The Interaction Between Allelic Variants of CD86 and CD40LG: A Common Risk Factor of Allergic Asthma and Rheumatoid Arthritis

Overview

Journal Allergy Asthma Immunol Res

Date 2014 Mar 4

PMID 24587950

Citations 16

Authors

So-Hee Lee

Eun-Bong Lee

Eun-Soon Shin

Jong-Eun Lee

Sang-Heon Cho

Kyung-Up Min

Heung-Woo Park

Affiliations

Soon will be listed here.

Abstract

Purpose: Allergic asthma (AA) and rheumatoid arthritis (RA) are immune tolerance-related diseases, and immune tolerance is known to be influenced by costimulatory molecules. In this study, we sought to identify common genetic susceptibility in AA and RA.

Methods: Two hundred cases of AA, 184 cases of RA, and 182 healthy controls were recruited at the Seoul National University Hospital, Seoul, Korea. Eight single nucleotide polymorphisms (SNPs) in five genes coding costimulatory molecules, namely, -318C>T, +49A>G, and 6230G>A in CTLA4, IVS3+17T>C in CD28, -3479T>G and I179V in CD86, -1C>T in CD40, and -3458A>G in CD40LG were scored, and genetic interactions were evaluated by multifactor dimensionality reduction (MDR) analysis.

Results: MDR analysis revealed a significant gene-gene interaction between -3479T>G CD86 and -3458A>G CD40LG for AA. Subjects with the T/T genotype of -3479T>G CD86 and the A/A genotype of -3458A>G CD40LG were found to be significantly more likely to develop AA than those with the T/T genotype of -3479T>G CD86 and A/- genotype of -3458A>G CD40LG (adjusted OR, 6.09; 95% CI, 2.89-12.98; logistic regression analysis controlled by age). Similarly those subjects showed a significant risk of developing RA (adjusted OR, 39.35; 95% CI, 15.01-107.00, logistic regression analysis controlled by age).

Conclusions: Our findings suggest that a genetic interaction between CD86 and CD40LG favors the development of both AA and RA.

Citing Articles

Establishment of a diagnostic model based on immune-related genes in children with asthma.

Yuan Y, Zhu H, Huang S, Zhang Y, Shen Y Heliyon. 2024; 10(4):e25735.

PMID: 38375253 PMC: 10875436. DOI: 10.1016/j.heliyon.2024.e25735.

Asthma and atopic dermatitis as risk factors for rheumatoid arthritis: a bidirectional mendelian randomization study.

Chen C, Su L, Duan W, Zheng Y, Zhang D, Wang Y BMC Med Genomics. 2023; 16(1):41.

PMID: 36869337 PMC: 9985208. DOI: 10.1186/s12920-023-01461-7.

Clinical features of asthma with connective tissue diseases.

Watanabe K, Horita N, Hara Y, Kobayashi N, Kaneko T Clin Respir J. 2023; 17(4):303-310.

PMID: 36806936 PMC: 10113276. DOI: 10.1111/crj.13595.

Allergic conditions and risk of rheumatoid arthritis: a Swedish case-control study.

Kronzer V, Westerlind H, Alfredsson L, Crowson C, Klareskog L, Holmqvist M RMD Open. 2022; 8(1).

PMID: 35168998 PMC: 8852704. DOI: 10.1136/rmdopen-2021-002018.

Genetic variations in the and proteasome genes are associated with multiple sclerosis and response to interferon-β therapy in Latvians.

Paramonova N, Kalnina J, Dokane K, Dislere K, Trapina I, Sjakste T Exp Ther Med. 2021; 21(5):478.

PMID: 33767773 PMC: 7976443. DOI: 10.3892/etm.2021.9909.

References

Balada E, Castro-Marrero J, Felip L, Ordi-Ros J, Vilardell-Tarres M . Associations between the expression of epigenetically regulated genes and the expression of DNMTs and MBDs in systemic lupus erythematosus. PLoS One. 2012; 7(9):e45897. PMC: 3448686. DOI: 10.1371/journal.pone.0045897. View

Lafferty K, Cunningham A . A new analysis of allogeneic interactions. Aust J Exp Biol Med Sci. 1975; 53(1):27-42. DOI: 10.1038/icb.1975.3. View

