Systemic immune profile in Prader-Willi syndrome: elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factor
Abstract Background Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental syndrome with highly increased risk of obesity and cardiovascular disease (CVD). Recent evidence suggests that inflammation is implicated in the pathogenesis. Here we investigated CVD related immune markers to shed...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-023-02730-5 |
| _version_ | 1797778714761625600 |
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| author | Sigrun Hope Terje Nærland Svein Olav Kolset Thor Ueland Ole A. Andreassen Marianne Nordstrøm |
| author_facet | Sigrun Hope Terje Nærland Svein Olav Kolset Thor Ueland Ole A. Andreassen Marianne Nordstrøm |
| author_sort | Sigrun Hope |
| collection | DOAJ |
| description | Abstract Background Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental syndrome with highly increased risk of obesity and cardiovascular disease (CVD). Recent evidence suggests that inflammation is implicated in the pathogenesis. Here we investigated CVD related immune markers to shed light on pathogenetic mechanisms. Methods We performed a cross-sectional study with 22 participants with PWS and 22 healthy controls (HC), and compared levels of 21 inflammatory markers that reflect activity in different aspects of CVD related immune pathways and analyzed their association with clinical CVD risk factors. Results Serum levels of matrix metalloproteinase 9 (MMP-9) was (median (range)) 121 (182) ng/ml in PWS versus 44 (51) ng/ml in HC, p = 1 × 10-9), myeloperoxidase (MPO) was 183 (696) ng/ml versus 65 (180) ng/ml, p = 1 × 10-5) and macrophage inhibitory factor (MIF) was 46 (150) ng/ml versus 121 (163) ng/ml (p = 1 × 10-3), after adjusting for age and sex. Also other markers tended to be elevated (OPG, sIL2RA, CHI3L1, VEGF) but not significantly after Bonferroni correction (p > 0.002). As expected PWS had higher body mass index, waist circumference, leptin, C-reactive protein, glycosylated hemoglobin (HbA1c), VAI and cholesterol, but MMP-9, MPO and MIF remained significantly different in PWS after adjustment for these clinical CVD risk factors. Conclusion PWS had elevated levels of MMP-9 and MPO and of reduced levels of MIF, which were not secondary to comorbid CVD risk factors. This immune profile suggests enhanced monocyte/neutrophil activation, impaired macrophage inhibition with enhanced extracellular matrix remodeling. These findings warrant further studies targeting these immune pathways in PWS. |
| first_indexed | 2024-03-12T23:21:31Z |
| format | Article |
| id | doaj.art-9abfdc7d34f94385b33ee349a647763f |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-03-12T23:21:31Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-9abfdc7d34f94385b33ee349a647763f2023-07-16T11:27:39ZengBMCOrphanet Journal of Rare Diseases1750-11722023-07-011811910.1186/s13023-023-02730-5Systemic immune profile in Prader-Willi syndrome: elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factorSigrun Hope0Terje Nærland1Svein Olav Kolset2Thor Ueland3Ole A. Andreassen4Marianne Nordstrøm5K.G. Jebsen Centre for Neurodevelopmental disorders, Institute of Clinical Medicine, University of OsloK.G. Jebsen Centre for Neurodevelopmental disorders, Institute of Clinical Medicine, University of OsloDepartment of Nutrition, Institute of Basic Medical Sciences, University of OsloResearch Institute of Internal Medicine, Oslo University HospitalK.G. Jebsen Centre for Neurodevelopmental disorders, Institute of Clinical Medicine, University of OsloDepartment of Nutrition, Institute of Basic Medical Sciences, University of OsloAbstract Background Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental syndrome with highly increased risk of obesity and cardiovascular disease (CVD). Recent evidence suggests that inflammation is implicated in the pathogenesis. Here we investigated CVD related immune markers to shed light on pathogenetic mechanisms. Methods We performed a cross-sectional study with 22 participants with PWS and 22 healthy controls (HC), and compared levels of 21 inflammatory markers that reflect activity in different aspects of CVD related immune pathways and analyzed their association with clinical CVD risk factors. Results Serum levels of matrix metalloproteinase 9 (MMP-9) was (median (range)) 121 (182) ng/ml in PWS versus 44 (51) ng/ml in HC, p = 1 × 10-9), myeloperoxidase (MPO) was 183 (696) ng/ml versus 65 (180) ng/ml, p = 1 × 10-5) and macrophage inhibitory factor (MIF) was 46 (150) ng/ml versus 121 (163) ng/ml (p = 1 × 10-3), after adjusting for age and sex. Also other markers tended to be elevated (OPG, sIL2RA, CHI3L1, VEGF) but not significantly after Bonferroni correction (p > 0.002). As expected PWS had higher body mass index, waist circumference, leptin, C-reactive protein, glycosylated hemoglobin (HbA1c), VAI and cholesterol, but MMP-9, MPO and MIF remained significantly different in PWS after adjustment for these clinical CVD risk factors. Conclusion PWS had elevated levels of MMP-9 and MPO and of reduced levels of MIF, which were not secondary to comorbid CVD risk factors. This immune profile suggests enhanced monocyte/neutrophil activation, impaired macrophage inhibition with enhanced extracellular matrix remodeling. These findings warrant further studies targeting these immune pathways in PWS.https://doi.org/10.1186/s13023-023-02730-5Prader-Willi Syndrome15q11-q13ObesityInflammationCardiovascularExtracellular matrix |
| spellingShingle | Sigrun Hope Terje Nærland Svein Olav Kolset Thor Ueland Ole A. Andreassen Marianne Nordstrøm Systemic immune profile in Prader-Willi syndrome: elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factor Orphanet Journal of Rare Diseases Prader-Willi Syndrome 15q11-q13 Obesity Inflammation Cardiovascular Extracellular matrix |
| title | Systemic immune profile in Prader-Willi syndrome: elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factor |
| title_full | Systemic immune profile in Prader-Willi syndrome: elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factor |
| title_fullStr | Systemic immune profile in Prader-Willi syndrome: elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factor |
| title_full_unstemmed | Systemic immune profile in Prader-Willi syndrome: elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factor |
| title_short | Systemic immune profile in Prader-Willi syndrome: elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factor |
| title_sort | systemic immune profile in prader willi syndrome elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factor |
| topic | Prader-Willi Syndrome 15q11-q13 Obesity Inflammation Cardiovascular Extracellular matrix |
| url | https://doi.org/10.1186/s13023-023-02730-5 |
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