Clinical and Treatment History of Patients with Partial DiGeorge Syndrome and Autoimmune Cytopenia at Multiple Centers.

Autoimmune cytopenia Immune dysregulation Partial DiGeorge syndrome

Journal

Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137

Informations de publication

Date de publication:
17 Jan 2024
Historique:
received: 09 06 2023
accepted: 05 10 2023
medline: 17 1 2024
pubmed: 17 1 2024
entrez: 17 1 2024
Statut: epublish

Résumé

Patients with partial DiGeorge syndrome (pDGS) can present with immune dysregulation, the most common being autoimmune cytopenia (AIC). There is a lack of consensus on the approach to type, combination, and timing of therapies for AIC in pDGS. Recognition of immune dysregulation early in pDGS clinical course may help individualize treatment and prevent adverse outcomes from chronic immune dysregulation. Objectives of this study were to characterize the natural history, immune phenotype, and biomarkers in pDGS with AIC. Data on clinical presentation, disease severity, immunological phenotype, treatment selection, and response for patients with pDGS with AIC were collected via retrospective chart review. Flow cytometric analysis was done to assess T and B cell subsets, including biomarkers of immune dysregulation. Twenty-nine patients with the diagnosis of pDGS and AIC were identified from 5 international institutions. Nineteen (62%) patients developed Evan's syndrome (ES) during their clinical course and twenty (69%) had antibody deficiency syndrome. These patients demonstrated expansion in T follicular helper cells, CD19 AIC in pDGS is often refractory to conventional AIC treatment paradigms. Biomarkers may have utility for correlation with disease state and potentially even response to therapy. Immunomodulating therapies could be initiated early based on early immune phenotyping and biomarkers before the disease develops or significantly worsens.

Sections du résumé

BACKGROUND BACKGROUND
Patients with partial DiGeorge syndrome (pDGS) can present with immune dysregulation, the most common being autoimmune cytopenia (AIC). There is a lack of consensus on the approach to type, combination, and timing of therapies for AIC in pDGS. Recognition of immune dysregulation early in pDGS clinical course may help individualize treatment and prevent adverse outcomes from chronic immune dysregulation.
OBJECTIVES OBJECTIVE
Objectives of this study were to characterize the natural history, immune phenotype, and biomarkers in pDGS with AIC.
METHODS METHODS
Data on clinical presentation, disease severity, immunological phenotype, treatment selection, and response for patients with pDGS with AIC were collected via retrospective chart review. Flow cytometric analysis was done to assess T and B cell subsets, including biomarkers of immune dysregulation.
RESULTS RESULTS
Twenty-nine patients with the diagnosis of pDGS and AIC were identified from 5 international institutions. Nineteen (62%) patients developed Evan's syndrome (ES) during their clinical course and twenty (69%) had antibody deficiency syndrome. These patients demonstrated expansion in T follicular helper cells, CD19
CONCLUSIONS CONCLUSIONS
AIC in pDGS is often refractory to conventional AIC treatment paradigms. Biomarkers may have utility for correlation with disease state and potentially even response to therapy. Immunomodulating therapies could be initiated early based on early immune phenotyping and biomarkers before the disease develops or significantly worsens.

Identifiants

DOI: 10.1007/s10875-023-01607-3 PMID: 38231436
pubmed: 38231436
doi: 10.1007/s10875-023-01607-3
pii: 10.1007/s10875-023-01607-3
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

