d369c04130db7a2977167451250461ed pmc_10968350.pdf a26f77195eaccea5a5b01004f93e6c0c239b3d91 pmc_10968350.pdf de6a5056767a28871b846e709b1b6e2fc56d6543c1476c66856dccf9ef8368fb pmc_10968350.pdf Title: Serum Advanced Glycation End Products and Their Soluble Receptor as New Biomarkers in Systemic Lupus Erythematosus Subject: It has been postulated that advanced glycation end products (AGEs) and their soluble receptor (sRAGE) may play a relevant role as inducers in the chronic inflammatory pathway in various conditions, among them, in immune-mediated diseases such as systemic lupus erythematosus (SLE). However, previous studies show conflicting results about their association with SLE characteristics and their usefulness as disease biomarkers. We aimed to study the association of specific serum AGEs (pentosidine, N-(carboxymethyl)lysine (CML), N-(carboxyethyl)lysine (CEL)), sRAGE levels and AGEs (specific serum AGEs and skin AGEs) to sRAGE ratios with various disease parameters, in order to clarify their potential as new biomarkers in SLE and to study their relationship with cardiovascular disease (CVD). To this aim, serum pentosidine, CML, CEL and sRAGE were measured via ELISA, and skin AGEs levels were measured by skin autofluorescence. Correlations of pentosidine levels with demographic and clinical data, indexes of activity, accrual damage and patient-reported outcomes were analyzed through multiple linear regression models, while correlations of the rest of the AGEs, sRAGE and AGE to sRAGE ratios (non-normal) were analyzed using both an OLS regression model and a GML. All of the analyses were adjusted for confounders. A total of 119 SLE patients were recruited. Serum AGEs and sRAGEs were significantly associated with SLE activity indexes and/or demographic or disease characteristics: pentosidine with pulmonary manifestations; CML with anti-dsDNA antibodies, IL-6, disease duration and non-Caucasian ethnicities; CEL with anti-dsDNA antibodies, IL-6 and accumulated number of manifestations; and sRAGE with male gender, photosensitivity and being on specific immunosuppressants. These results suggest that the AGE–sRAGE axis may serve as a novel biomarker for managing and prognosticating this disease. Its correlation with certain antibodies, demographics and disease presentations may indicate a distinct clinical phenotype associated with varying levels of AGEs and/or sRAGE. The significance of specific AGE/sRAGE ratios, introduced in this study for the first time, warrants additional investigation in forthcoming research. Our study did not confirm the link between serum AGEs and CVD, which merits further exploration through studies designed for this specific purpose. Keywords: advanced glycation end products; systemic lupus erythematosus; cardiovascular disease; activity index Author: Irene Carrión-Barberà, Laura Triginer, Laura Tío, Carolina Pérez-García, Anna Ribes, Victoria Abad, Ana Pros, Jordi Monfort and Tarek Carlos Salman-Monte Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Mar 12 14:24:29 2024 CET ModDate: Tue Mar 12 14:28:16 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 25 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2215520 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ZSBPMM+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 SGPSDX+EURM10 Type 1 Builtin yes yes yes 16 0 MJSEEB+URWPalladioL-Bold Type 1 Custom yes yes yes 21 0 GOQKHK+URWPalladioL-Roma Type 1 Custom yes yes yes 27 0 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DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Subjects Destination: subsection.2.1 Item: Title: Variables Destination: subsection.2.2 Item: Title: Assessment of Specific Serum AGEs Destination: subsection.2.3 Item: Title: Statistical Methods Destination: subsection.2.4 Item: Title: Results Destination: section.3 Children: Item: Title: Pentosidine Destination: subsection.3.1 Children: Item: Title: Characteristics of SLE Patients According to Pentosidine Levels: Exploratory Analysis Destination: subsubsection.3.1.1 Item: Title: Correlations between Pentosidine and SLE Characteristics: Multivariate Analysis Destination: subsubsection.3.1.2 Item: