{"doi":"10.2337/db23-0568","title":"Cell-Surface ZnT8 Antibody Prevents and Reverses Autoimmune Diabetes in Mice","abstract":"Type 1 diabetes (T1D) is an autoimmune disease in which pathogenic lymphocytes target autoantigens expressed in pancreatic islets, leading to the destruction of insulin-producing β-cells. Zinc transporter 8 (ZnT8) is a major autoantigen abundantly present on the β-cell surface. This unique molecular target offers the potential to shield β-cells against autoimmune attacks in T1D. Our previous work showed that a monoclonal antibody (mAb43) against cell-surface ZnT8 could home in on pancreatic islets and prevent autoantibodies from recognizing β-cells. This study demonstrates that mAb43 binds to exocytotic sites on the β-cell surface, masking the antigenic exposure of ZnT8 and insulin after glucose-stimulated insulin secretion. In vivo administration of mAb43 to NOD mice selectively increased the proportion of regulatory T cells in the islet, resulting in complete and sustained protection against T1D onset as well as reversal of new-onset diabetes. The mAb43-induced self-tolerance was reversible after treatment cessation, and no adverse effects were exhibited during long-term monitoring. Our findings suggest that mAb43 masking of the antigenic exposure of β-cells suppresses the immunological cascade from B-cell antigen presentation to T cell-mediated β-cell destruction, providing a novel islet-targeted and antigen-specific immunotherapy to prevent and reverse clinical T1D.","journal":"Diabetes","year":2024,"id":441948,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9683,"is_data_producer":false,"deposit_databanks":null,"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":1254974,"name":"Zheng Guo","orcid":"0000-0003-2105-4537","position":1,"is_corresponding":false},{"id":299042,"name":"Dylan C. Sarver","orcid":"0000-0002-4578-8757","position":2,"is_corresponding":false},{"id":571561,"name":"G. William Wong","orcid":"0000-0002-5286-6506","position":3,"is_corresponding":false},{"id":1255474,"name":"Shumei Yun","orcid":null,"position":4,"is_corresponding":false},{"id":463868,"name":"Aaron W. Michels","orcid":"0000-0003-3766-5244","position":5,"is_corresponding":false},{"id":39947,"name":"Liping Yu","orcid":"0000-0003-0664-2154","position":6,"is_corresponding":false},{"id":1073966,"name":"Chandan Sona","orcid":"0000-0003-3107-016X","position":7,"is_corresponding":false},{"id":1073972,"name":"Matthew N. Poy","orcid":"0000-0002-4904-2426","position":8,"is_corresponding":false},{"id":304327,"name":"Maria L. Golson","orcid":"0000-0002-2927-2013","position":9,"is_corresponding":false},{"id":716638,"name":"Dax Fu","orcid":"0000-0002-2663-1316","position":10,"is_corresponding":false},{"id":930058,"name":"Devi Kasinathan","orcid":"0000-0001-7653-0380","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:01:11.152920Z","pmid":"38387059","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}