Complement factor H Y402H polymorphism results in diminishing CD4+T cells and increasing C-reactive protein in plasma.

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Standard

Complement factor H Y402H polymorphism results in diminishing CD4+T cells and increasing C-reactive protein in plasma. / Nielsen, Marie Krogh; Subhi, Yousif; Falk, Mads; Singh, Amardeep; Sørensen, Torben Lykke; Nissen, Mogens Holst; Faber, Carsten.

I: Scientific Reports, Bind 13, Nr. 1, 19414, 08.11.2023.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Nielsen, MK, Subhi, Y, Falk, M, Singh, A, Sørensen, TL, Nissen, MH & Faber, C 2023, 'Complement factor H Y402H polymorphism results in diminishing CD4+T cells and increasing C-reactive protein in plasma.', Scientific Reports, bind 13, nr. 1, 19414. https://doi.org/10.1038/s41598-023-46827-0

APA

Nielsen, M. K., Subhi, Y., Falk, M., Singh, A., Sørensen, T. L., Nissen, M. H., & Faber, C. (2023). Complement factor H Y402H polymorphism results in diminishing CD4+T cells and increasing C-reactive protein in plasma. Scientific Reports, 13(1), [19414]. https://doi.org/10.1038/s41598-023-46827-0

Vancouver

Nielsen MK, Subhi Y, Falk M, Singh A, Sørensen TL, Nissen MH o.a. Complement factor H Y402H polymorphism results in diminishing CD4+T cells and increasing C-reactive protein in plasma. Scientific Reports. 2023 nov. 8;13(1). 19414. https://doi.org/10.1038/s41598-023-46827-0

Author

Nielsen, Marie Krogh ; Subhi, Yousif ; Falk, Mads ; Singh, Amardeep ; Sørensen, Torben Lykke ; Nissen, Mogens Holst ; Faber, Carsten. / Complement factor H Y402H polymorphism results in diminishing CD4+T cells and increasing C-reactive protein in plasma. I: Scientific Reports. 2023 ; Bind 13, Nr. 1.

Bibtex

@article{42f3b5d65e9b4d5c8a1e18d3be7112cf,
title = "Complement factor H Y402H polymorphism results in diminishing CD4+T cells and increasing C-reactive protein in plasma.",
abstract = "Age-related macular degeneration (AMD) is a common cause of visual loss among the elderly. Genetic variants in the gene encoding complement factor H (CFH) have been identified as an AMD susceptibility gene, however, the mechanistic link is debated. Here, we investigated the link between the CFH Y402H genotype and low-grade inflammation. We recruited 153 healthy individuals, 84 participants with dry stages of AMD, and 148 participants with neovascular AMD. All participants were subjected to detailed retinal examination, and interview regarding comorbidities and lifestyle. Blood samples were analyzed for level of C-Reactive Protein (CRP), white blood cell differential count, and stained with fluorescent antibodies to differentiate CD4 + and CD8 + T cells. CFH Y402H genotyping was performed using an allele-specific polymerase chain reaction genotyping assay. Splenocytes from young and aged wild type and Cfh null mutant C57BL/6J mice were examined for CD4 + and CD8 + T cells. Healthy individuals with the CFH Y402H at-risk polymorphism HH had higher levels of CRP and lower proportions of CD4 + T cells compared to persons with the YH or YY polymorphism (P = 0.037, Chi-square). Healthy individuals with the HH polymorphism displayed lower proportions of CD4 + T cells with ageing (P < 0.01, one-way ANOVA), whereas both young and aged Cfh null mutant mice displayed lower proportions of CD4 + T cells (P < 0.001 and P < 0.05; unpaired t test). Participants with dry AMD and the HH polymorphism had similarly lower proportions of CD4 + T cells (P = 0.024, one-way ANOVA), but no difference in CRP-levels. In the neovascular stage of AMD, there was no difference in proportion of CD4 + cells or CRP levels according to genotype. The risk-associated CFH genotype is associated with an age-related decrease in proportion of CD4 + T cells and increased levels of CRP in healthy individuals. This indicates that decreased complement regulation results in extensive changes in innate and adaptive immune compartments that precede development of AMD. ",
keywords = "Aged, Mice, Animals, Humans, C-Reactive Protein/metabolism, Complement Factor H/genetics, CD8-Positive T-Lymphocytes/metabolism, Angiogenesis Inhibitors, Polymorphism, Single Nucleotide, Mice, Inbred C57BL, Visual Acuity, Vascular Endothelial Growth Factor A/genetics, Wet Macular Degeneration, Genotype, CD4-Positive T-Lymphocytes/metabolism, Case-Control Studies",
author = "Nielsen, {Marie Krogh} and Yousif Subhi and Mads Falk and Amardeep Singh and S{\o}rensen, {Torben Lykke} and Nissen, {Mogens Holst} and Carsten Faber",
note = "{\textcopyright} 2023. The Author(s).",
year = "2023",
month = nov,
day = "8",
doi = "10.1038/s41598-023-46827-0",
language = "English",
volume = "13",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Complement factor H Y402H polymorphism results in diminishing CD4+T cells and increasing C-reactive protein in plasma.

