{"doi":"10.1101/2023.08.29.23294775","title":"Novel autoantibodies help diagnose anti-SSA antibody negative Sjögren’s disease and predict abnormal labial salivary gland pathology","abstract":"Objectives: Sj□gren's disease (SjD) diagnosis requires either positive anti-SSA antibodies or a labial salivary gland biopsy with a positive focus score (FS). One-third of SjD patients lack anti-SSA antibodies (SSA-), requiring a positive FS for diagnosis. Our objective was to identify novel autoantibodies to diagnose 'seronegative' SjD. Methods: IgG binding to a high density whole human peptidome array was quantified using sera from SSA- SjD cases and matched non-autoimmune controls. We identified the highest bound peptides using empirical Bayesian statistical filters, which we confirmed in an independent cohort comprising SSA- SjD (n=76), sicca controls without autoimmunity (n=75), and autoimmune controls (SjD features but not meeting SjD criteria; n=41). In this external validation, we used non-parametric methods for peptide abundance and controlled false discovery rate in group comparisons. For predictive modeling, we used logistic regression, model selection methods, and cross-validation to identify clinical and peptide variables that predict SSA- SjD and FS positivity. Results: IgG against a peptide from D-aminoacyl-tRNA deacylase (DTD2) was bound more in SSA- SjD than sicca controls (p=.004) and more than combined controls (sicca and autoimmune controls combined; p=0.003). IgG against peptides from retroelement silencing factor-1 (RESF1) and DTD2, were bound more in FS-positive than FS-negative participants (p=.010; p=0.012). A predictive model incorporating clinical variables showed good discrimination between SjD versus control (AUC 74%) and between FS-positive versus FS-negative (AUC 72%). Conclusion: We present novel autoantibodies in SSA- SjD that have good predictive value for SSA- SjD and FS-positivity. KEY MESSAGES: What is already known on this topic - Seronegative (anti-SSA antibody negative [SSA-]) Sjögren's disease (SjD) requires a labial salivary gland biopsy for diagnosis, which is challenging to obtain and interpret. What this study adds - We identified novel autoantibodies in SSA- SjD that, when combined with readily available clinical variables, provide good predictive ability to discriminate 1) SSA- SjD from control participants and 2) abnormal salivary gland biopsies from normal salivary gland biopsies. How this study might affect research, practice or policy - This study provides novel diagnostic antibodies addressing the critical need for improvement of SSA- SjD diagnostic tools.","journal":"medRxiv","year":2023,"id":400586,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9703,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1094340,"name":"Zihao Zheng","orcid":"0000-0002-9381-5705","position":1,"is_corresponding":false},{"id":404141,"name":"Michael Lasarev","orcid":"0000-0002-1896-2705","position":2,"is_corresponding":false},{"id":510762,"name":"Roxana Alexandridis","orcid":null,"position":3,"is_corresponding":false},{"id":399506,"name":"Michael A. Newton","orcid":"0000-0001-9038-878X","position":4,"is_corresponding":false},{"id":342390,"name":"Miriam A. Shelef","orcid":"0000-0002-8842-0303","position":5,"is_corresponding":false},{"id":468973,"name":"Sara S. McCoy","orcid":"0000-0002-5293-4185","position":6,"is_corresponding":false},{"id":912720,"name":"Maxwell Parker","orcid":null,"position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T01:20:04.010538Z","pmid":"37693588","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":[]}