biostudies-literatureUnknown52(7)Milardi GCommon variable immunodeficiency (CVID) is the most frequent primary antibody deficiency whereby follicular helper T (Tfh) cells fail to establish productive responses with B cells in germinal centers. Here, we analyzed the frequency, phenotype, transcriptome, and function of circulating Tfh (cTfh) cells in CVID patients displaying autoimmunity as an additional phenotype. A group of patients showed a high frequency of cTfh1 cells and a prominent expression of PD-1 and ICOS as well as a cTfh mRNA signature consistent with highly activated, but exhausted, senescent, and apoptotic cells. Plasmatic CXCL13 levels were elevated in this group and positively correlated with cTfh1 cell frequency and PD-1 levels. Monoallelic variants in RTEL1, a telomere length- and DNA repair-related gene, were ideEuropean journal of immunology1171-1189https://www.ebi.ac.uk/biostudies/studies/S-EPMC9542315biostudies-literatureFollicular helper T cell signature of replicative exhaustion, apoptosis, and senescence in common variable immunodeficiency.PMC9542315De Pellegrin MRovere-Querini PBongiovanni LChetta AAVacca ABarzaghi FPacillo LJofra TDi Micco RGiancotta CGerosa JMatarese APiemonti LMelzi RBrigida IPlebani ANano RPiemontese SRomano FTrimarchi MDarin SMarinoni MCirillo EDi Lorenzo BCicalese MPZoccolillo MMerelli ICancrini CPonzoni MMilardi GOmrani MSpecchia FLougaris VMontin DFilippini MDi Matteo GGiardino GAiuti APignata CConti AMarktel SPetrovas CAssanelli AFousteri GLaurenzi ADanieli MGDi Cesare SDionisio FDellepiane RMBarcella MSordi VAzzari CFerrua FPozzo Giuffrida FfalseFollicular helper T cell signature of replicative exhaustion, apoptosis, and senescence in common variable immunodeficiency.Common variable immunodeficiency (CVID) is the most frequent primary antibody deficiency whereby follicular helper T (Tfh) cells fail to establish productive responses with B cells in germinal centers. Here, we analyzed the frequency, phenotype, transcriptome, and function of circulating Tfh (cTfh) cells in CVID patients displaying autoimmunity as an additional phenotype. A group of patients showed a high frequency of cTfh1 cells and a prominent expression of PD-1 and ICOS as well as a cTfh mRNA signature consistent with highly activated, but exhausted, senescent, and apoptotic cells. Plasmatic CXCL13 levels were elevated in this group and positively correlated with cTfh1 cell frequency and PD-1 levels. Monoallelic variants in RTEL1, a telomere length- and DNA repair-related gene, were ide2022-01-01T00:00:00Z2022 Jul2025-04-19T04:49:07.722Z2025-04-19T04:49:07.722ZS-EPMC95423153556284910.1002/eji.202149480