Immunophenotype anomalies predict the development of autoimmune cytopenia in 22q11.2 Deletion Syndrome

Davide Montin, Agostina Marolda, Francesco Licciardi, Francesca Robasto, Silvia Di Cesare, Emanuela Ricotti, Francesca Ferro, Giacomo Scaioli, Carmela Giancotta, Donato Amodio, Francesca Conti, Giuliana Giardino, Lucia Leonardi, Silvia Ricci, Stefano Volpi, Lucia Augusta Baselli, Chiara Azzari, Grazia Bossi, Rita Consolini, Rosa Maria DellepianeMarzia Duse, Marco Gattorno, Baldassarre Martire, Maria Caterina Putti, Annarosa Soresina, Alessandro Plebani, Ugo Ramenghi, Silvana Martino, Claudio Pignata, Caterina Cancrini

Research output: Contribution to journalArticle

Abstract

BACKGROUND: patients with 22q11.2DS may develop severe thrombocytopenic purpura (ITP) and hemolytic anemia (AIHA). There are no reliable predictors for the development of hematologic autoimmunity (HA) in these patients.

OBJECTIVE: describe the peculiar B and T subpopulations defects in 22q11DS patients that have developed HA and test if these defects precede the development of HA.

METHODS: We performed a case-control multicenter study. Patients with HA were compared with a control population of 22q11.2DS without hematologic autoimmunity (non-HA). A complete immunological evaluation was performed at diagnosis and at last follow-up including extensive T and B phenotype.

RESULTS: Immunophenotype at last follow-up was available in 23 HA and 45 non-HA patients. HA patients had significantly decreased percentage of naïve CD4+ cells, (26,8% vs 43,2%, p=0,003) and recent thymic emigrants (48,6% vs 80,5%, p=0,046); decreased class-switched B cells (2,0% vs 5,9% p=0,04) and increased naive B cells (83,5% vs 71,4%, p=0,02); increased CD16+/56+ both in absolute number (312 vs 199, p=0,009) and percentage (20,0% vs 13,0%, p=0,03). Immunophenotype was performed in 36 patients (11 HA and 25 non-HA) at diagnosis. Odds ratio (OR) of immune cytopenia were estimated for both CD4 naïve ≤30% (OR 14.0 p=0.002) and for SMB ≤2% (OR 44.0 p=0.01). The estimated survival curves reached statistical significance respectively p=0.0001 and p=0.002.

CONCLUSION: Among 22q11.2DS patients those with HA have characteristic lymphocytes anomalies that appear considerably before HA onset. Systematic immunophenotyping of 22q11.2DS patients at diagnosis is advisable for early identification of patients at risk for this severe complication.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology: In Practice
DOIs
Publication statusE-pub ahead of print - Mar 25 2019

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DiGeorge Syndrome
Autoimmunity
Odds Ratio
B-Lymphocytes
Thrombocytopenic Purpura
Inosine Triphosphate
Immunophenotyping
Hemolytic Anemia
Hematologic Tests
Multicenter Studies

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Immunophenotype anomalies predict the development of autoimmune cytopenia in 22q11.2 Deletion Syndrome. / Montin, Davide; Marolda, Agostina; Licciardi, Francesco; Robasto, Francesca; Di Cesare, Silvia; Ricotti, Emanuela; Ferro, Francesca; Scaioli, Giacomo; Giancotta, Carmela; Amodio, Donato; Conti, Francesca; Giardino, Giuliana; Leonardi, Lucia; Ricci, Silvia; Volpi, Stefano; Baselli, Lucia Augusta; Azzari, Chiara; Bossi, Grazia; Consolini, Rita; Dellepiane, Rosa Maria; Duse, Marzia; Gattorno, Marco; Martire, Baldassarre; Caterina Putti, Maria; Soresina, Annarosa; Plebani, Alessandro; Ramenghi, Ugo; Martino, Silvana; Pignata, Claudio; Cancrini, Caterina.

In: Journal of Allergy and Clinical Immunology: In Practice, 25.03.2019.

