:130-145 https://dx.doi.org/10.1007/s10875-021-01130-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 42 2021 1 18 10 130-145
allfieldsSound	10.1007/s10875-021-01130-3 doi (DE-627)SPR046172793 (SPR)s10875-021-01130-3-e DE-627 ger DE-627 rakwb eng Cifaldi, Cristina verfasserin (orcid)0000-0002-7170-7279 aut Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2021 Purpose We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Methods Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next generation sequencing (NGS) as appropriate. Results Patients represented a broad spectrum of RAG deficiencies: SCID, OS, LS/AS, and CID. Three novel mutations in RAG1 gene and one in RAG2 were reported. The primary symptom at presentation was infections (81.8%). Infections and autoimmunity occurred together in the majority of cases (63.6%). Fifteen out of 22 (68.2%) patients presented autoimmune or inflammatory manifestations. Five patients experienced severe autoimmune cytopenia refractory to different lines of therapy. Total lymphocytes count was reduced or almost lacking in SCID group and higher in OS patients. B lymphocytes were variably detected in LS/AS and CID groups. Eighteen patients underwent HSCT permitting definitive control of autoimmune/hyperinflammatory manifestations in twelve of them (80%). Conclusion We reinforce the notion that different clinical phenotype can be found in patients with identical mutations even within the same family. Infections may influence genotype–phenotype correlation and function as trigger for immune dysregulation or autoimmune manifestations. Severe and early autoimmune refractory cytopenia is frequent and could be the first symptom of onset. Prompt recognition of RAG deficiency in patients with early onset of autoimmune/hyperinflammatory manifestations could contribute to the choice of a timely and specific treatment preventing the onset of other complications. RAG deficiency (dpeaa)DE-He213 RAG1/RAG2 (dpeaa)DE-He213 Hypomorphic mutation (dpeaa)DE-He213 CID phenotypes (dpeaa)DE-He213 Cytopenia (dpeaa)DE-He213 Rivalta, Beatrice aut Amodio, Donato aut Mattia, Algeri aut Pacillo, Lucia aut Di Cesare, Silvia aut Chiriaco, Maria aut Ursu, Giorgiana Madalina aut Cotugno, Nicola aut Giancotta, Carmela aut Manno, Emma C. aut Santilli, Veronica aut Zangari, Paola aut Federica, Galaverna aut Palumbo, Giuseppe aut Merli, Pietro aut Palma, Paolo aut Rossi, Paolo aut Di Matteo, Gigliola aut Locatelli, Franco aut Finocchi, Andrea aut Cancrini, Caterina aut Enthalten in Journal of clinical immunology Dordrecht [u.a.] : Springer Science + Business Media B.V, 1981 42(2021), 1 vom: 18. Okt., Seite 130-145 (DE-627)320573362 (DE-600)2016755-6 1573-2592 nnns volume:42 year:2021 number:1 day:18 month:10 pages:130-145 https://dx.doi.org/10.1007/s10875-021-01130-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 42 2021 1 18 10 130-145
language	English
source	Enthalten in Journal of clinical immunology 42(2021), 1 vom: 18. Okt., Seite 130-145 volume:42 year:2021 number:1 day:18 month:10 pages:130-145
sourceStr	Enthalten in Journal of clinical immunology 42(2021), 1 vom: 18. Okt., Seite 130-145 volume:42 year:2021 number:1 day:18 month:10 pages:130-145
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	RAG deficiency RAG1/RAG2 Hypomorphic mutation CID phenotypes Cytopenia
isfreeaccess_bool	true
container_title	Journal of clinical immunology
authorswithroles_txt_mv	Cifaldi, Cristina @@aut@@ Rivalta, Beatrice @@aut@@ Amodio, Donato @@aut@@ Mattia, Algeri @@aut@@ Pacillo, Lucia @@aut@@ Di Cesare, Silvia @@aut@@ Chiriaco, Maria @@aut@@ Ursu, Giorgiana Madalina @@aut@@ Cotugno, Nicola @@aut@@ Giancotta, Carmela @@aut@@ Manno, Emma C. @@aut@@ Santilli, Veronica @@aut@@ Zangari, Paola @@aut@@ Federica, Galaverna @@aut@@ Palumbo, Giuseppe @@aut@@ Merli, Pietro @@aut@@ Palma, Paolo @@aut@@ Rossi, Paolo @@aut@@ Di Matteo, Gigliola @@aut@@ Locatelli, Franco @@aut@@ Finocchi, Andrea @@aut@@ Cancrini, Caterina @@aut@@
publishDateDaySort_date	2021-10-18T00:00:00Z
hierarchy_top_id	320573362
id	SPR046172793