42

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Références

McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore). 2011;90(1):1–18.
doi: 10.1097/MD.0b013e3182060469 pubmed: 21200182
Sullivan KE. Chromosome 22q11.2 deletion syndrome and DiGeorge syndrome. Immunol Rev. 2019;287(1):186–201.
doi: 10.1111/imr.12701 pubmed: 30565249
Seidel MG. Autoimmune and other cytopenias in primary immunodeficiencies: pathomechanisms, novel differential diagnoses, and treatment. Blood. 2014;124(15):2337–44.
doi: 10.1182/blood-2014-06-583260 pubmed: 25163701 pmcid: 4192747
Benn P, et al. Pediatric healthcare costs for patients with 22q11.2 deletion syndrome. Mol Genet Genomic Med. 2017;5(6):631–8.
doi: 10.1002/mgg3.310 pubmed: 29178641 pmcid: 6234953
Gennery AR, et al. Antibody deficiency and autoimmunity in 22q11.2 deletion syndrome. Arch Dis Child. 2002;86(6):422–5.
doi: 10.1136/adc.86.6.422 pubmed: 12023174 pmcid: 1763000
Teachey DT, Lambert MP. Diagnosis and management of autoimmune cytopenias in childhood. Pediatr Clin North Am. 2013;60(6):1489–511.
doi: 10.1016/j.pcl.2013.08.009 pubmed: 24237984 pmcid: 5384653
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap) - a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81.
doi: 10.1016/j.jbi.2008.08.010 pubmed: 18929686
Westermann-Clark E, et al. Primary immunodeficiency in children with autoimmune cytopenias: retrospective 154-patient cohort. Front Immunol. 2021;12:649182.
doi: 10.3389/fimmu.2021.649182 pubmed: 33968040 pmcid: 8100326
Thalhammer J, et al. Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations. J Allergy Clin Immunol. 2021;148(5):1332-1341e5.
doi: 10.1016/j.jaci.2021.04.015 pubmed: 33895260
Montin D, et al. Immunophenotype anomalies predict the development of autoimmune cytopenia in 22q11.2 deletion syndrome. J Allergy Clin Immunol Pract. 2019;7(7):2369–76.
doi: 10.1016/j.jaip.2019.03.014 pubmed: 30922987
Giardino G, et al. Clinical and immunological features in a cohort of patients with partial DiGeorge syndrome followed at a single center. Blood. 2019;133(24):2586–96.
doi: 10.1182/blood.2018885244 pubmed: 31015189
Hadjadj J, et al. Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes. Blood. 2019;134(1):9–21.
doi: 10.1182/blood-2018-11-887141 pubmed: 30940614
Tison BE, et al. Autoimmunity in a cohort of 130 pediatric patients with partial DiGeorge syndrome. J Allergy Clin Immunol. 2011;128(5):1115-71e1-3.
doi: 10.1016/j.jaci.2011.06.043 pubmed: 21835443
Soldatou A, et al. Transient effect of anti-CD20 therapy in a child with 22q11.2 deletion syndrome and severe steroid refractory cytopenias: a case report. J Pediatr Hematol Oncol. 2013;35(4):311–4.
doi: 10.1097/MPH.0b013e31828be602 pubmed: 23612383
Seidel MG. Treatment of immune-mediated cytopenias in patients with primary immunodeficiencies and immune regulatory disorders (PIRDs). Hematol Am Soc Hematol Educ Program. 2020;2020(1):673–9.
doi: 10.1182/hematology.2020000153
Neunert C, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829–66.
doi: 10.1182/bloodadvances.2019000966 pubmed: 31794604 pmcid: 6963252
Neven B, et al. A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation. Blood. 2011;118(18):4798–807.
doi: 10.1182/blood-2011-04-347641 pubmed: 21885602
Martin JR, Pattee CJ. Complications observed during ACTH and cortisone therapy. Can Med Assoc J. 1953;68(2):146–52.
pubmed: 13019733 pmcid: 1822974
Rao VK. Approaches to managing autoimmune cytopenias in novel immunological disorders with genetic underpinnings like autoimmune lymphoproliferative syndrome. Front Pediatr. 2015;3:65.
doi: 10.3389/fped.2015.00065 pubmed: 26258116 pmcid: 4508836
Grimes AB, et al. Refractory autoimmune cytopenias in pediatric Evans syndrome with underlying systemic immune dysregulation. Eur J Haematol. 2021;106(6):783–7.
doi: 10.1111/ejh.13600 pubmed: 33570766
Bride KL, et al. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood. 2016;127(1):17–28.
doi: 10.1182/blood-2015-07-657981 pubmed: 26504182 pmcid: 4705607
Biggs SE, Gilchrist B, May KR. Chromosome 22q11.2 deletion (DiGeorge syndrome): immunologic features, diagnosis, and management. Curr Allergy Asthma Rep. 2023;23(4):213–22.
doi: 10.1007/s11882-023-01071-4 pubmed: 36897497 pmcid: 9999075
Lawrence S, et al. Thrombocytopenia in patients with chromosome 22q11.2 deletion syndrome. J Pediatr. 2003;143(2):277–8.
doi: 10.1067/S0022-3476(03)00248-8 pubmed: 12970648

Auteurs

Priya K Patel (PK)

Johns Hopkins All Children's Hospital, 601 5Th Street South, Outpatient Care Clinic, 3Rd Floor, St. Petersburg, FL, 33701, USA. patelp15@usf.edu.
Department of Pediatrics, Division of Allergy and Immunology, University of South Florida Morsani College of Medicine, St Petersburg, FL, USA. patelp15@usf.edu.
ORCID: 0000-0001-5400-3782

Michell Lozano Chinga (ML)

Division of Pediatric Hematology Oncology, University of Utah Primary Children's Hospital, Salt Lake City, UT, USA.
Division of Immunology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.

