{"doi":"10.1084/jem.20231704","title":"Human inherited PD-L1 deficiency is clinically and immunologically less severe than PD-1 deficiency.","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-deficient siblings, contrasting with the extensive dysregulation of both lymphoid and myeloid leukocyte compartments in PD-1 deficiency. Our findings suggest that PD-1 and PD-L1 are essential for preventing early-onset T1D but that, unlike PD-1 deficiency, PD-L1 deficiency does not lead to fatal autoimmunity with extensive leukocytic dysregulation.","journal":"PubMed","year":2024,"id":436550,"datarank":0.4515660937289553,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.07883009626075514,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.07883009626075514,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":7,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"is_data_producer":true,"deposit_databanks":{"BioProject":["PRJNA1084900"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":104463,"name":"Masato Ogishi","orcid":"0000-0003-2421-7389","position":1,"is_corresponding":false},{"id":717732,"name":"Clara Domingo‐Vila","orcid":"0000-0002-1086-4684","position":2,"is_corresponding":false},{"id":88713,"name":"Elisa De Franco","orcid":"0000-0002-1437-7891","position":3,"is_corresponding":false},{"id":430034,"name":"Matthew N. 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