Increased Soluble Interleukin 6 Receptors in Fabry Disease
Fabry disease (FD) is an X-linked lysosome storage disease that results in the accumulation of globotriaosylceramide (Gb3) throughout the body leading to irreversible target organ damage. As the role of secondary mediators (inflammatory molecules) and their mechanisms has not been fully elucidated,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/13/1/218 |
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| author | Livia Lenzini Elisabetta Iori Monica Vettore Giorgia Gugelmo Claudia Radu Andrea Padoan Gianni Carraro Paolo Simioni Lorenzo Calò Angelo Avogaro Gian Paolo Rossi Nicola Vitturi |
| author_facet | Livia Lenzini Elisabetta Iori Monica Vettore Giorgia Gugelmo Claudia Radu Andrea Padoan Gianni Carraro Paolo Simioni Lorenzo Calò Angelo Avogaro Gian Paolo Rossi Nicola Vitturi |
| author_sort | Livia Lenzini |
| collection | DOAJ |
| description | Fabry disease (FD) is an X-linked lysosome storage disease that results in the accumulation of globotriaosylceramide (Gb3) throughout the body leading to irreversible target organ damage. As the role of secondary mediators (inflammatory molecules) and their mechanisms has not been fully elucidated, we focused on the interleukin (IL)-6 system in adult FD patients and in matched healthy subjects. To obtain insights into the complex regulation of IL-6 actions, we used a novel approach that integrates information from plasma and exosomes of FD patients (n = 20) and of healthy controls (n = 15). Soluble IL-6 receptor (sIL-6R) levels were measured in plasma with the ELISA method, and membrane-bound IL-6R was quantified in plasma and urinary exosomes using flow cytometry. In FD patients, the levels of soluble IL-6R in plasma were higher than in control subjects (28.0 ± 5.4 ng/mL vs. 18.9 ± 5.4 ng/mL, <i>p</i> < 0.0001); they were also higher in FD subjects with the classical form as compared to those with the late-onset form of the disease (36.0 ± 11.4 ng/mL vs. 26.1 ± 4.5 ng/mL, <i>p</i> < 0.0001). The percentage of urinary exosomes positive for IL-6R was slightly lower in FD (97 ± 1 vs. 100 ± 0% of events positive for IL-6R, <i>p</i> < 0.05); plasma IL-6 levels were not increased. These results suggest a potential role of IL-6 in triggering the inflammatory response in FD. As in FD patients only the levels of sIL-6Rs are consistently higher than in healthy controls, the IL-6 pathogenic signal seems to prevail over the homeostatic one, suggesting a potential mechanism causing multi-systemic damage in FD. |
| first_indexed | 2024-03-08T15:03:15Z |
| format | Article |
| id | doaj.art-4e784599214e4d22bb1509edba329f96 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-08T15:03:15Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-4e784599214e4d22bb1509edba329f962024-01-10T15:01:38ZengMDPI AGJournal of Clinical Medicine2077-03832023-12-0113121810.3390/jcm13010218Increased Soluble Interleukin 6 Receptors in Fabry DiseaseLivia Lenzini0Elisabetta Iori1Monica Vettore2Giorgia Gugelmo3Claudia Radu4Andrea Padoan5Gianni Carraro6Paolo Simioni7Lorenzo Calò8Angelo Avogaro9Gian Paolo Rossi10Nicola Vitturi11Internal & Emergency Medicine Unit, Department of Medicine, Padova University Hospital, 35128 Padova, ItalyDivision of Metabolic Diseases, Department of Medicine, Padova University Hospital, 35128 Padova, ItalyDivision of Metabolic Diseases, Department of Medicine, Padova University Hospital, 35128 Padova, ItalyDivision of Clinical Nutrition, Department of Medicine, Padova University Hospital, 35128 Padova, ItalyGeneral Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, 35128 Padova, ItalyLaboratory Medicine Unit, Department of Medicine, Padova University Hospital, 35128 Padova, ItalyNephrology, Dialysis and Transplant Unit, Department of Medicine, Padova University Hospital, 35128 Padova, ItalyGeneral Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, 35128 Padova, ItalyNephrology, Dialysis and Transplant Unit, Department of Medicine, Padova University Hospital, 35128 Padova, ItalyDivision of Metabolic Diseases, Department of Medicine, Padova University Hospital, 35128 Padova, ItalyInternal & Emergency Medicine Unit, Department of Medicine, Padova University Hospital, 35128 Padova, ItalyDivision of Metabolic Diseases, Department of Medicine, Padova University Hospital, 35128 Padova, ItalyFabry disease (FD) is an X-linked lysosome storage disease that results in the accumulation of globotriaosylceramide (Gb3) throughout the body leading to irreversible target organ damage. As the role of secondary mediators (inflammatory molecules) and their mechanisms has not been fully elucidated, we focused on the interleukin (IL)-6 system in adult FD patients and in matched healthy subjects. To obtain insights into the complex regulation of IL-6 actions, we used a novel approach that integrates information from plasma and exosomes of FD patients (n = 20) and of healthy controls (n = 15). Soluble IL-6 receptor (sIL-6R) levels were measured in plasma with the ELISA method, and membrane-bound IL-6R was quantified in plasma and urinary exosomes using flow cytometry. In FD patients, the levels of soluble IL-6R in plasma were higher than in control subjects (28.0 ± 5.4 ng/mL vs. 18.9 ± 5.4 ng/mL, <i>p</i> < 0.0001); they were also higher in FD subjects with the classical form as compared to those with the late-onset form of the disease (36.0 ± 11.4 ng/mL vs. 26.1 ± 4.5 ng/mL, <i>p</i> < 0.0001). The percentage of urinary exosomes positive for IL-6R was slightly lower in FD (97 ± 1 vs. 100 ± 0% of events positive for IL-6R, <i>p</i> < 0.05); plasma IL-6 levels were not increased. These results suggest a potential role of IL-6 in triggering the inflammatory response in FD. As in FD patients only the levels of sIL-6Rs are consistently higher than in healthy controls, the IL-6 pathogenic signal seems to prevail over the homeostatic one, suggesting a potential mechanism causing multi-systemic damage in FD.https://www.mdpi.com/2077-0383/13/1/218Fabry diseaseinterleukin 6 receptorexosomesinflammation |
| spellingShingle | Livia Lenzini Elisabetta Iori Monica Vettore Giorgia Gugelmo Claudia Radu Andrea Padoan Gianni Carraro Paolo Simioni Lorenzo Calò Angelo Avogaro Gian Paolo Rossi Nicola Vitturi Increased Soluble Interleukin 6 Receptors in Fabry Disease Journal of Clinical Medicine Fabry disease interleukin 6 receptor exosomes inflammation |
| title | Increased Soluble Interleukin 6 Receptors in Fabry Disease |
| title_full | Increased Soluble Interleukin 6 Receptors in Fabry Disease |
| title_fullStr | Increased Soluble Interleukin 6 Receptors in Fabry Disease |
| title_full_unstemmed | Increased Soluble Interleukin 6 Receptors in Fabry Disease |
| title_short | Increased Soluble Interleukin 6 Receptors in Fabry Disease |
| title_sort | increased soluble interleukin 6 receptors in fabry disease |
| topic | Fabry disease interleukin 6 receptor exosomes inflammation |
| url | https://www.mdpi.com/2077-0383/13/1/218 |
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