{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:36:40Z","timestamp":1787636200690,"version":"build-2736575974"},"reference-count":29,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Advanced glycation end products (AGEs) accumulate under chronic inflammation and metabolic stress and may contribute to long-term tissue damage. Skin autofluorescence (SAF) enables non-invasive assessment of tissue AGE accumulation, but data in inflammatory rheumatic diseases remain limited. The present study evaluated AGE-SAF levels in patients with seropositive rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and investigated their associations with disease activity, inflammatory markers, metabolic parameters, and comorbidities. Patients with RA and AS, along with healthy controls, were included. AGE-SAF was measured non-invasively. Disease activity was assessed using the Disease Activity Score in 28 joints (DAS28) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Between-group comparisons were performed both crudely and after multivariable adjustment for age, sex, and body mass index (BMI). Logistic regression and receiver operating characteristic (ROC) analyses were used to describe the exploratory discriminative performance of AGE-SAF, and propensity score analyses were conducted as sensitivity analyses to address baseline imbalance. In crude comparisons, AGE-SAF levels were higher in RA than in AS and controls, and higher in AS than in controls (p &lt; 0.001). After adjustment for age, sex, and BMI, AGE-SAF remained significantly elevated in both RA (\u03b2 = 0.440, 95% CI 0.298\u20130.583, p &lt; 0.001) and AS (\u03b2 = 0.304, 95% CI 0.183\u20130.425, p &lt; 0.001) compared with controls; however, the difference between RA and AS was no longer statistically significant (\u03b2 = 0.136, 95% CI \u22120.051 to 0.323, p = 0.154). Exploratory ROC analyses showed good discrimination for RA versus controls (AUC = 0.851) and moderate discrimination for AS versus controls (AUC = 0.695), whereas discrimination between RA and AS was limited (AUC = 0.670). In overlap-weighted sensitivity analysis, the RA-AS difference remained non-significant (\u03b2 = 0.161, p = 0.293). AGE-SAF is elevated in inflammatory rheumatic diseases compared with healthy controls, and this elevation persists after adjustment for age, sex, and BMI. Although crude AGE-SAF values were higher in RA than in AS, this difference attenuated after confounder adjustment, indicating that a substantial part of the between-disease difference is attributable to demographic and treatment-related imbalance. AGE-SAF may therefore reflect cumulative disease-related and vascular\u2013metabolic burden across both diseases rather than a disease-specific phenomenon.<\/jats:p>","DOI":"10.3390\/ijms27094027","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:20:25Z","timestamp":1777551625000},"page":"4027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tissue Advanced Glycation End Product Accumulation and Its Association with Clinical and Laboratory Features, Inflammatory Indices, and Comorbidities in Rheumatoid Arthritis and Ankylosing Spondylitis: A Case\u2013Control Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7220-0288","authenticated-orcid":false,"given":"Altu\u011f","family":"G\u00fcner","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Bursa City Hospital, 16110 Bursa, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6010-7315","authenticated-orcid":false,"given":"Taner","family":"Dandino\u011flu","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Bursa City Hospital, 16110 Bursa, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1001\/jama.2018.13103","article-title":"Diagnosis and management of rheumatoid arthritis: A review","volume":"320","author":"Aletaha","year":"2018","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0140-6736(16)31591-4","article-title":"Axial spondyloarthritis","volume":"390","author":"Sieper","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s001250051591","article-title":"Advanced glycation end-products: A review","volume":"44","author":"Singh","year":"2001","journal-title":"Diabetologia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.tcm.2005.08.003","article-title":"The RAGE axis and endothelial dysfunction: Maladaptive roles in the diabetic vasculature and beyond","volume":"15","author":"Ramasamy","year":"2005","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"107282","DOI":"10.1016\/j.phrs.2024.107282","article-title":"Activation and modulation of the AGEs\u2013RAGE axis: Implications for inflammatory pathologies and therapeutic interventions\u2014A review","volume":"206","author":"Zhou","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.cardiores.2004.05.001","article-title":"Advanced glycation end products and vascular inflammation: Implications for accelerated atherosclerosis in diabetes","volume":"63","author":"Basta","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s10020-024-00905-9","article-title":"Advanced glycation end products and reactive oxygen species: Uncovering the potential role of ferroptosis in diabetic complications","volume":"30","author":"Chen","year":"2024","journal-title":"Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1161\/CIRCULATIONAHA.106.621854","article-title":"Advanced glycation end products: Sparking the development of diabetic vascular injury","volume":"114","author":"Goldin","year":"2006","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.redox.2013.12.016","article-title":"Role