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR046172793</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519224051.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">220208s2021 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s10875-021-01130-3</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR046172793</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s10875-021-01130-3-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Cifaldi, Cristina</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-7170-7279</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2021</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s) 2021</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Purpose We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Methods Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next generation sequencing (NGS) as appropriate. Results Patients represented a broad spectrum of RAG deficiencies: SCID, OS, LS/AS, and CID. Three novel mutations in RAG1 gene and one in RAG2 were reported. The primary symptom at presentation was infections (81.8%). Infections and autoimmunity occurred together in the majority of cases (63.6%). Fifteen out of 22 (68.2%) patients presented autoimmune or inflammatory manifestations. Five patients experienced severe autoimmune cytopenia refractory to different lines of therapy. Total lymphocytes count was reduced or almost lacking in SCID group and higher in OS patients. B lymphocytes were variably detected in LS/AS and CID groups. Eighteen patients underwent HSCT permitting definitive control of autoimmune/hyperinflammatory manifestations in twelve of them (80%). Conclusion We reinforce the notion that different clinical phenotype can be found in patients with identical mutations even within the same family. Infections may influence genotype–phenotype correlation and function as trigger for immune dysregulation or autoimmune manifestations. Severe and early autoimmune refractory cytopenia is frequent and could be the first symptom of onset. 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author	Cifaldi, Cristina
spellingShingle	Cifaldi, Cristina misc RAG deficiency misc RAG1/RAG2 misc Hypomorphic mutation misc CID phenotypes misc Cytopenia Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients
authorStr	Cifaldi, Cristina
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topic_title	Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients RAG deficiency (dpeaa)DE-He213 RAG1/RAG2 (dpeaa)DE-He213 Hypomorphic mutation (dpeaa)DE-He213 CID phenotypes (dpeaa)DE-He213 Cytopenia (dpeaa)DE-He213
topic	misc RAG deficiency misc RAG1/RAG2 misc Hypomorphic mutation misc CID phenotypes misc Cytopenia
topic_unstemmed	misc RAG deficiency misc RAG1/RAG2 misc Hypomorphic mutation misc CID phenotypes misc Cytopenia
topic_browse	misc RAG deficiency misc RAG1/RAG2 misc Hypomorphic mutation misc CID phenotypes misc Cytopenia
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title	Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients
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title_full	Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients
author_sort	Cifaldi, Cristina
journal	Journal of clinical immunology
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author_browse	Cifaldi, Cristina Rivalta, Beatrice Amodio, Donato Mattia, Algeri Pacillo, Lucia Di Cesare, Silvia Chiriaco, Maria Ursu, Giorgiana Madalina Cotugno, Nicola Giancotta, Carmela Manno, Emma C. Santilli, Veronica Zangari, Paola Federica, Galaverna Palumbo, Giuseppe Merli, Pietro Palma, Paolo Rossi, Paolo Di Matteo, Gigliola Locatelli, Franco Finocchi, Andrea Cancrini, Caterina
container_volume	42
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author-letter	Cifaldi, Cristina
doi_str_mv	10.1007/s10875-021-01130-3
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title_sort	clinical, immunological, and molecular variability of rag deficiency: a retrospective analysis of 22 rag patients
title_auth	Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients
abstract	Purpose We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Methods Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next generation sequencing (NGS) as appropriate. Results Patients represented a broad spectrum of RAG deficiencies: SCID, OS, LS/AS, and CID. Three novel mutations in RAG1 gene and one in RAG2 were reported. The primary symptom at presentation was infections (81.8%). Infections and autoimmunity occurred together in the majority of cases (63.6%). Fifteen out of 22 (68.2%) patients presented autoimmune or inflammatory manifestations. Five patients experienced severe autoimmune cytopenia refractory to different lines of therapy. Total lymphocytes count was reduced or almost lacking in SCID group and higher in OS patients. B lymphocytes were variably detected in LS/AS and CID groups. Eighteen patients underwent HSCT permitting definitive control of autoimmune/hyperinflammatory manifestations in twelve of them (80%). Conclusion We reinforce the notion that different clinical phenotype can be found in patients with identical mutations even within the same family. Infections may influence genotype–phenotype correlation and function as trigger for immune dysregulation or autoimmune manifestations. Severe and early autoimmune refractory cytopenia is frequent and could be the first symptom of onset. Prompt recognition of RAG deficiency in patients with early onset of autoimmune/hyperinflammatory manifestations could contribute to the choice of a timely and specific treatment preventing the onset of other complications. © The Author(s) 2021
