{"doi":"10.1002/acr2.11309","title":"Combinations of Anticyclic Citrullinated Protein Antibody, Rheumatoid Factor, and Serum Calprotectin Positivity Are Associated With the Diagnosis of Rheumatoid Arthritis Within 3 Years","abstract":"OBJECTIVE: To evaluate the prevalence of elevations of anti-cyclic citrullinated peptide-3 (anti-CCP3) antibody, rheumatoid factor IgM (RF-IgM) and serum calprotectin (sCP) in pre-rheumatoid arthritis (RA) as well as the diagnostic accuracies of these biomarkers for the timing of diagnosis of future RA. METHODS: A total of 215 RA cases, each with approximately three pre-RA diagnoses and one post-RA diagnosis serum sample, and controls were identified from the Department of Defense Serum Repository. All case samples and a single sample from each control subject were tested for anti-CCP3 (IgG), RF-IgM, and sCP. The diagnostic accuracies of biomarkers for future RA were evaluated. RESULTS: Anti-CCP3, RF-IgM, and sCP were elevated in pre-RA, with anti-CCP3 and sCP significantly elevated compared with RF-IgM at the earliest time points. Within the cases, the combination of anti-CCP3 and RF-IgM positivity had a positive predictive value (PPV) of 35.6% for a diagnosis of RA in 3 years or less, which is significantly higher than the PPV of 18.7% for anti-CCP3 positivity alone (P < 0.001). A combination of anti-CCP3, RF-IgM, and sCP had the highest PPV (53.0%) for a diagnosis of RA in 3 years or less; however, this was not significantly higher than the PPV for anti-CCP3 and RF-IgM positivity (P = 0.248). CONCLUSION: Anti-CCP3, RF-IgM, and sCP are elevated in pre-RA; furthermore, combinations of elevations of these biomarkers are more commonly seen in the period of less than or equal to 3 years to diagnosis. This may be considered in creating inclusion criteria in prevention trials in RA. In addition, the biologic relationships of these biomarkers in pre-RA need exploration.","journal":"ACR Open Rheumatology","year":2021,"id":178607,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8719,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":646880,"name":"Ryan Peterson","orcid":"0000-0002-4650-5798","position":1,"is_corresponding":false},{"id":725160,"name":"Dylan T. Bergstedt","orcid":null,"position":2,"is_corresponding":false},{"id":335240,"name":"Lindsay B. Kelmenson","orcid":"0000-0002-7809-6722","position":3,"is_corresponding":false},{"id":342496,"name":"M. Kristen Demoruelle","orcid":"0000-0002-2563-5155","position":4,"is_corresponding":false},{"id":314417,"name":"Ted R. Mikuls","orcid":"0000-0002-0897-2272","position":5,"is_corresponding":false},{"id":335241,"name":"Jess D. Edison","orcid":"0000-0002-5260-0273","position":6,"is_corresponding":false},{"id":725161,"name":"Mark C. Parish","orcid":null,"position":7,"is_corresponding":false},{"id":335239,"name":"Marie L. Feser","orcid":"0009-0003-0598-853X","position":8,"is_corresponding":false},{"id":661533,"name":"Ashley Frazer‐Abel","orcid":"0000-0002-7415-8543","position":9,"is_corresponding":false},{"id":725162,"name":"Laura K. Moss","orcid":null,"position":10,"is_corresponding":false},{"id":251393,"name":"Michael Mähler","orcid":"0000-0002-7919-0948","position":11,"is_corresponding":false},{"id":41942,"name":"V. Michael Holers","orcid":"0000-0002-5634-7746","position":12,"is_corresponding":false},{"id":305659,"name":"Kevin D. Deane","orcid":"0000-0003-2211-4861","position":13,"is_corresponding":false},{"id":725159,"name":"Leah F. Bettner","orcid":null,"position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-18T23:47:40.592580Z","pmid":"34288565","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":[]}