{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Johnson MB"],"funding":["NCATS NIH HHS","NIDDK NIH HHS","NCRR NIH HHS","NIAID NIH HHS","Diabetes UK","Wellcome Trust","NIH HHS"],"pagination":["e20231704"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11032109"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["221(6)"],"pubmed_abstract":["We previously reported two siblings with inherited PD-1 deficiency who died from autoimmune pneumonitis at 3 and 11 years of age after developing other autoimmune manifestations, including type 1 diabetes (T1D). We report here two siblings, aged 10 and 11 years, with neonatal-onset T1D (diagnosed at the ages of 1 day and 7 wk), who are homozygous for a splice-site variant of CD274 (encoding PD-L1). This variant results in the exclusive expression of an alternative, loss-of-function PD-L1 protein isoform in overexpression experiments and in the patients' primary leukocytes. Surprisingly, cytometric immunophenotyping and single-cell RNA sequencing analysis on blood leukocytes showed largely normal development and transcriptional profiles across lymphoid and myeloid subsets in the PD-L1-defic"],"journal":["The Journal of experimental medicine"],"pubmed_title":["Human inherited PD-L1 deficiency is clinically and immunologically less severe than PD-1 deficiency."],"pmcid":["PMC11032109"],"funding_grant_id":["R01 AI095983","K12 DK133995","UL1TR001866","U19 AI142737","UL1 TR001866","098395/Z/12/Z","16/0005529","U19 AI162568"],"pubmed_authors":["Ogishi M","Quandt Z","Tree TI","Williams E","Hagopian W","Benson B","Speake C","Seeleuthner Y","Roep BO","Wakeling MN","Caswell R","Zhang P","Fagniez I","Johnson MB","Anderson MS","Oram RA","Domingo-Vila C","Resnick B","Russ-Silsby J","Rinchai D","Smithmyer ME","De Franco E","Casanova JL","Boisson-Dupuis S","Hudson M","Weedon MN","EXE-T1D consortium","Hattersley AT","Dufort MJ","Galao RP","Dobbs R","Imane Z"],"additional_accession":[]},"is_claimable":false,"name":"Human inherited PD-L1 deficiency is clinically and immunologically less severe than PD-1 deficiency.","description":"We previously reported two siblings with inherited PD-1 deficiency who died from autoimmune pneumonitis at 3 and 11 years of age after developing other autoimmune manifestations, including type 1 diabetes (T1D). We report here two siblings, aged 10 and 11 years, with neonatal-onset T1D (diagnosed at the ages of 1 day and 7 wk), who are homozygous for a splice-site variant of CD274 (encoding PD-L1). This variant results in the exclusive expression of an alternative, loss-of-function PD-L1 protein isoform in overexpression experiments and in the patients' primary leukocytes. Surprisingly, cytometric immunophenotyping and single-cell RNA sequencing analysis on blood leukocytes showed largely normal development and transcriptional profiles across lymphoid and myeloid subsets in the PD-L1-defic","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jun","modification":"2026-05-29T11:26:19.158Z","creation":"2026-04-08T04:28:27.6Z"},"accession":"S-EPMC11032109","cross_references":{"pubmed":["38634869"],"doi":["10.1084/jem.20231704"]}}