{"doi":"10.2337/db22-0477","title":"Cell-Surface Autoantibody Targets Zinc Transporter-8 (ZnT8) for In Vivo β-Cell Imaging and Islet-Specific Therapies","abstract":"Type 1 diabetes (T1D) is a disease in which autoimmune attacks are directed at the insulin-producing β-cell in the pancreatic islet. Autoantigens on the β-cell surface membrane are specific markers for molecular recognition and targets for engagement by autoreactive B lymphocytes, which produce islet cell surface autoantibody (ICSA) upon activation. We report the cloning of an ICSA (mAb43) that recognizes a major T1D autoantigen, ZnT8, with a subnanomolar binding affinity and conformation specificity. We demonstrate that cell-surface binding of mAb43 protects the extracellular epitope of ZnT8 against immunolabeling by serum ICSA from a patient with T1D. Furthermore, mAb43 exhibits in vitro and ex vivo specificity for islet cells, mirroring the exquisite specificity of islet autoimmunity in T1D. Systemic administration of mAb43 yields a pancreas-specific biodistribution in mice and islet homing of an mAb43-linked imaging payload through the pancreatic vasculature, thereby validating the in vivo specificity of mAb43. Identifying ZnT8 as a major antigenic target of ICSA allows for research into the molecular recognition and engagement of autoreactive B cells in the chronic phase of T1D progression. The in vivo islet specificity of mAb43 could be further exploited to develop in vivo imaging and islet-specific immunotherapies.","journal":"Diabetes","year":2022,"id":268386,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.964,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":930058,"name":"Devi Kasinathan","orcid":"0000-0001-7653-0380","position":1,"is_corresponding":false},{"id":717357,"name":"Chengfeng Merriman","orcid":null,"position":2,"is_corresponding":false},{"id":369808,"name":"Maki Nakayama","orcid":"0000-0002-0009-3687","position":3,"is_corresponding":false},{"id":322713,"name":"Hua Li","orcid":"0000-0003-1903-836X","position":4,"is_corresponding":false},{"id":315159,"name":"Huilin Li","orcid":"0000-0002-8288-7068","position":5,"is_corresponding":false},{"id":281747,"name":"Cheng‐Jian Xu","orcid":"0000-0003-1586-4672","position":6,"is_corresponding":false},{"id":571561,"name":"G. William Wong","orcid":"0000-0002-5286-6506","position":7,"is_corresponding":false},{"id":39947,"name":"Liping Yu","orcid":"0000-0003-0664-2154","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":930057,"name":"Zheng Guo","orcid":"0009-0005-0330-7221","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T00:27:10.233250Z","pmid":"36448936","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":[]}