Immune cytopenias as a continuum in inborn errors of immunity: An in‐depth clinical and immunological exploration
Abstract Background Immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN) are disorders characterized by immune‐mediated destruction of hematopoietic cell lineages. A link between pediatric immune cytopenias and inborn errors of immunity (IEI) was establ...
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| Format: | Article |
| Language: | English |
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Wiley
2021-06-01
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| Series: | Immunity, Inflammation and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/iid3.420 |
| _version_ | 1797831435131813888 |
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| author | Daniele Zama Francesca Conti Mattia Moratti Maria E. Cantarini Elena Facchini Beatrice Rivalta Roberto Rondelli Arcangelo Prete Simona Ferrari Marco Seri Andrea Pession |
| author_facet | Daniele Zama Francesca Conti Mattia Moratti Maria E. Cantarini Elena Facchini Beatrice Rivalta Roberto Rondelli Arcangelo Prete Simona Ferrari Marco Seri Andrea Pession |
| author_sort | Daniele Zama |
| collection | DOAJ |
| description | Abstract Background Immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN) are disorders characterized by immune‐mediated destruction of hematopoietic cell lineages. A link between pediatric immune cytopenias and inborn errors of immunity (IEI) was established in particular in the combined and chronic forms. Objective Aim of this study is to provide clinical‐immunological parameters to hematologists useful for a prompt identification of children with immune cytopenias deserving a deeper immunological and genetic evaluation. Methods We retrospectively collected 47 pediatric patients with at least one hematological disorder among which persistent/chronic ITP, AIHA, and AIN, aged 0–18 years at onset of immune cytopenias and/or immune‐dysregulation. The cohort was divided into two groups (IEI+ and IEI−), based on the presence/absence of underlying IEI diagnosis. IEI+ group, formed by 19/47 individuals, included: common variable immune deficiency (CVID; 9/19), autoimmune lymphoproliferative syndrome (ALPS; 4/19), DiGeorge syndrome (1/19), and unclassified IEI (5/19). Results IEI prevalence among patients with ITP, AIHA, AIN, and Evans Syndrome was respectively of 42%, 64%, 36%, and 62%. In IEI+ group the extended immunophenotyping identified the presence of statistically significant (p < .05) specific characteristics, namely T/B lymphopenia, decrease in naїve T‐cells%, switched memory B‐cells%, plasmablasts%, and/or immunoglobulins, increase in effector/central memory T‐cells% and CD21low B‐cells%. Except for DiGeorge and three ALPS patients, only 2/9 CVID patients had a molecular diagnosis for IEI: one carrying the pathogenic variant CR2:c.826delT, the likely pathogenic variant PRF1:c.272C> and the compound heterozygous TNFRSF13B variants p.Ser144Ter (pathogenic) and p.Cys193Arg (variant of uncertain significance), the other one carrying the likely pathogenic monoallelic variant TNFRSF13B:p.Ile87Asn. Conclusion The synergy between hematologists and immunologists can improve and fasten diagnosis and management of patients with immune cytopenias through a wide focused clinical/immunophenotypical characterization, which identifies children worthy of IEI‐related molecular analysis, favouring a genetic IEI diagnosis and potentially unveiling new targeted‐gene variants responsible for IEI phenotype. |
| first_indexed | 2024-04-09T13:52:48Z |
| format | Article |
| id | doaj.art-cd52cfda79294331b3b66bf3fd4789dd |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-04-09T13:52:48Z |
| publishDate | 2021-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-cd52cfda79294331b3b66bf3fd4789dd2023-05-08T13:20:48ZengWileyImmunity, Inflammation and Disease2050-45272021-06-019258359410.1002/iid3.420Immune cytopenias as a continuum in inborn errors of immunity: An in‐depth clinical and immunological explorationDaniele Zama0Francesca Conti1Mattia Moratti2Maria E. Cantarini3Elena Facchini4Beatrice Rivalta5Roberto Rondelli6Arcangelo Prete7Simona Ferrari8Marco Seri9Andrea Pession10Pediatric Unit IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna ItalyPediatric Unit IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna ItalyPediatric Unit IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna ItalyPediatric Unit IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna ItalyPediatric Unit IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna ItalyPediatric Unit IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna ItalyPediatric Unit IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna ItalyPediatric Unit IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna ItalyPediatric Unit IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna ItalyPediatric Unit IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna ItalyPediatric Unit IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna ItalyAbstract Background Immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN) are disorders characterized by immune‐mediated destruction of hematopoietic cell lineages. A link between pediatric immune cytopenias and inborn errors of immunity (IEI) was established in particular in the combined and chronic forms. Objective Aim of this study is to provide clinical‐immunological parameters to hematologists useful for a prompt identification of children with immune cytopenias deserving a deeper immunological and genetic evaluation. Methods We retrospectively collected 47 pediatric patients with at least one hematological disorder among which persistent/chronic ITP, AIHA, and AIN, aged 0–18 years at onset of immune cytopenias and/or immune‐dysregulation. The cohort was divided into two groups (IEI+ and IEI−), based on the presence/absence of underlying IEI diagnosis. IEI+ group, formed by 19/47 individuals, included: common variable immune deficiency (CVID; 9/19), autoimmune lymphoproliferative syndrome (ALPS; 4/19), DiGeorge syndrome (1/19), and unclassified IEI (5/19). Results IEI prevalence among patients with ITP, AIHA, AIN, and Evans Syndrome was respectively of 42%, 64%, 36%, and 62%. In IEI+ group the extended immunophenotyping identified the presence of statistically significant (p < .05) specific characteristics, namely T/B lymphopenia, decrease in naїve T‐cells%, switched memory B‐cells%, plasmablasts%, and/or immunoglobulins, increase in effector/central memory T‐cells% and CD21low B‐cells%. Except for DiGeorge and three ALPS patients, only 2/9 CVID patients had a molecular diagnosis for IEI: one carrying the pathogenic variant CR2:c.826delT, the likely pathogenic variant PRF1:c.272C> and the compound heterozygous TNFRSF13B variants p.Ser144Ter (pathogenic) and p.Cys193Arg (variant of uncertain significance), the other one carrying the likely pathogenic monoallelic variant TNFRSF13B:p.Ile87Asn. Conclusion The synergy between hematologists and immunologists can improve and fasten diagnosis and management of patients with immune cytopenias through a wide focused clinical/immunophenotypical characterization, which identifies children worthy of IEI‐related molecular analysis, favouring a genetic IEI diagnosis and potentially unveiling new targeted‐gene variants responsible for IEI phenotype.https://doi.org/10.1002/iid3.420autoimmune hemolytic anemiaautoimmune lymphoproliferative syndromeautoimmune neutropeniacommon variable immune deficiencyDiGeorge syndromeimmune cytopenias |
| spellingShingle | Daniele Zama Francesca Conti Mattia Moratti Maria E. Cantarini Elena Facchini Beatrice Rivalta Roberto Rondelli Arcangelo Prete Simona Ferrari Marco Seri Andrea Pession Immune cytopenias as a continuum in inborn errors of immunity: An in‐depth clinical and immunological exploration Immunity, Inflammation and Disease autoimmune hemolytic anemia autoimmune lymphoproliferative syndrome autoimmune neutropenia common variable immune deficiency DiGeorge syndrome immune cytopenias |
| title | Immune cytopenias as a continuum in inborn errors of immunity: An in‐depth clinical and immunological exploration |
| title_full | Immune cytopenias as a continuum in inborn errors of immunity: An in‐depth clinical and immunological exploration |
| title_fullStr | Immune cytopenias as a continuum in inborn errors of immunity: An in‐depth clinical and immunological exploration |
| title_full_unstemmed | Immune cytopenias as a continuum in inborn errors of immunity: An in‐depth clinical and immunological exploration |
| title_short | Immune cytopenias as a continuum in inborn errors of immunity: An in‐depth clinical and immunological exploration |
| title_sort | immune cytopenias as a continuum in inborn errors of immunity an in depth clinical and immunological exploration |
| topic | autoimmune hemolytic anemia autoimmune lymphoproliferative syndrome autoimmune neutropenia common variable immune deficiency DiGeorge syndrome immune cytopenias |
| url | https://doi.org/10.1002/iid3.420 |
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