Age and Sex-Associated Changes of Complement Activity and Complement Levels in a Healthy Caucasian Population
Introduction: The complement system is essential for an adequate immune response. Much attention has been given to the role of complement in disease. However, to better understand complement in pathology, it is crucial to first analyze this system under different physiological conditions. The aim of...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-11-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02664/full |
| _version_ | 1828336228724899840 |
|---|---|
| author | Mariana Gaya da Costa Felix Poppelaars Felix Poppelaars Cees van Kooten Tom E. Mollnes Tom E. Mollnes Tom E. Mollnes Francesco Tedesco Reinhard Würzner Leendert A. Trouw Leendert A. Trouw Lennart Truedsson Mohamed R. Daha Mohamed R. Daha Anja Roos Marc A. Seelen |
| author_facet | Mariana Gaya da Costa Felix Poppelaars Felix Poppelaars Cees van Kooten Tom E. Mollnes Tom E. Mollnes Tom E. Mollnes Francesco Tedesco Reinhard Würzner Leendert A. Trouw Leendert A. Trouw Lennart Truedsson Mohamed R. Daha Mohamed R. Daha Anja Roos Marc A. Seelen |
| author_sort | Mariana Gaya da Costa |
| collection | DOAJ |
| description | Introduction: The complement system is essential for an adequate immune response. Much attention has been given to the role of complement in disease. However, to better understand complement in pathology, it is crucial to first analyze this system under different physiological conditions. The aim of the present study was therefore to investigate the inter-individual variation in complement activity and the influences of age and sex.Methods: Complement levels and functional activity were determined in 120 healthy volunteers, 60 women, 60 men, age range 20–69 year. Serum functional activity of the classical pathway (CP), lectin pathway activated by mannan (MBL-LP) and alternative pathway (AP) was measured in sera, using deposition of C5b-9 as readout. In addition, levels of C1q, MBL, MASP-1, MASP-2, ficolin-2, ficolin-3, C2, C4, C3, C5, C6, C7, C8, C9, factor B, factor D, properdin, C1-inhibitor and C4b-binding protein, were determined. Age- and sex-related differences were evaluated.Results: Significantly lower AP activity was found in females compared to males. Further analysis of the AP revealed lower C3 and properdin levels in females, while factor D concentrations were higher. MBL-LP activity was not influenced by sex, but MBL and ficolin-3 levels were significantly lower in females compared to males. There were no significant differences in CP activity or CP components between females and males, nevertheless females had significantly lower levels of the terminal components. The CP and AP activity was significantly higher in the elderly, in contrast to MBL-LP activity. Moreover, C1-inhibitor, C5, C8, and C9 increased with age in contrast to a decrease of factor D and C3 levels. In-depth analysis of the functional activity assays revealed that MBL-LP activity was predominantly dependent on MBL and MASP-2 concentration, whereas CP activity relied on C2, C1-inhibitor and C5 levels. AP activity was strongly and directly associated with levels of C3, factor B and C5.Conclusion: This study demonstrated significant sex and age-related differences in complement levels and functionality in the healthy population. Therefore, age and sex analysis should be taken into consideration when discussing complement-related pathologies and subsequent complement-targeted therapies. |
| first_indexed | 2024-04-13T21:58:03Z |
| format | Article |
| id | doaj.art-1e14a85316cb4fc29fd7b3fea599874e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T21:58:03Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1e14a85316cb4fc29fd7b3fea599874e2022-12-22T02:28:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02664411472Age and Sex-Associated Changes of Complement Activity and Complement Levels in a Healthy Caucasian PopulationMariana Gaya da Costa0Felix Poppelaars1Felix Poppelaars2Cees van Kooten3Tom E. Mollnes4Tom E. Mollnes5Tom E. Mollnes6Francesco Tedesco7Reinhard Würzner8Leendert A. Trouw9Leendert A. Trouw10Lennart Truedsson11Mohamed R. Daha12Mohamed R. Daha13Anja Roos14Marc A. Seelen15Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDivision of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Obstetrics and Gynecology, Martini Hospital, Groningen, NetherlandsDepartment of Nephrology, University of Leiden, Leiden University Medical Center, Leiden, NetherlandsDepartment of Immunology, Oslo University Hospital and University of Oslo, Oslo, NorwayResearch Laboratory, Bodø Hospital, and K.G. Jebsen TREC, University of Tromsø, Tromsø, NorwayCentre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, NorwayImmunorheumatology Research Laboratory, Istituto Auxologico Italiano, IRCCS, Milan, ItalyDepartment of Hygiene, Microbiology and Public Health, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Rheumatology, Leiden University Medical Center, Leiden, Netherlands0Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands1Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University, Lund, SwedenDivision of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Nephrology, University