Cordero Santamaría, Óscar JavierViéitez González, IreneAltabás González, IreneNuño Nuño, LauraVillalba Yllán, AlejandroNovella Navarro , MartaPeiteado López, DianaMiranda-Carús, María-EugeniaBalsa Criado, AlejandroVarela Calviño, RubénGómez Touriño, Iria MaríaPego Reigosa, José María2022-08-292022-08-292022Archivum Immunologiae et Therapiae Experimentalis 70, 12 (2022). https://doi.org/10.1007/s00005-022-00649-60004-069Xhttp://hdl.handle.net/10347/29165In rheumatoid arthritis (RA), the identifcation of biomarkers to adjust treatment intensity and to correctly diagnose the disease in early stages still constitutes a challenge and, as such, novel biomarkers are needed. We proposed that autoantibodies (aAbs) against CD26 (DPP4) might have both etiological importance and clinical value. Here, we perform a prospective study of the potential diagnostic power of Anti-CD26 aAbs through their quantifcation in plasmas from 106 treatment-naïve early and undiferentiated AR. Clinical antibodies, Anti-CD26 aAbs, and other disease-related biomarkers were measured in plasmas obtained in the frst visit from patients, which were later classifed as RA and non-RA according to the American College of Rheumatology criteria. Two diferent isotype signatures were found among ten groups of patients, one for AntiCD26 IgA and other for Anti-CD26 IgG and IgM isotypes, both converging in patients with arthritis (RA and Unresolved Undiferentiated Arthritis: UUA), who present elevated levels of all three isotypes. The four UUA patients, unresolved after two years, were ACPA and rheumatic factor (RF) negatives. In the whole cohort, 51.3% of ACPA/RF seronegatives were Anti-CD26 positives, and a similar frequency was observed in the seropositive RA patients. Only weak associations of the three isotypes with ESR, CRP and disease activity parameters were observed. Anti-CD26 aAbs are present in treatmentnaïve early arthritis patients, including ACPA and RF seronegative individuals, suggestive of a potential pathogenic and/or biomarker role of Anti-CD26 aAbs in the development of rheumatic diseaseseng© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/AutoantibodiesCD26Anti-CD26Early rheumatoid arthritisAutoimmunityEtiologyjournal article10.1007/s00005-022-00649-61661-4917open access