Oxenius A, Campbell K, Maliszewski C, Kishimoto T, Kikutani H, Hengartner H . CD40-CD40 ligand interactions are critical in T-B cooperation but not for other anti-viral CD4+ T cell functions. J Exp Med. 1996; 183(5):2209-18. PMC: 2192545. DOI: 10.1084/jem.183.5.2209. View

Motsinger A, Ritchie M, Reif D . Novel methods for detecting epistasis in pharmacogenomics studies. Pharmacogenomics. 2007; 8(9):1229-41. DOI: 10.2217/14622416.8.9.1229. View

Clayton D . Sex chromosomes and genetic association studies. Genome Med. 2009; 1(11):110. PMC: 2808745. DOI: 10.1186/gm110. View

Borrow P, Tishon A, Lee S, Xu J, Grewal I, Oldstone M . CD40L-deficient mice show deficits in antiviral immunity and have an impaired memory CD8+ CTL response. J Exp Med. 1996; 183(5):2129-42. PMC: 2192549. DOI: 10.1084/jem.183.5.2129. View

Clayton D . Testing for association on the X chromosome. Biostatistics. 2008; 9(4):593-600. PMC: 2536723. DOI: 10.1093/biostatistics/kxn007. View

Lombardi V, Singh A, Akbari O . The role of costimulatory molecules in allergic disease and asthma. Int Arch Allergy Immunol. 2009; 151(3):179-89. PMC: 2837887. DOI: 10.1159/000242355. View

Chattopadhyay K, Lazar-Molnar E, Yan Q, Rubinstein R, Zhan C, Vigdorovich V . Sequence, structure, function, immunity: structural genomics of costimulation. Immunol Rev. 2009; 229(1):356-86. PMC: 3001128. DOI: 10.1111/j.1600-065X.2009.00778.x. View

10.

Arnett F, Edworthy S, Bloch D, McShane D, Fries J, Cooper N . The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31(3):315-24. DOI: 10.1002/art.1780310302. View

11.

Akdis M, Akdis C . Therapeutic manipulation of immune tolerance in allergic disease. Nat Rev Drug Discov. 2009; 8(8):645-60. DOI: 10.1038/nrd2653. View

12.

Simpson C, Anderson W, Helms P, Taylor M, Watson L, Prescott G . Coincidence of immune-mediated diseases driven by Th1 and Th2 subsets suggests a common aetiology. A population-based study using computerized general practice data. Clin Exp Allergy. 2002; 32(1):37-42. DOI: 10.1046/j.0022-0477.2001.01250.x. View

13.

Suzuki M, Zheng X, Zhang X, Ichim T, Sun H, Kubo N . Inhibition of allergic responses by CD40 gene silencing. Allergy. 2009; 64(3):387-97. DOI: 10.1111/j.1398-9995.2008.01839.x. View

14.

Kawabe T, Naka T, Yoshida K, Tanaka T, Fujiwara H, Suematsu S . The immune responses in CD40-deficient mice: impaired immunoglobulin class switching and germinal center formation. Immunity. 1994; 1(3):167-78. DOI: 10.1016/1074-7613(94)90095-7. View

15.

Goronzy J, Weyand C . T-cell regulation in rheumatoid arthritis. Curr Opin Rheumatol. 2004; 16(3):212-7. DOI: 10.1097/00002281-200405000-00008. View

16.

Bosse Y, Lemire M, Poon A, Daley D, He J, Sandford A . Asthma and genes encoding components of the vitamin D pathway. Respir Res. 2009; 10:98. PMC: 2779188. DOI: 10.1186/1465-9921-10-98. View

17.

Eshima K, Choi Y, Flavell R . CD154-CD40-independent up-regulation of B7-2 on splenic antigen-presenting cells and efficient T cell priming by staphylococcal enterotoxin A. Int Immunol. 2003; 15(7):817-26. DOI: 10.1093/intimm/dxg080. View

18.

Grewal I, Xu J, Flavell R . Impairment of antigen-specific T-cell priming in mice lacking CD40 ligand. Nature. 1995; 378(6557):617-20. DOI: 10.1038/378617a0. View

19.

Boyle A, Hong E, Hariharan M, Cheng Y, Schaub M, Kasowski M . Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 2012; 22(9):1790-7. PMC: 3431494. DOI: 10.1101/gr.137323.112. View

20.

Hahn L, Ritchie M, Moore J . Multifactor dimensionality reduction software for detecting gene-gene and gene-environment interactions. Bioinformatics. 2003; 19(3):376-82. DOI: 10.1093/bioinformatics/btf869. View