AUTHOR=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 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01761

DOI=10.3389/fimmu.2018.01761

ISSN=1664-3224

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 syndrome (HIGM), 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 CD40L- and AID-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 the understanding of molecular basis of HIGM syndrome caused by mutations in CD40.