of Leiden, Leiden University Medical Center, Leiden, Netherlands2Department of Medical Microbiology and Immunology, St. Antonius Hospital, Nieuwegein, NetherlandsDivision of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsIntroduction: The complement system is essential for an adequate immune response. Much attention has been given to the role of complement in disease. However, to better understand complement in pathology, it is crucial to first analyze this system under different physiological conditions. The aim of the present study was therefore to investigate the inter-individual variation in complement activity and the influences of age and sex.Methods: Complement levels and functional activity were determined in 120 healthy volunteers, 60 women, 60 men, age range 20–69 year. Serum functional activity of the classical pathway (CP), lectin pathway activated by mannan (MBL-LP) and alternative pathway (AP) was measured in sera, using deposition of C5b-9 as readout. In addition, levels of C1q, MBL, MASP-1, MASP-2, ficolin-2, ficolin-3, C2, C4, C3, C5, C6, C7, C8, C9, factor B, factor D, properdin, C1-inhibitor and C4b-binding protein, were determined. Age- and sex-related differences were evaluated.Results: Significantly lower AP activity was found in females compared to males. Further analysis of the AP revealed lower C3 and properdin levels in females, while factor D concentrations were higher. MBL-LP activity was not influenced by sex, but MBL and ficolin-3 levels were significantly lower in females compared to males. There were no significant differences in CP activity or CP components between females and males, nevertheless females had significantly lower levels of the terminal components. The CP and AP activity was significantly higher in the elderly, in contrast to MBL-LP activity. Moreover, C1-inhibitor, C5, C8, and C9 increased with age in contrast to a decrease of factor D and C3 levels. In-depth analysis of the functional activity assays revealed that MBL-LP activity was predominantly dependent on MBL and MASP-2 concentration, whereas CP activity relied on C2, C1-inhibitor and C5 levels. AP activity was strongly and directly associated with levels of C3, factor B and C5.Conclusion: This study demonstrated significant sex and age-related differences in complement levels and functionality in the healthy population. Therefore, age and sex analysis should be taken into consideration when discussing complement-related pathologies and subsequent complement-targeted therapies.https://www.frontiersin.org/article/10.3389/fimmu.2018.02664/fullcomplementhealthsex and ageinnate imunitygender |
| spellingShingle | Mariana Gaya da Costa Felix Poppelaars Felix Poppelaars Cees van Kooten Tom E. Mollnes Tom E. Mollnes Tom E. Mollnes Francesco Tedesco Reinhard Würzner Leendert A. Trouw Leendert A. Trouw Lennart Truedsson Mohamed R. Daha Mohamed R. Daha Anja Roos Marc A. Seelen Age and Sex-Associated Changes of Complement Activity and Complement Levels in a Healthy Caucasian Population Frontiers in Immunology complement health sex and age innate imunity gender |
| title | Age and Sex-Associated Changes of Complement Activity and Complement Levels in a Healthy Caucasian Population |
| title_full | Age and Sex-Associated Changes of Complement Activity and Complement Levels in a Healthy Caucasian Population |
| title_fullStr | Age and Sex-Associated Changes of Complement Activity and Complement Levels in a Healthy Caucasian Population |
| title_full_unstemmed | Age and Sex-Associated Changes of Complement Activity and Complement Levels in a Healthy Caucasian Population |
| title_short | Age and Sex-Associated Changes of Complement Activity and Complement Levels in a Healthy Caucasian Population |
| title_sort | age and sex associated changes of complement activity and complement levels in a healthy caucasian population |
| topic | complement health sex and age innate imunity gender |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02664/full |
| work_keys_str_mv | AT marianagayadacosta ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT felixpoppelaars ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT felixpoppelaars ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT ceesvankooten ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT tomemollnes ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT tomemollnes ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT tomemollnes ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT francescotedesco ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT reinhardwurzner ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT leendertatrouw ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT leendertatrouw ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT lennarttruedsson ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT mohamedrdaha ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT mohamedrdaha ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT anjaroos ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation AT marcaseelen ageandsexassociatedchangesofcomplementactivityandcomplementlevelsinahealthycaucasianpopulation |