Melis Yilmaz (M)

Department of Pediatrics, Division of Allergy and Immunology, University of South Florida Morsani College of Medicine, St Petersburg, FL, USA.

Sonia Joychan (S)

Department of Pediatrics, Division of Allergy and Immunology, University of South Florida Morsani College of Medicine, St Petersburg, FL, USA.

Boglarka Ujhazi (B)

Department of Pediatrics, Division of Allergy and Immunology, University of South Florida Morsani College of Medicine, St Petersburg, FL, USA.

Maryssa Ellison (M)

Department of Pediatrics, Division of Allergy and Immunology, University of South Florida Morsani College of Medicine, St Petersburg, FL, USA.

Sumai Gordon (S)

Department of Pediatrics, Division of Allergy and Immunology, University of South Florida Morsani College of Medicine, St Petersburg, FL, USA.

Daime Nieves (D)

Johns Hopkins All Children's Hospital, 601 5Th Street South, Outpatient Care Clinic, 3Rd Floor, St. Petersburg, FL, 33701, USA.
Department of Pediatrics, Division of Allergy and Immunology, University of South Florida Morsani College of Medicine, St Petersburg, FL, USA.

Krisztian Csomos (K)

Department of Pediatrics, Division of Allergy and Immunology, University of South Florida Morsani College of Medicine, St Petersburg, FL, USA.

Don Eslin (D)

BayCare Medical Group, St. Joseph's Hospital, Pediatric Hematology Oncology, St. Petersburg, FL, USA.

Zeinab A Afify (ZA)

Division of Pediatric Hematology Oncology, University of Utah Primary Children's Hospital, Salt Lake City, UT, USA.

Jessica Meznarich (J)

Division of Pediatric Hematology Oncology, University of Utah Primary Children's Hospital, Salt Lake City, UT, USA.

John Bohnsack (J)

Division of Pediatric Hematology Oncology, University of Utah Primary Children's Hospital, Salt Lake City, UT, USA.

Kelly Walkovich (K)

BayCare Medical Group, St. Joseph's Hospital, Pediatric Hematology Oncology, St. Petersburg, FL, USA.

Markus G Seidel (MG)

Clinical Department of Pediatric Hematology Oncology, Medical University of Graz, Graz, Austria.

Svetlana Sharapova (S)

Belarusian Research Center for Pediatric Oncology, Hematology, and Immunology, Minsk, Belarus.

Oksana Boyarchyk (O)

Immunopathology Department, National Research Center Institute of Immunology FMBA, Moscow, Russia.

Elena Latysheva (E)

Belarusian Research Center for Pediatric Oncology, Hematology, and Immunology, Minsk, Belarus.

Irina Tuzankina (I)

Belarusian Research Center for Pediatric Oncology, Hematology, and Immunology, Minsk, Belarus.

Ahmad B Shaker (AB)

BayCare Medical Group, St. Anthony's Hospital, St. Petersburg, FL, USA.

Irmel Ayala (I)

Johns Hopkins All Children's Hospital, 601 5Th Street South, Outpatient Care Clinic, 3Rd Floor, St. Petersburg, FL, 33701, USA.

Panida Sriaroon (P)

Johns Hopkins All Children's Hospital, 601 5Th Street South, Outpatient Care Clinic, 3Rd Floor, St. Petersburg, FL, 33701, USA.
Department of Pediatrics, Division of Allergy and Immunology, University of South Florida Morsani College of Medicine, St Petersburg, FL, USA.

Emma Westermann-Clark (E)

Department of Pediatrics, Division of Allergy and Immunology, University of South Florida Morsani College of Medicine, St Petersburg, FL, USA.

Jolan E Walter (JE)

Johns Hopkins All Children's Hospital, 601 5Th Street South, Outpatient Care Clinic, 3Rd Floor, St. Petersburg, FL, 33701, USA.
Department of Pediatrics, Division of Allergy and Immunology, University of South Florida Morsani College of Medicine, St Petersburg, FL, USA.

Classifications MeSH