AU - Nielsen, Marie Krogh

AU - Subhi, Yousif

AU - Falk, Mads

AU - Singh, Amardeep

AU - Sørensen, Torben Lykke

AU - Nissen, Mogens Holst

AU - Faber, Carsten

N1 - © 2023. The Author(s).

PY - 2023/11/8

Y1 - 2023/11/8

N2 - Age-related macular degeneration (AMD) is a common cause of visual loss among the elderly. Genetic variants in the gene encoding complement factor H (CFH) have been identified as an AMD susceptibility gene, however, the mechanistic link is debated. Here, we investigated the link between the CFH Y402H genotype and low-grade inflammation. We recruited 153 healthy individuals, 84 participants with dry stages of AMD, and 148 participants with neovascular AMD. All participants were subjected to detailed retinal examination, and interview regarding comorbidities and lifestyle. Blood samples were analyzed for level of C-Reactive Protein (CRP), white blood cell differential count, and stained with fluorescent antibodies to differentiate CD4 + and CD8 + T cells. CFH Y402H genotyping was performed using an allele-specific polymerase chain reaction genotyping assay. Splenocytes from young and aged wild type and Cfh null mutant C57BL/6J mice were examined for CD4 + and CD8 + T cells. Healthy individuals with the CFH Y402H at-risk polymorphism HH had higher levels of CRP and lower proportions of CD4 + T cells compared to persons with the YH or YY polymorphism (P = 0.037, Chi-square). Healthy individuals with the HH polymorphism displayed lower proportions of CD4 + T cells with ageing (P < 0.01, one-way ANOVA), whereas both young and aged Cfh null mutant mice displayed lower proportions of CD4 + T cells (P < 0.001 and P < 0.05; unpaired t test). Participants with dry AMD and the HH polymorphism had similarly lower proportions of CD4 + T cells (P = 0.024, one-way ANOVA), but no difference in CRP-levels. In the neovascular stage of AMD, there was no difference in proportion of CD4 + cells or CRP levels according to genotype. The risk-associated CFH genotype is associated with an age-related decrease in proportion of CD4 + T cells and increased levels of CRP in healthy individuals. This indicates that decreased complement regulation results in extensive changes in innate and adaptive immune compartments that precede development of AMD.

AB - Age-related macular degeneration (AMD) is a common cause of visual loss among the elderly. Genetic variants in the gene encoding complement factor H (CFH) have been identified as an AMD susceptibility gene, however, the mechanistic link is debated. Here, we investigated the link between the CFH Y402H genotype and low-grade inflammation. We recruited 153 healthy individuals, 84 participants with dry stages of AMD, and 148 participants with neovascular AMD. All participants were subjected to detailed retinal examination, and interview regarding comorbidities and lifestyle. Blood samples were analyzed for level of C-Reactive Protein (CRP), white blood cell differential count, and stained with fluorescent antibodies to differentiate CD4 + and CD8 + T cells. CFH Y402H genotyping was performed using an allele-specific polymerase chain reaction genotyping assay. Splenocytes from young and aged wild type and Cfh null mutant C57BL/6J mice were examined for CD4 + and CD8 + T cells. Healthy individuals with the CFH Y402H at-risk polymorphism HH had higher levels of CRP and lower proportions of CD4 + T cells compared to persons with the YH or YY polymorphism (P = 0.037, Chi-square). Healthy individuals with the HH polymorphism displayed lower proportions of CD4 + T cells with ageing (P < 0.01, one-way ANOVA), whereas both young and aged Cfh null mutant mice displayed lower proportions of CD4 + T cells (P < 0.001 and P < 0.05; unpaired t test). Participants with dry AMD and the HH polymorphism had similarly lower proportions of CD4 + T cells (P = 0.024, one-way ANOVA), but no difference in CRP-levels. In the neovascular stage of AMD, there was no difference in proportion of CD4 + cells or CRP levels according to genotype. The risk-associated CFH genotype is associated with an age-related decrease in proportion of CD4 + T cells and increased levels of CRP in healthy individuals. This indicates that decreased complement regulation results in extensive changes in innate and adaptive immune compartments that precede development of AMD.

KW - Aged

KW - Mice

KW - Animals

KW - Humans

KW - C-Reactive Protein/metabolism

KW - Complement Factor H/genetics

KW - CD8-Positive T-Lymphocytes/metabolism

KW - Angiogenesis Inhibitors

KW - Polymorphism, Single Nucleotide

KW - Mice, Inbred C57BL

KW - Visual Acuity

KW - Vascular Endothelial Growth Factor A/genetics

KW - Wet Macular Degeneration

KW - Genotype

KW - CD4-Positive T-Lymphocytes/metabolism

KW - Case-Control Studies

U2 - 10.1038/s41598-023-46827-0

DO - 10.1038/s41598-023-46827-0

M3 - Journal article

C2 - 37940659

VL - 13

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 19414

ER -

ID: 372801809