Circulating Follicular Helper and Follicular Regulatory T Cells Are Severely Compromised in Human CD40 Deficiency: A Case Report

Maria Pia Cicalese, Jolanda Gerosa, Manuela Baronio, Davide Montin, Francesco Licciardi, Annarosa Soresina, Rosa Maria Dellepiane, Maurizio Miano, Lucia Augusta Baselli, Stefano Volpi, Carlo Dufour, Alessandro Plebani, Alessandro Aiuti, Vassilios Lougaris, Georgia Fousteri

Research output: Contribution to journalArticle

Abstract

Mutations in genes that control class switch recombination and somatic hypermutation during the germinal center (GC) response can cause diverse immune dysfunctions. In particular, mutations in CD40LG, CD40, AICDA, or UNG cause hyper-IgM (HIGM) syndrome, a heterogeneous group of primary immunodeficiencies. Follicular helper (Tfh) and follicular regulatory (Tfr) T cells play a key role in the formation and regulation of GCs, but their role in HIGM pathogenesis is still limited. Here, we found that compared to CD40 ligand (CD40L)- and activation-induced cytidine deaminase (AICDA)-deficient patients, circulating Tfh and Tfr cells were severely compromised in terms of frequency and activation phenotype in a child with CD40 deficiency. These findings offer useful insight for human Tfh biology, with potential implications for understanding the molecular basis of HIGM syndrome caused by mutations in CD40.

Original languageEnglish
Pages (from-to)1761
JournalFrontiers in Immunology
Volume9
DOIs
Publication statusPublished - 2018

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Hyper-IgM Immunodeficiency Syndrome
Regulatory T-Lymphocytes
Mutation
CD40 Ligand
Germinal Center
Genetic Recombination
Immunoglobulin M
Phenotype
Genes
AICDA (activation-induced cytidine deaminase)

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Circulating Follicular Helper and Follicular Regulatory T Cells Are Severely Compromised in Human CD40 Deficiency : A Case Report. / Cicalese, Maria Pia; Gerosa, Jolanda; Baronio, Manuela; Montin, Davide; Licciardi, Francesco; Soresina, Annarosa; Dellepiane, Rosa Maria; Miano, Maurizio; Baselli, Lucia Augusta; Volpi, Stefano; Dufour, Carlo; Plebani, Alessandro; Aiuti, Alessandro; Lougaris, Vassilios; Fousteri, Georgia.

In: Frontiers in Immunology, Vol. 9, 2018, p. 1761.

Research output: Contribution to journalArticle

Cicalese, Maria Pia ; Gerosa, Jolanda ; Baronio, Manuela ; Montin, Davide ; Licciardi, Francesco ; Soresina, Annarosa ; Dellepiane, Rosa Maria ; Miano, Maurizio ; Baselli, Lucia Augusta ; Volpi, Stefano ; Dufour, Carlo ; Plebani, Alessandro ; Aiuti, Alessandro ; Lougaris, Vassilios ; Fousteri, Georgia. / Circulating Follicular Helper and Follicular Regulatory T Cells Are Severely Compromised in Human CD40 Deficiency : A Case Report. In: Frontiers in Immunology. 2018 ; Vol. 9. pp. 1761.
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abstract = "Mutations in genes that control class switch recombination and somatic hypermutation during the germinal center (GC) response can cause diverse immune dysfunctions. In particular, mutations in CD40LG, CD40, AICDA, or UNG cause hyper-IgM (HIGM) syndrome, a heterogeneous group of primary immunodeficiencies. Follicular helper (Tfh) and follicular regulatory (Tfr) T cells play a key role in the formation and regulation of GCs, but their role in HIGM pathogenesis is still limited. Here, we found that compared to CD40 ligand (CD40L)- and activation-induced cytidine deaminase (AICDA)-deficient patients, circulating Tfh and Tfr cells were severely compromised in terms of frequency and activation phenotype in a child with CD40 deficiency. These findings offer useful insight for human Tfh biology, with potential implications for understanding the molecular basis of HIGM syndrome caused by mutations in CD40.",
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AU - Cicalese, Maria Pia

AU - Gerosa, Jolanda

AU - Baronio, Manuela

AU - Montin, Davide

AU - Licciardi, Francesco

AU - Soresina, Annarosa

AU - Dellepiane, Rosa Maria

AU - Miano, Maurizio

AU - Baselli, Lucia Augusta

AU - Volpi, Stefano

AU - Dufour, Carlo

AU - Plebani, Alessandro

AU - Aiuti, Alessandro

AU - Lougaris, Vassilios

AU - Fousteri, Georgia

PY - 2018

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AB - Mutations in genes that control class switch recombination and somatic hypermutation during the germinal center (GC) response can cause diverse immune dysfunctions. In particular, mutations in CD40LG, CD40, AICDA, or UNG cause hyper-IgM (HIGM) syndrome, a heterogeneous group of primary immunodeficiencies. Follicular helper (Tfh) and follicular regulatory (Tfr) T cells play a key role in the formation and regulation of GCs, but their role in HIGM pathogenesis is still limited. Here, we found that compared to CD40 ligand (CD40L)- and activation-induced cytidine deaminase (AICDA)-deficient patients, circulating Tfh and Tfr cells were severely compromised in terms of frequency and activation phenotype in a child with CD40 deficiency. These findings offer useful insight for human Tfh biology, with potential implications for understanding the molecular basis of HIGM syndrome caused by mutations in CD40.

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