Research output: Contribution to journalArticle

Montin, D, Marolda, A, Licciardi, F, Robasto, F, Di Cesare, S, Ricotti, E, Ferro, F, Scaioli, G, Giancotta, C, Amodio, D, Conti, F, Giardino, G, Leonardi, L, Ricci, S, Volpi, S, Baselli, LA, Azzari, C, Bossi, G, Consolini, R, Dellepiane, RM, Duse, M, Gattorno, M, Martire, B, Caterina Putti, M, Soresina, A, Plebani, A, Ramenghi, U, Martino, S, Pignata, C & Cancrini, C 2019, 'Immunophenotype anomalies predict the development of autoimmune cytopenia in 22q11.2 Deletion Syndrome', Journal of Allergy and Clinical Immunology: In Practice. https://doi.org/10.1016/j.jaip.2019.03.014
Montin, Davide ; Marolda, Agostina ; Licciardi, Francesco ; Robasto, Francesca ; Di Cesare, Silvia ; Ricotti, Emanuela ; Ferro, Francesca ; Scaioli, Giacomo ; Giancotta, Carmela ; Amodio, Donato ; Conti, Francesca ; Giardino, Giuliana ; Leonardi, Lucia ; Ricci, Silvia ; Volpi, Stefano ; Baselli, Lucia Augusta ; Azzari, Chiara ; Bossi, Grazia ; Consolini, Rita ; Dellepiane, Rosa Maria ; Duse, Marzia ; Gattorno, Marco ; Martire, Baldassarre ; Caterina Putti, Maria ; Soresina, Annarosa ; Plebani, Alessandro ; Ramenghi, Ugo ; Martino, Silvana ; Pignata, Claudio ; Cancrini, Caterina. / Immunophenotype anomalies predict the development of autoimmune cytopenia in 22q11.2 Deletion Syndrome. In: Journal of Allergy and Clinical Immunology: In Practice. 2019.
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title = "Immunophenotype anomalies predict the development of autoimmune cytopenia in 22q11.2 Deletion Syndrome",
abstract = "BACKGROUND: patients with 22q11.2DS may develop severe thrombocytopenic purpura (ITP) and hemolytic anemia (AIHA). There are no reliable predictors for the development of hematologic autoimmunity (HA) in these patients.OBJECTIVE: describe the peculiar B and T subpopulations defects in 22q11DS patients that have developed HA and test if these defects precede the development of HA.METHODS: We performed a case-control multicenter study. Patients with HA were compared with a control population of 22q11.2DS without hematologic autoimmunity (non-HA). A complete immunological evaluation was performed at diagnosis and at last follow-up including extensive T and B phenotype.RESULTS: Immunophenotype at last follow-up was available in 23 HA and 45 non-HA patients. HA patients had significantly decreased percentage of na{\"i}ve CD4+ cells, (26,8{\%} vs 43,2{\%}, p=0,003) and recent thymic emigrants (48,6{\%} vs 80,5{\%}, p=0,046); decreased class-switched B cells (2,0{\%} vs 5,9{\%} p=0,04) and increased naive B cells (83,5{\%} vs 71,4{\%}, p=0,02); increased CD16+/56+ both in absolute number (312 vs 199, p=0,009) and percentage (20,0{\%} vs 13,0{\%}, p=0,03). Immunophenotype was performed in 36 patients (11 HA and 25 non-HA) at diagnosis. Odds ratio (OR) of immune cytopenia were estimated for both CD4 na{\"i}ve ≤30{\%} (OR 14.0 p=0.002) and for SMB ≤2{\%} (OR 44.0 p=0.01). The estimated survival curves reached statistical significance respectively p=0.0001 and p=0.002.CONCLUSION: Among 22q11.2DS patients those with HA have characteristic lymphocytes anomalies that appear considerably before HA onset. Systematic immunophenotyping of 22q11.2DS patients at diagnosis is advisable for early identification of patients at risk for this severe complication.",
author = "Davide Montin and Agostina Marolda and Francesco Licciardi and Francesca Robasto and {Di Cesare}, Silvia and Emanuela Ricotti and Francesca Ferro and Giacomo Scaioli and Carmela Giancotta and Donato Amodio and Francesca Conti and Giuliana Giardino and Lucia Leonardi and Silvia Ricci and Stefano Volpi and Baselli, {Lucia Augusta} and Chiara Azzari and Grazia Bossi and Rita Consolini and Dellepiane, {Rosa Maria} and Marzia Duse and Marco Gattorno and Baldassarre Martire and {Caterina Putti}, Maria and Annarosa Soresina and Alessandro Plebani and Ugo Ramenghi and Silvana Martino and Claudio Pignata and Caterina Cancrini",
note = "Copyright {\circledC} 2019. Published by Elsevier Inc.",
year = "2019",
month = "3",
day = "25",
doi = "10.1016/j.jaip.2019.03.014",
language = "English",
journal = "Journal of Allergy and Clinical Immunology: In Practice",
issn = "2213-2198",
publisher = "American Academy of Allergy, Asthma and Immunology",

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TY - JOUR

T1 - Immunophenotype anomalies predict the development of autoimmune cytopenia in 22q11.2 Deletion Syndrome

