Insight into the Interplay of Gd-IgA1, HMGB1, RAGE and PCDH1 in IgA Vasculitis (IgAV)

Scientific paper - Original scientific paper

• Author: Martina Held
• Author: Ana Kozmar
• Author: Mario Šestan
• Author: Daniel Turudić
• Author: Nastasia Kifer
• Author: Saša Sršen
• Author: Alenka Gagro
• Author: Marijan Frković
• Author: Marija Jelušić
• Author's institution: University of Zagreb; School of Medicine; (Department of Pediatrics)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pediatrics

Abstract (english)

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... More 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 < 0.001). Concentrations of HMGB1 (5573 pg/mL vs. 3477 pg/mL vs. 1088 pg/mL, p < 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 (146.7–542.7) ng/mmol vs. 133.2 (85.9–318.6) ng/mmol, p = 0.049) and significantly positively correlated with the urine albumine to creatinine ratio (τ = 0.184, p < 0.05), the number of erythrocytes in urine samples (τ = 0.193, p < 0.05) and with the outcome of nephritis (τ = 0.287, p < 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. Less

• Keywords (english): Biomarkers / blood; Biomarkers / urine; Cadherins / blood; Cadherins / genetics; Cadherins / urine; Case-Control Studies; Child; Child, Preschool; Female; HMGB1 Protein / blood; HMGB1 Protein / urine; Humans; IgA Vasculitis / blood; IgA Vasculitis / urine; Immunoglobulin A / blood; Male; Prospective Studies; Protocadherins; Receptor for Advanced Glycation End Products / blood
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: International Journal of Molecular Sciences
• Numbering: vol. 25, no. 8, 4383
• e-ISSN: 1422-0067
• DOI: https://doi.org/10.3390/ijms25084383
• URN:NBN: urn:nbn:hr:105:217666
• Publication: 2024-04-16
• Document URL: https://www.mdpi.com/1422-0067/25/8/4383
• Type of resource: Text
• Access conditions: Open access
• Created on: 2025-03-03 08:54:02