Underlying Inborn Errors of Immunity in Patients With Evans Syndrome and Multilineage Cytopenias: A Single-Centre Analysis
BackgroundEvans syndrome (ES) is a rare disorder classically defined as the simultaneous or sequential presence of autoimmune haemolytic anaemia and immune thrombocytopenia, but it has also been described as the presence of at least two autoimmune cytopenias. Recent reports have shown that ES is oft...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.869033/full |
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| author | Maurizio Miano Daniela Guardo Alice Grossi Elena Palmisani Francesca Fioredda Paola Terranova Enrico Cappelli Michela Lupia Monica Traverso Gianluca Dell’Orso Fabio Corsolini Andrea Beccaria Marina Lanciotti Isabella Ceccherini Carlo Dufour |
| author_facet | Maurizio Miano Daniela Guardo Alice Grossi Elena Palmisani Francesca Fioredda Paola Terranova Enrico Cappelli Michela Lupia Monica Traverso Gianluca Dell’Orso Fabio Corsolini Andrea Beccaria Marina Lanciotti Isabella Ceccherini Carlo Dufour |
| author_sort | Maurizio Miano |
| collection | DOAJ |
| description | BackgroundEvans syndrome (ES) is a rare disorder classically defined as the simultaneous or sequential presence of autoimmune haemolytic anaemia and immune thrombocytopenia, but it has also been described as the presence of at least two autoimmune cytopenias. Recent reports have shown that ES is often a manifestation of an underlying inborn error of immunity (IEI) that can benefit from specific treatments.AimsThe aim of this study is to investigate the clinical and immunological characteristics and the underlying genetic background of a single-centre cohort of patients with ES.MethodsData were obtained from a retrospective chart review of patients with a diagnosis of ES followed in our centre. Genetic studies were performed with NGS analysis of 315 genes related to both haematological and immunological disorders, in particular IEI.ResultsBetween 1985 and 2020, 40 patients (23 men, 17 women) with a median age at onset of 6 years (range 0–16) were studied. ES was concomitant and sequential in 18 (45%) and 22 (55%) patients, respectively. Nine of the 40 (8%) patients had a positive family history of autoimmunity. Other abnormal immunological features and signs of lymphoproliferation were present in 24/40 (60%) and 27/40 (67%) of cases, respectively. Seventeen out of 40 (42%) children fit the ALPS diagnostic criteria. The remaining 21 (42%) and 2 (5%) were classified as having an ALPS-like and an idiopathic disease, respectively. Eighteen patients (45%) were found to have an underlying genetic defect on genes FAS, CASP10, TNFSF13B, LRBA, CTLA4, STAT3, IKBGK, CARD11, ADA2, and LIG4. No significant differences were noted between patients with or without variant and between subjects with classical ES and the ones with other forms of multilineage cytopenias.ConclusionsThis study shows that nearly half of patients with ES have a genetic background being in most cases secondary to IEI, and therefore, a molecular evaluation should be offered to all patients. |
| first_indexed | 2024-12-12T02:47:37Z |
| format | Article |
| id | doaj.art-6c959308b41d4cab9b865c7c7100a1b3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T02:47:37Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6c959308b41d4cab9b865c7c7100a1b32022-12-22T00:40:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.869033869033Underlying Inborn Errors of Immunity in Patients With Evans Syndrome and Multilineage Cytopenias: A Single-Centre AnalysisMaurizio Miano0Daniela Guardo1Alice Grossi2Elena Palmisani3Francesca Fioredda4Paola Terranova5Enrico Cappelli6Michela Lupia7Monica Traverso8Gianluca Dell’Orso9Fabio Corsolini10Andrea Beccaria11Marina Lanciotti12Isabella Ceccherini13Carlo Dufour14Hematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyHematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyUnità Operativa Semplice DIpartimentale (UOSD) Genetics and Genomics of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, ItalyHematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyHematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyHematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyHematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyHematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyPediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, University