Underlying Inborn Errors of Immunity in Patients With Evans Syndrome and Multilineage Cytopenias: A Single-Centre Analysis.
ALPS (autoimmune lymphoproliferative syndrome)
Evans syndrome
ITP (idiopathic thrombocytopenic purpura)
autoimmune cytopenias
autoimmune haemolytic anaemia (AIHA)
autoimmune neutropenia (AIN)
immune dysregulation
inborn errors of immunity (IEI)
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
03
02
2022
accepted:
07
04
2022
entrez:
3
6
2022
pubmed:
4
6
2022
medline:
7
6
2022
Statut:
epublish
Résumé
Evans 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. The 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. Data 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. Between 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 This 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.
Sections du résumé
Background
Evans 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.
Aims
The 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.
Methods
Data 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.
Results
Between 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
Conclusions
This 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.
Identifiants
pubmed: 35655776
doi: 10.3389/fimmu.2022.869033
pmc: PMC9152001
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
LRBA protein, human
EC 2.7.10.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
869033Informations de copyright
Copyright © 2022 Miano, Guardo, Grossi, Palmisani, Fioredda, Terranova, Cappelli, Lupia, Traverso, Dell’Orso, Corsolini, Beccaria, Lanciotti, Ceccherini and Dufour.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Front Pediatr. 2019 Jul 23;7:304
pubmed: 31396497
Curr Opin Pediatr. 2019 Dec;31(6):851-862
pubmed: 31693597
Br J Haematol. 2015 Oct;171(2):247-253
pubmed: 26058843
Blood Transfus. 2018 Jul;16(4):352-357
pubmed: 29757134
Front Pediatr. 2015 Sep 29;3:79
pubmed: 26484337
Br J Haematol. 2019 Nov;187(4):502-508
pubmed: 31309545
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Am J Hematol. 2021 Sep 1;96(9):1077-1086
pubmed: 34000087
Arch Dis Child. 1997 Sep;77(3):245-8
pubmed: 9370906
Front Immunol. 2019 Apr 11;10:316
pubmed: 31031743
Blood. 2015 Jan 22;125(4):591-9
pubmed: 25359994
Br J Haematol. 2016 Feb;172(4):524-34
pubmed: 26625877
Rheumatology (Oxford). 2022 Feb 2;61(2):696-704
pubmed: 33909886
Eur J Haematol. 2021 Jun;106(6):783-787
pubmed: 33570766
Br J Haematol. 2016 Nov;175(3):490-495
pubmed: 27447678
Clin Immunol. 2018 Feb;187:102-103
pubmed: 29104089
J Clin Invest. 2008 Jan;118(1):333-41
pubmed: 18097474
Blood. 2019 Jul 4;134(1):9-21
pubmed: 30940614
Nat Rev Rheumatol. 2017 Dec 19;14(1):7-18
pubmed: 29255211
J Allergy Clin Immunol Pract. 2020 Nov - Dec;8(10):3535-3542
pubmed: 32702516
J Allergy Clin Immunol. 2017 Nov;140(5):1388-1393.e8
pubmed: 28192146
Blood. 2009 Mar 12;113(11):2386-93
pubmed: 19005182
J Pediatr Hematol Oncol. 2021 Nov 1;43(8):e1168-e1172
pubmed: 33625086
Blood. 2016 Jan 7;127(1):17-28
pubmed: 26504182
Blood Adv. 2019 Jun 25;3(12):1897-1906
pubmed: 31235526
Int Rev Immunol. 2015;34(6):445-59
pubmed: 26269396
Hum Mol Genet. 2004 Aug 15;13(16):1763-73
pubmed: 15229184
Expert Rev Clin Immunol. 2019 Oct;15(10):1033-1046
pubmed: 31535575
Pediatr Blood Cancer. 2011 Jul 15;57(1):10-7
pubmed: 21448998
Genes (Basel). 2021 Aug 24;12(9):
pubmed: 34573280
Blood. 2010 Oct 7;116(14):e35-40
pubmed: 20538792
Clin Immunol. 2018 Mar;188:52-57
pubmed: 29330115
J Allergy Clin Immunol Pract. 2016 Nov - Dec;4(6):1089-1100
pubmed: 27836058
Front Pediatr. 2019 Apr 16;7:122
pubmed: 31058115
Br J Haematol. 2019 Mar;184(5):861-864
pubmed: 29527658
Blood Transfus. 2017 May;15(3):259-267
pubmed: 28151390
J Pediatr Hematol Oncol. 1997 Sep-Oct;19(5):433-7
pubmed: 9329465
Front Immunol. 2021 Oct 14;12:754029
pubmed: 34721429
Am J Pediatr Hematol Oncol. 1988 Winter;10(4):330-8
pubmed: 3071168