of advanced glycation end products in cellular signaling","volume":"2","author":"Ott","year":"2014","journal-title":"Redox Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bondy, S., and Maiese, K. (2010). Advanced glycation end products, RAGE, and aging. Aging and Age-Related Disorders, Springer.","DOI":"10.1007\/978-1-60761-602-3"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1935","DOI":"10.1002\/wnan.1935","article-title":"Receptor for advanced glycation end-products: Biological significance and imaging applications","volume":"16","author":"Dobrucki","year":"2024","journal-title":"WIREs Nanomed. Nanobiotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"R205","DOI":"10.1186\/ar3538","article-title":"Advanced glycation endproducts are increased in rheumatoid arthritis patients with controlled disease","volume":"13","author":"Hinkema","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, Z., Tu, C., Chen, X., and He, R. (2025). Advanced glycation end products in disease development and potential interventions. Antioxidants, 14.","DOI":"10.3390\/antiox14040492"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1007\/s00125-004-1451-2","article-title":"Simple non-invasive assessment of advanced glycation endproduct accumulation","volume":"47","author":"Meerwaldt","year":"2004","journal-title":"Diabetologia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1097\/MNH.0b013e32833e9259","article-title":"Skin autofluorescence as a measure of advanced glycation endproduct deposition: A novel risk marker in chronic kidney disease","volume":"19","author":"Smit","year":"2010","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6212","DOI":"10.1158\/1078-0432.CCR-14-0442","article-title":"Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma","volume":"20","author":"Hu","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"41370","DOI":"10.18632\/oncotarget.5629","article-title":"Prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet in patients with gastric carcinoma: A retrospective cohort study","volume":"6","author":"Chen","year":"2015","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.hpb.2021.06.414","article-title":"Superiority of CRP\u2013albumin\u2013lymphocyte index (CALLY index) as a non-invasive prognostic biomarker after hepatectomy for hepatocellular carcinoma","volume":"24","author":"Iida","year":"2022","journal-title":"HPB"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.molmet.2013.11.006","article-title":"Vascular effects of advanced glycation endproducts: Clinical effects and molecular mechanisms","volume":"3","author":"Stirban","year":"2014","journal-title":"Mol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1136\/ard.2009.126532","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs","volume":"69","author":"Smolen","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1136\/ard-2022-223296","article-title":"ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update","volume":"82","author":"Ramiro","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_22","first-page":"62","article-title":"Steroid diabetes: From mechanism to treatment?","volume":"72","author":"Diamant","year":"2014","journal-title":"Neth. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1681\/ASN.2005020144","article-title":"Skin autofluorescence, a measure of cumulative metabolic stress and advanced glycation end products, predicts mortality in hemodialysis patients","volume":"16","author":"Meerwaldt","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4161\/oxim.3.2.11148","article-title":"Advanced glycation end products, oxidative stress and diabetic nephropathy","volume":"3","author":"Yamagishi","year":"2010","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1136\/ard.2009.108233","article-title":"The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis, (part II): Validation and final selection","volume":"68","author":"Rudwaleit","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/art.1780380107","article-title":"Modified disease activity scores that include twenty-eight-joint counts: Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis","volume":"38","author":"Prevoo","year":"1995","journal-title":"Arthritis Rheum."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1136\/ard.2007.084459","article-title":"Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate","volume":"68","author":"Wells","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_28","first-page":"2286","article-title":"A new approach to defining disease status in ankylosing spondylitis: The Bath Ankylosing Spondylitis Disease Activity Index","volume":"21","author":"Garrett","year":"1994","journal-title":"J. Rheumatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s00296-003-0432-y","article-title":"A Turkish version of the Bath Ankylosing Spondylitis Disease Activity Index: Reliability and validity","volume":"25","author":"Akkoc","year":"2005","journal-title":"Rheumatol. Int."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/4027\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T04:19:51Z","timestamp":1778386791000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/4027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":29,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27094027"],"URL":"https:\/\/doi.org\/10.3390\/ijms27094027","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]}}}