of Genoa, Genoa, ItalyStem Cell Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyLaboratory of Molecular Genetics and Biobanks, IRCCS Istituto Giannina Gaslini, Genoa, ItalyHematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyHematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyUnità Operativa Semplice DIpartimentale (UOSD) Genetics and Genomics of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, ItalyHematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyBackgroundEvans syndrome (ES) is a rare disorder classically defined as the simultaneous or sequential presence of autoimmune haemolytic anaemia and immune thrombocytopenia, but it has also been described as the presence of at least two autoimmune cytopenias. Recent reports have shown that ES is often a manifestation of an underlying inborn error of immunity (IEI) that can benefit from specific treatments.AimsThe aim of this study is to investigate the clinical and immunological characteristics and the underlying genetic background of a single-centre cohort of patients with ES.MethodsData were obtained from a retrospective chart review of patients with a diagnosis of ES followed in our centre. Genetic studies were performed with NGS analysis of 315 genes related to both haematological and immunological disorders, in particular IEI.ResultsBetween 1985 and 2020, 40 patients (23 men, 17 women) with a median age at onset of 6 years (range 0–16) were studied. ES was concomitant and sequential in 18 (45%) and 22 (55%) patients, respectively. Nine of the 40 (8%) patients had a positive family history of autoimmunity. Other abnormal immunological features and signs of lymphoproliferation were present in 24/40 (60%) and 27/40 (67%) of cases, respectively. Seventeen out of 40 (42%) children fit the ALPS diagnostic criteria. The remaining 21 (42%) and 2 (5%) were classified as having an ALPS-like and an idiopathic disease, respectively. Eighteen patients (45%) were found to have an underlying genetic defect on genes FAS, CASP10, TNFSF13B, LRBA, CTLA4, STAT3, IKBGK, CARD11, ADA2, and LIG4. No significant differences were noted between patients with or without variant and between subjects with classical ES and the ones with other forms of multilineage cytopenias.ConclusionsThis study shows that nearly half of patients with ES have a genetic background being in most cases secondary to IEI, and therefore, a molecular evaluation should be offered to all patients.https://www.frontiersin.org/articles/10.3389/fimmu.2022.869033/fullEvans syndromeautoimmune cytopeniasinborn errors of immunity (IEI)immune dysregulationautoimmune haemolytic anaemia (AIHA)ITP (idiopathic thrombocytopenic purpura) |
| spellingShingle | Maurizio Miano Daniela Guardo Alice Grossi Elena Palmisani Francesca Fioredda Paola Terranova Enrico Cappelli Michela Lupia Monica Traverso Gianluca Dell’Orso Fabio Corsolini Andrea Beccaria Marina Lanciotti Isabella Ceccherini Carlo Dufour Underlying Inborn Errors of Immunity in Patients With Evans Syndrome and Multilineage Cytopenias: A Single-Centre Analysis Frontiers in Immunology Evans syndrome autoimmune cytopenias inborn errors of immunity (IEI) immune dysregulation autoimmune haemolytic anaemia (AIHA) ITP (idiopathic thrombocytopenic purpura) |
| title | Underlying Inborn Errors of Immunity in Patients With Evans Syndrome and Multilineage Cytopenias: A Single-Centre Analysis |
| title_full | Underlying Inborn Errors of Immunity in Patients With Evans Syndrome and Multilineage Cytopenias: A Single-Centre Analysis |
| title_fullStr | Underlying Inborn Errors of Immunity in Patients With Evans Syndrome and Multilineage Cytopenias: A Single-Centre Analysis |
| title_full_unstemmed | Underlying Inborn Errors of Immunity in Patients With Evans Syndrome and Multilineage Cytopenias: A Single-Centre Analysis |
| title_short | Underlying Inborn Errors of Immunity in Patients With Evans Syndrome and Multilineage Cytopenias: A Single-Centre Analysis |
| title_sort | underlying inborn errors of immunity in patients with evans syndrome and multilineage cytopenias a single centre analysis |
| topic | Evans syndrome autoimmune cytopenias inborn errors of immunity (IEI) immune dysregulation autoimmune haemolytic anaemia (AIHA) ITP (idiopathic thrombocytopenic purpura) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.869033/full |
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