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Review
. 2023 Feb;43(2):247-270.
doi: 10.1007/s10875-022-01418-y. Epub 2023 Jan 17.

Clinical Practice Guidelines for the Immunological Management of Chromosome 22q11.2 Deletion Syndrome and Other Defects in Thymic Development

Peter J Mustillo  1 , Kathleen E Sullivan  2 , Ivan K Chinn  3 , Luigi D Notarangelo  4 , Elie Haddad  5 , E Graham Davies  6 , Maria Teresa de la Morena  7 , Nicholas Hartog  8 , Joyce E Yu  9 , Vivian P Hernandez-Trujillo  10 , Winnie Ip  11 , Jose Franco  12 , Eleonora Gambineri  13   14 , Scott E Hickey  15 , Elizabeth Varga  16 , M Louise Markert  17
Affiliations
Review

Clinical Practice Guidelines for the Immunological Management of Chromosome 22q11.2 Deletion Syndrome and Other Defects in Thymic Development

Peter J Mustillo et al. J Clin Immunol. 2023 Feb.

Erratum in

Abstract

Current practices vary widely regarding the immunological work-up and management of patients affected with defects in thymic development (DTD), which include chromosome 22q11.2 microdeletion syndrome (22q11.2del) and other causes of DiGeorge syndrome (DGS) and coloboma, heart defect, atresia choanae, retardation of growth and development, genital hypoplasia, ear anomalies/deafness (CHARGE) syndrome. Practice variations affect the initial and subsequent assessment of immune function, the terminology used to describe the condition and immune status, the accepted criteria for recommending live vaccines, and how often follow-up is needed based on the degree of immune compromise. The lack of consensus and widely varying practices highlight the need to establish updated immunological clinical practice guidelines. These guideline recommendations provide a comprehensive review for immunologists and other clinicians who manage immune aspects of this group of disorders.

Keywords: 22q11.2 deletion; CHARGE syndrome; Defects in thymic development; DiGeorge syndrome; Immunology guidelines; Thymic implant.

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Conflict of interest statement

PJM received past honoraria from Horizon Therapeutics (advisory board). KS serves on the Immune Deficiency Foundation. The thymic transplant description and other references of MLM relate to the work that that was funded, in part, by Enzyant Therapeutics or performed under a Sponsored Research Agreement in partnership with Enzyvant Therapeutics, GmbH. IKC reports work with Wolters Kluwer (UptoDate), past consultant for Enzyvant. NH reports COI with Horizon, speaker, advisory board; Binding Site, speaker; Takeda, speaker, advisory board; and Pharming Healthcare, advisory board, scientific steering committee. EH is a recipient of honoraria for AdBoard meetings from CSl-Behring, Octapharma, and Takeda and from DSMB from Jasper Therapeutics and owns shares in Immugenia biotech company. The other authors declare they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Chromosomal deletions in the 22q11.2 region. Credit Rozas MF, Benavides F, Leon L, Repetto GM. Orphanet J of Rare Dis https://doi.org/10.1186/s13023-019-1170-x
Fig. 2
Fig. 2
Depiction of how CD45RA may be re-expressed (highlighted in figure) despite not representing a truly naïve T lymphocyte. Unlike TEMRA cells, true naïve recent thymic emigrant T cells express CD31 and CCR7 surface markers. Gated from CD45+CD3+ T cells expressing either CD4 or CD8. CCR7, chemokine receptor 7; PD1, programmed death 1; LKRG1, killer lectin inhibitory receptor 1; TCM, T central memory; TEMRA, T effector memory re-expressing CD45RA; TEM, T effector memory. Figure created using BioRender.com
See this image and copyright information in PMC

References

    1. Kelley RI, Zackai EH, Emanuel BS, Kistenmacher M, Greenberg F, Punnett HH. The association of the DiGeorge anomalad with partial monosomy of chromosome 22. J Pediatr. 1982;101(2):197–200. doi: 10.1016/S0022-3476(82)80116-9. - DOI - PubMed
    1. Sullivan KE. Chromosome 22q11.2 deletion syndrome: DiGeorge syndrome/velocardiofacial Syndrome. Immunol Allergy Clin North Am. 2008;28(2):353–66. doi: 10.1016/j.iac.2008.01.003. - DOI - PubMed
    1. Bartsch O, Wagner A, Hinkel GK, Lichtner P, Murken J, Schuffenhauer S. No evidence for chromosomal microdeletions at the second DiGeorge syndrome locus on 10p near D10S585. Am J Med Genet. 1999;83(5):425–426. doi: 10.1002/(SICI)1096-8628(19990423)83:5<425::AID-AJMG17>3.0.CO;2-Q. - DOI - PubMed
    1. Gennery AR. Immunological aspects of 22q11.2 deletion syndrome. Cell Mol Life Sci. 2012;69(1):17–27. doi: 10.1007/s00018-011-0842-z. - DOI - PMC - PubMed
    1. Yagi H, Furutani Y, Hamada H, Sasaki T, Asakawa S, Minoshima S, et al. Role of TBX1 in human del22q112 syndrome. The Lancet. 2003;362(9393):1366–73. doi: 10.1016/S0140-6736(03)14632-6. - DOI - PubMed