Common Haplotypes within the Chromosome 1q31.3 Region Determine Systemic Concentrations of the Entire Complement Factor H Protein Family
Introduction: The alternative pathway of complement activation is consistently active, keeping the complement system primed for immediate response. This constant “tick-over” mechanism is regulated by the factor H (FH) protein family, which encompasses seven highly related proteins: FH, FH...
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| Format: | Article |
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Karger Publishers
2025-01-01
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| Series: | Journal of Innate Immunity |
| Online Access: | https://karger.com/article/doi/10.1159/000545342 |
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| author | Bert R.J. Veuskens Mara van Rossum Emi Cattenstart Mieke C. Brouwer Gerard van Mierlo Judy Geissler Karin van Leeuwen Jin Liu Robert A. Anstadt Burt T. Richards Gregory S. Hageman Taco W. Kuijpers Erik J.M. Toonen Richard B. Pouw |
| author_facet | Bert R.J. Veuskens Mara van Rossum Emi Cattenstart Mieke C. Brouwer Gerard van Mierlo Judy Geissler Karin van Leeuwen Jin Liu Robert A. Anstadt Burt T. Richards Gregory S. Hageman Taco W. Kuijpers Erik J.M. Toonen Richard B. Pouw |
| author_sort | Bert R.J. Veuskens |
| collection | DOAJ |
| description |
Introduction: The alternative pathway of complement activation is consistently active, keeping the complement system primed for immediate response. This constant “tick-over” mechanism is regulated by the factor H (FH) protein family, which encompasses seven highly related proteins: FH, FHL-1, and five FH-related (FHR-1 to -5) proteins. The current model is that the FHRs compete with FH and FHL-1 to fine-tune their activities. Genetic studies of this complex locus have revealed distinct haplotypes associating with a wide array of human diseases, underscoring its significant role in complement regulation. Nevertheless, a comprehensive analysis of systemic concentrations of all FH protein family members, accounting for known genetic variability within the population, is still lacking. Methods: Systemic levels of each member of the FH protein family were quantified with the use of recently developed target specific ELISAs. Next, a genetic analysis focused on the chromosome 1q31.3 region was performed using next generation sequencing and multiplex ligase probe-dependent amplification. Results: We report systemic protein levels of each member of the FH protein family found in vivo and demonstrate common haplotypes within the CFH locus give rise to classifiable protein expression patterns, establishing distinct ratios between FH, FHL-1, and the FHRs. Conclusions: The established reference intervals and identified genetic effects provide a benchmark for further research and emphasize the importance of including all family members when studying their role in both health and disease. |
| format | Article |
| id | doaj-art-e8d597c4f45847b0a195b84d2aa39e18 |
| institution | OA Journals |
| issn | 1662-8128 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Journal of Innate Immunity |
| spelling | doaj-art-e8d597c4f45847b0a195b84d2aa39e182025-08-20T02:31:55ZengKarger PublishersJournal of Innate Immunity1662-81282025-01-0117124426110.1159/000545342Common Haplotypes within the Chromosome 1q31.3 Region Determine Systemic Concentrations of the Entire Complement Factor H Protein FamilyBert R.J. VeuskensMara van RossumEmi CattenstartMieke C. BrouwerGerard van MierloJudy GeisslerKarin van LeeuwenJin LiuRobert A. AnstadtBurt T. RichardsGregory S. HagemanTaco W. KuijpersErik J.M. ToonenRichard B. Pouw Introduction: The alternative pathway of complement activation is consistently active, keeping the complement system primed for immediate response. This constant “tick-over” mechanism is regulated by the factor H (FH) protein family, which encompasses seven highly related proteins: FH, FHL-1, and five FH-related (FHR-1 to -5) proteins. The current model is that the FHRs compete with FH and FHL-1 to fine-tune their activities. Genetic studies of this complex locus have revealed distinct haplotypes associating with a wide array of human diseases, underscoring its significant role in complement regulation. Nevertheless, a comprehensive analysis of systemic concentrations of all FH protein family members, accounting for known genetic variability within the population, is still lacking. Methods: Systemic levels of each member of the FH protein family were quantified with the use of recently developed target specific ELISAs. Next, a genetic analysis focused on the chromosome 1q31.3 region was performed using next generation sequencing and multiplex ligase probe-dependent amplification. Results: We report systemic protein levels of each member of the FH protein family found in vivo and demonstrate common haplotypes within the CFH locus give rise to classifiable protein expression patterns, establishing distinct ratios between FH, FHL-1, and the FHRs. Conclusions: The established reference intervals and identified genetic effects provide a benchmark for further research and emphasize the importance of including all family members when studying their role in both health and disease. https://karger.com/article/doi/10.1159/000545342 |
| spellingShingle | Bert R.J. Veuskens Mara van Rossum Emi Cattenstart Mieke C. Brouwer Gerard van Mierlo Judy Geissler Karin van Leeuwen Jin Liu Robert A. Anstadt Burt T. Richards Gregory S. Hageman Taco W. Kuijpers Erik J.M. Toonen Richard B. Pouw Common Haplotypes within the Chromosome 1q31.3 Region Determine Systemic Concentrations of the Entire Complement Factor H Protein Family Journal of Innate Immunity |
| title | Common Haplotypes within the Chromosome 1q31.3 Region Determine Systemic Concentrations of the Entire Complement Factor H Protein Family |
| title_full | Common Haplotypes within the Chromosome 1q31.3 Region Determine Systemic Concentrations of the Entire Complement Factor H Protein Family |
| title_fullStr | Common Haplotypes within the Chromosome 1q31.3 Region Determine Systemic Concentrations of the Entire Complement Factor H Protein Family |
| title_full_unstemmed | Common Haplotypes within the Chromosome 1q31.3 Region Determine Systemic Concentrations of the Entire Complement Factor H Protein Family |
| title_short | Common Haplotypes within the Chromosome 1q31.3 Region Determine Systemic Concentrations of the Entire Complement Factor H Protein Family |
| title_sort | common haplotypes within the chromosome 1q31 3 region determine systemic concentrations of the entire complement factor h protein family |
| url | https://karger.com/article/doi/10.1159/000545342 |
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