{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T18:03:44Z","timestamp":1777485824925,"version":"3.51.4"},"reference-count":71,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Croatian Science Foundation","award":["IP-2019-04-8822"],"award-info":[{"award-number":["IP-2019-04-8822"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The pathogenesis of IgAV, the most common systemic vasculitis in childhood, appears to be complex and requires further elucidation. We aimed to investigate the potential role of galactose-deficient immunoglobulin A1 (Gd-IgA1), high-mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE) and protocadherin 1 (PCDH1) in the pathogenesis of IgAV. Our prospective study enrolled 86 patients with IgAV and 70 controls. HMGB1, RAGE, Gd-IgA1 and PCDH1 in serum and urine were determined by the enzyme-linked immunosorbent assay (ELISA) method at the onset of the disease and after a six-month interval in patients and once in the control group. Serum concentrations of HMGB1, RAGE and PCDH1 and urinary concentrations of HMGB1, RAGE, Gd-IgA1 and PCDH1 were significantly higher in patients with IgAV than in the control group (p &lt; 0.001). Concentrations of HMGB1 (5573 pg\/mL vs. 3477 pg\/mL vs. 1088 pg\/mL, p &lt; 0.001) and RAGE (309 pg\/mL vs. 302.4 pg\/mL vs. 201.3 pg\/mL, p = 0.012) in the serum of patients remained significantly elevated when the disease onset was compared with the six-month follow-up interval, and thus could be a potential marker of disease activity. Urinary concentration of HMGB1 measured in the follow-up period was higher in patients with nephritis compared to IgAV without nephritis (270.9 (146.7\u2013542.7) ng\/mmol vs. 133.2 (85.9\u2013318.6) ng\/mmol, p = 0.049) and significantly positively correlated with the urine albumine to creatinine ratio (\u03c4 = 0.184, p &lt; 0.05), the number of erythrocytes in urine samples (\u03c4 = 0.193, p &lt; 0.05) and with the outcome of nephritis (\u03c4 = 0.287, p &lt; 0.05); therefore, HMGB1 could be a potential tool for monitoring patients with IgAV who develop nephritis. Taken together, our results imply a possible interplay of Gd-IgA1, HMGB1, RAGE and PCDH1 in the development of IgAV. The identification of sensitive biomarkers in IgAV may provide disease prevention and future therapeutics.<\/jats:p>","DOI":"10.3390\/ijms25084383","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T08:41:06Z","timestamp":1713256866000},"page":"4383","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Insight into the Interplay of Gd-IgA1, HMGB1, RAGE and PCDH1 in IgA Vasculitis (IgAV)"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4925-8948","authenticated-orcid":false,"given":"Martina","family":"Held","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Kozmar","sequence":"additional","affiliation":[{"name":"Department of Laboratory Diagnostics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1092-6491","authenticated-orcid":false,"given":"Mario","family":"Sestan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6598-7489","authenticated-orcid":false,"given":"Daniel","family":"Turudic","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nastasia","family":"Kifer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6555-2613","authenticated-orcid":false,"given":"Sasa","family":"Srsen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Split School of Medicine, University Hospital Centre Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6308-6460","authenticated-orcid":false,"given":"Alenka","family":"Gagro","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Zagreb, Medical Faculty Osijek, Josip Juraj Strossmayer University of Osijek, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1520-3375","authenticated-orcid":false,"given":"Marijan","family":"Frkovic","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Jelusic","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"853724","DOI":"10.3389\/fped.2022.853724","article-title":"New insights and challenges associated with IgA vasculitis and IgA vasculitis with nephritis\u2014Is it time to change the paradigm of the most common systemic vasculitis in childhood?","volume":"10","author":"Jelusic","year":"2022","journal-title":"Front. 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