دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Complement factor H Y402H polymorphism results in diminishing CD4 + T cells and increasing C-reactive protein in plasma.
المؤلفون: Nielsen MK; Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark., Subhi Y; Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, Denmark.; Department of Clinical Research, University of Southern Denmark, Odense, Denmark., Falk M; Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark., Singh A; Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Sørensen TL; Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Nissen MH; Department of Immunology and Microbiology, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark., Faber C; Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, Denmark. carstenfaber@gmail.com.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. carstenfaber@gmail.com.
المصدر: Scientific reports [Sci Rep] 2023 Nov 08; Vol. 13 (1), pp. 19414. Date of Electronic Publication: 2023 Nov 08.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: C-Reactive Protein*/metabolism , Wet Macular Degeneration*, Aged ; Mice ; Animals ; Humans ; Complement Factor H/genetics ; Complement Factor H/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Angiogenesis Inhibitors ; Polymorphism, Single Nucleotide ; Mice, Inbred C57BL ; Visual Acuity ; Vascular Endothelial Growth Factor A/genetics ; Genotype ; CD4-Positive T-Lymphocytes/metabolism ; Case-Control Studies
مستخلص: 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.
(© 2023. The Author(s).)
References: Immunol Lett. 2015 Apr;164(2):117-24. (PMID: 25742728)
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17456-61. (PMID: 17079491)
PLoS One. 2008 Jul 02;3(7):e2593. (PMID: 18596911)
Mech Ageing Dev. 2020 Oct;191:111353. (PMID: 32937187)
Aging (Albany NY). 2017 Nov 20;9(11):2436-2452. (PMID: 29165313)
Sci Rep. 2016 Mar 10;6:22889. (PMID: 26961257)
Immunol Rev. 2023 Jan;313(1):279-297. (PMID: 36223117)
Nat Rev Immunol. 2013 Jun;13(6):438-51. (PMID: 23702979)
Nat Genet. 2002 Aug;31(4):424-8. (PMID: 12091909)
Invest Ophthalmol Vis Sci. 2019 Jan 2;60(1):192-201. (PMID: 30654385)
J Immunol. 2007 Mar 15;178(6):3831-6. (PMID: 17339482)
Avicenna J Med. 2013 Apr;3(2):37-47. (PMID: 23930241)
JAMA. 2006 Jul 19;296(3):301-9. (PMID: 16849663)
Am J Ophthalmol. 2013 Dec;156(6):1176-83. (PMID: 24083687)
Am J Ophthalmol. 2013 Jan;155(1):1-35.e13. (PMID: 23245386)
Ophthalmology. 2012 Feb;119(2):339-46. (PMID: 22133792)
Immun Ageing. 2019 Aug 15;16:20. (PMID: 31428180)
Acta Ophthalmol. 2019 Sep;97(6):558-566. (PMID: 30811869)
Am J Ophthalmol. 2017 Jul;179:151-158. (PMID: 28499708)
Cell Mol Life Sci. 2020 Mar;77(5):781-788. (PMID: 31897541)
Nat Immunol. 2017 Nov 16;18(12):1288-1298. (PMID: 29144501)
Clin Exp Ophthalmol. 2019 Jan;47(1):69-78. (PMID: 30047199)
Prog Retin Eye Res. 2020 May;76:100825. (PMID: 31899290)
Nat Rev Immunol. 2007 Jan;7(1):9-18. (PMID: 17170757)
Gerontology. 2009;55(3):314-21. (PMID: 19190395)
Invest Ophthalmol Vis Sci. 2009 Dec;50(12):5818-27. (PMID: 19661236)
Biogerontology. 2008 Oct;9(5):299-308. (PMID: 18369735)
Exp Eye Res. 2011 Mar;92(3):180-8. (PMID: 21255569)
Ophthalmology. 2006 Feb;113(2):260-6. (PMID: 16458093)
Immun Ageing. 2017 Jul 27;14:18. (PMID: 28769990)
Exp Eye Res. 2022 May;218:108982. (PMID: 35183540)
Exp Gerontol. 2007 Nov;42(11):1116-22. (PMID: 17869048)
Surv Ophthalmol. 2011 May-Jun;56(3):184-94. (PMID: 21420705)
Invest Ophthalmol Vis Sci. 2019 Jan 2;60(1):202-208. (PMID: 30644965)
Ophthalmology. 2013 Nov;120(11):2310-6. (PMID: 23747161)
المشرفين على المادة: 9007-41-4 (C-Reactive Protein)
80295-65-4 (Complement Factor H)
0 (Angiogenesis Inhibitors)
0 (Vascular Endothelial Growth Factor A)
تواريخ الأحداث: Date Created: 20231108 Date Completed: 20231110 Latest Revision: 20231111
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10632322
DOI: 10.1038/s41598-023-46827-0
PMID: 37940659
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-023-46827-0