Title: CML Destination: subsection.3.2 Children: Item: Title: Characteristics of SLE Patients According to CML Levels: Exploratory Analysis Destination: subsubsection.3.2.1 Item: Title: Correlations between CML and SLE Characteristics: Multivariate Analysis Destination: subsubsection.3.2.2 Item: Title: CEL Destination: subsection.3.3 Children: Item: Title: Characteristics of SLE Patients According to CEL Levels: Exploratory Analysis Destination: subsubsection.3.3.1 Item: Title: Correlations between CEL and SLE Characteristics: Multivariate Analysis Destination: subsubsection.3.3.2 Item: Title: Serum Receptor for Advanced Glycation End Products (sRAGE) Destination: subsection.3.4 Children: Item: Title: Characteristics of SLE Patients According to sRAGE Levels: Exploratory Analysis Destination: subsubsection.3.4.1 Item: Title: Correlations between sRAGE Levels and SLE Characteristics: Multivariate Analysis Destination: subsubsection.3.4.2 Item: Title: Ratios of Advanced Glycation End Products/Serum Soluble Receptor for Advanced Glycation End Products (AGEs/sRAGE) Destination: subsection.3.5 Children: Item: Title: Characteristics of SLE Patients According to Skin AGEs/sRAGE or Specific Serum AGEs/sRAGE Destination: subsubsection.3.5.1 Item: Title: Correlations between Skin AGEs/sRAGE or Specific Serum AGEs/sRAGE and SLE Characteristics: Multivariate Analysis Destination: subsubsection.3.5.2 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Serum Advanced Glycation End Products and Their Soluble Receptor as New Biomarkers in Systemic Lupus Erythematosus Author: Irene Carrión-Barberà, Laura Triginer, Laura Tío, Carolina Pérez-García, Anna Ribes, Victoria Abad, Ana Pros, Jordi Monfort and Tarek Carlos Salman-Monte Subject: It has been postulated that advanced glycation end products (AGEs) and their soluble receptor (sRAGE) may play a relevant role as inducers in the chronic inflammatory pathway in various conditions, among them, in immune-mediated diseases such as systemic lupus erythematosus (SLE). However, previous studies show conflicting results about their association with SLE characteristics and their usefulness as disease biomarkers. We aimed to study the association of specific serum AGEs (pentosidine, N-(carboxymethyl)lysine (CML), N-(carboxyethyl)lysine (CEL)), sRAGE levels and AGEs (specific serum AGEs and skin AGEs) to sRAGE ratios with various disease parameters, in order to clarify their potential as new biomarkers in SLE and to study their relationship with cardiovascular disease (CVD). To this aim, serum pentosidine, CML, CEL and sRAGE were measured via ELISA, and skin AGEs levels were measured by skin autofluorescence. Correlations of pentosidine levels with demographic and clinical data, indexes of activity, accrual damage and patient-reported outcomes were analyzed through multiple linear regression models, while correlations of the rest of the AGEs, sRAGE and AGE to sRAGE ratios (non-normal) were analyzed using both an OLS regression model and a GML. All of the analyses were adjusted for confounders. A total of 119 SLE patients were recruited. Serum AGEs and sRAGEs were significantly associated with SLE activity indexes and/or demographic or disease characteristics: pentosidine with pulmonary manifestations; CML with anti-dsDNA antibodies, IL-6, disease duration and non-Caucasian ethnicities; CEL with anti-dsDNA antibodies, IL-6 and accumulated number of manifestations; and sRAGE with male gender, photosensitivity and being on specific immunosuppressants. These results suggest that the AGE sRAGE axis may serve as a novel biomarker for managing and prognosticating this disease. Its correlation with certain antibodies, demographics and disease presentations may indicate a distinct clinical phenotype associated with varying levels of AGEs and/or sRAGE. The significance of specific AGE/sRAGE ratios, introduced in this study for the first time, warrants additional investigation in forthcoming research. Our study did not confirm the link between serum AGEs and CVD, which merits further exploration through studies designed for this specific purpose. 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