AU - Montin, Davide

AU - Marolda, Agostina

AU - Licciardi, Francesco

AU - Robasto, Francesca

AU - Di Cesare, Silvia

AU - Ricotti, Emanuela

AU - Ferro, Francesca

AU - Scaioli, Giacomo

AU - Giancotta, Carmela

AU - Amodio, Donato

AU - Conti, Francesca

AU - Giardino, Giuliana

AU - Leonardi, Lucia

AU - Ricci, Silvia

AU - Volpi, Stefano

AU - Baselli, Lucia Augusta

AU - Azzari, Chiara

AU - Bossi, Grazia

AU - Consolini, Rita

AU - Dellepiane, Rosa Maria

AU - Duse, Marzia

AU - Gattorno, Marco

AU - Martire, Baldassarre

AU - Caterina Putti, Maria

AU - Soresina, Annarosa

AU - Plebani, Alessandro

AU - Ramenghi, Ugo

AU - Martino, Silvana

AU - Pignata, Claudio

AU - Cancrini, Caterina

N1 - Copyright © 2019. Published by Elsevier Inc.

PY - 2019/3/25

Y1 - 2019/3/25

N2 - BACKGROUND: patients with 22q11.2DS may develop severe thrombocytopenic purpura (ITP) and hemolytic anemia (AIHA). There are no reliable predictors for the development of hematologic autoimmunity (HA) in these patients.OBJECTIVE: describe the peculiar B and T subpopulations defects in 22q11DS patients that have developed HA and test if these defects precede the development of HA.METHODS: We performed a case-control multicenter study. Patients with HA were compared with a control population of 22q11.2DS without hematologic autoimmunity (non-HA). A complete immunological evaluation was performed at diagnosis and at last follow-up including extensive T and B phenotype.RESULTS: Immunophenotype at last follow-up was available in 23 HA and 45 non-HA patients. HA patients had significantly decreased percentage of naïve CD4+ cells, (26,8% vs 43,2%, p=0,003) and recent thymic emigrants (48,6% vs 80,5%, p=0,046); decreased class-switched B cells (2,0% vs 5,9% p=0,04) and increased naive B cells (83,5% vs 71,4%, p=0,02); increased CD16+/56+ both in absolute number (312 vs 199, p=0,009) and percentage (20,0% vs 13,0%, p=0,03). Immunophenotype was performed in 36 patients (11 HA and 25 non-HA) at diagnosis. Odds ratio (OR) of immune cytopenia were estimated for both CD4 naïve ≤30% (OR 14.0 p=0.002) and for SMB ≤2% (OR 44.0 p=0.01). The estimated survival curves reached statistical significance respectively p=0.0001 and p=0.002.CONCLUSION: Among 22q11.2DS patients those with HA have characteristic lymphocytes anomalies that appear considerably before HA onset. Systematic immunophenotyping of 22q11.2DS patients at diagnosis is advisable for early identification of patients at risk for this severe complication.

AB - BACKGROUND: patients with 22q11.2DS may develop severe thrombocytopenic purpura (ITP) and hemolytic anemia (AIHA). There are no reliable predictors for the development of hematologic autoimmunity (HA) in these patients.OBJECTIVE: describe the peculiar B and T subpopulations defects in 22q11DS patients that have developed HA and test if these defects precede the development of HA.METHODS: We performed a case-control multicenter study. Patients with HA were compared with a control population of 22q11.2DS without hematologic autoimmunity (non-HA). A complete immunological evaluation was performed at diagnosis and at last follow-up including extensive T and B phenotype.RESULTS: Immunophenotype at last follow-up was available in 23 HA and 45 non-HA patients. HA patients had significantly decreased percentage of naïve CD4+ cells, (26,8% vs 43,2%, p=0,003) and recent thymic emigrants (48,6% vs 80,5%, p=0,046); decreased class-switched B cells (2,0% vs 5,9% p=0,04) and increased naive B cells (83,5% vs 71,4%, p=0,02); increased CD16+/56+ both in absolute number (312 vs 199, p=0,009) and percentage (20,0% vs 13,0%, p=0,03). Immunophenotype was performed in 36 patients (11 HA and 25 non-HA) at diagnosis. Odds ratio (OR) of immune cytopenia were estimated for both CD4 naïve ≤30% (OR 14.0 p=0.002) and for SMB ≤2% (OR 44.0 p=0.01). The estimated survival curves reached statistical significance respectively p=0.0001 and p=0.002.CONCLUSION: Among 22q11.2DS patients those with HA have characteristic lymphocytes anomalies that appear considerably before HA onset. Systematic immunophenotyping of 22q11.2DS patients at diagnosis is advisable for early identification of patients at risk for this severe complication.

U2 - 10.1016/j.jaip.2019.03.014

DO - 10.1016/j.jaip.2019.03.014

M3 - Article

C2 - 30922987

JO - Journal of Allergy and Clinical Immunology: In Practice

JF - Journal of Allergy and Clinical Immunology: In Practice

SN - 2213-2198

ER -