abstractGer	Purpose We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Methods Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next generation sequencing (NGS) as appropriate. Results Patients represented a broad spectrum of RAG deficiencies: SCID, OS, LS/AS, and CID. Three novel mutations in RAG1 gene and one in RAG2 were reported. The primary symptom at presentation was infections (81.8%). Infections and autoimmunity occurred together in the majority of cases (63.6%). Fifteen out of 22 (68.2%) patients presented autoimmune or inflammatory manifestations. Five patients experienced severe autoimmune cytopenia refractory to different lines of therapy. Total lymphocytes count was reduced or almost lacking in SCID group and higher in OS patients. B lymphocytes were variably detected in LS/AS and CID groups. Eighteen patients underwent HSCT permitting definitive control of autoimmune/hyperinflammatory manifestations in twelve of them (80%). Conclusion We reinforce the notion that different clinical phenotype can be found in patients with identical mutations even within the same family. Infections may influence genotype–phenotype correlation and function as trigger for immune dysregulation or autoimmune manifestations. Severe and early autoimmune refractory cytopenia is frequent and could be the first symptom of onset. Prompt recognition of RAG deficiency in patients with early onset of autoimmune/hyperinflammatory manifestations could contribute to the choice of a timely and specific treatment preventing the onset of other complications. © The Author(s) 2021
abstract_unstemmed	Purpose We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Methods Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next generation sequencing (NGS) as appropriate. Results Patients represented a broad spectrum of RAG deficiencies: SCID, OS, LS/AS, and CID. Three novel mutations in RAG1 gene and one in RAG2 were reported. The primary symptom at presentation was infections (81.8%). Infections and autoimmunity occurred together in the majority of cases (63.6%). Fifteen out of 22 (68.2%) patients presented autoimmune or inflammatory manifestations. Five patients experienced severe autoimmune cytopenia refractory to different lines of therapy. Total lymphocytes count was reduced or almost lacking in SCID group and higher in OS patients. B lymphocytes were variably detected in LS/AS and CID groups. Eighteen patients underwent HSCT permitting definitive control of autoimmune/hyperinflammatory manifestations in twelve of them (80%). Conclusion We reinforce the notion that different clinical phenotype can be found in patients with identical mutations even within the same family. Infections may influence genotype–phenotype correlation and function as trigger for immune dysregulation or autoimmune manifestations. Severe and early autoimmune refractory cytopenia is frequent and could be the first symptom of onset. Prompt recognition of RAG deficiency in patients with early onset of autoimmune/hyperinflammatory manifestations could contribute to the choice of a timely and specific treatment preventing the onset of other complications. © The Author(s) 2021
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title_short	Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients
url	https://dx.doi.org/10.1007/s10875-021-01130-3
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author2	Rivalta, Beatrice Amodio, Donato Mattia, Algeri Pacillo, Lucia Di Cesare, Silvia Chiriaco, Maria Ursu, Giorgiana Madalina Cotugno, Nicola Giancotta, Carmela Manno, Emma C. Santilli, Veronica Zangari, Paola Federica, Galaverna Palumbo, Giuseppe Merli, Pietro Palma, Paolo Rossi, Paolo Di Matteo, Gigliola Locatelli, Franco Finocchi, Andrea Cancrini, Caterina
author2Str	Rivalta, Beatrice Amodio, Donato Mattia, Algeri Pacillo, Lucia Di Cesare, Silvia Chiriaco, Maria Ursu, Giorgiana Madalina Cotugno, Nicola Giancotta, Carmela Manno, Emma C. Santilli, Veronica Zangari, Paola Federica, Galaverna Palumbo, Giuseppe Merli, Pietro Palma, Paolo Rossi, Paolo Di Matteo, Gigliola Locatelli, Franco Finocchi, Andrea Cancrini, Caterina
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doi_str	10.1007/s10875-021-01130-3
up_date	2024-07-03T20:50:28.914Z
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Clinical, Immunological, and Molecular Variability of RAG Deficiency: A Retrospective Analysis of 22 RAG Patients

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