Association between CD40 polymorphisms and systemic lupus erythematosus and correlation between soluble CD40 and CD40 ligand levels in the disease: a meta-analysis

Abstract

Objective

The aim of this study was to systematically review evidence regarding the association between CD40 polymorphisms and systemic lupus erythematosus and between soluble CD40 (sCD40) and CD40 ligand (sCD40L) levels and systemic lupus erythematosus.

Methods

We performed a meta-analysis on the association between CD40 rs4810495, rs1883832, and rs376545 polymorphisms and systemic lupus erythematosus risk and sCD40/sCD40L levels in patients with systemic lupus erythematosus and controls.

Results

Fourteen studies were included. Ethnicity-specific meta-analysis indicated a significant association between the T allele of CD40 rs4810485 polymorphism and systemic lupus erythematosus in Europeans (odds ratio = 0.715, 95% confidence interval = 0.641–0.832, p < 0.001) and a trend toward an association between the T allele and systemic lupus erythematosus in Asians (odds ratio = 1.255, 95% confidence interval = 0.978–1.810, p = 0.074). Furthermore, a significant association was reported between systemic lupus erythematosus and the C allele of CD40 rs1883832 polymorphism (odds ratio = 1.235, 95% confidence interval = 1.087–1.405, p = 0.001) and A allele of CD40 rs3765456 polymorphism and systemic lupus erythematosus in Asians (odds ratio = 1.184, 95% confidence interval = 1.040–1.348, p = 0.011). sCD40 and sCD40L levels were significantly higher in SLE than in controls (standardized mean difference = 1.564, 95% confidence interval = 0.256–2.872, p = 0.019 and standardized mean difference = 1.499, 95% confidence interval = 1.031–1.967, p < 0.001, respectively). Stratification based on ethnicity revealed higher sCD40L levels in the systemic lupus erythematosus group among European, Asian, North American, and Arab populations.

Conclusions

Our meta-analyses found associations between CD40 rs4810495, rs1883832, and rs376545 polymorphisms and systemic lupus erythematosus susceptibility and significantly higher sCD40 and sCD40L levels in patients with systemic lupus erythematosus than in controls.

Keywords

CD40 polymorphism level systemic lupus erythematosus

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References

Ruiz-Irastorza

Khamashta

Castellino

Hughes

. Systemic lupus erythematosus. Lancet 2001; 357: 1027–1032.

Kotzin

. Systemic lupus erythematosus. Cell 1996; 85: 303–306.

Lee

Bae

S-C

Choi

Song

. Genome-wide pathway analysis of genome-wide association studies on systemic lupus erythematosus and rheumatoid arthritis. Mol Biol Rep 2012; 39: 10627–10635.

Schonbeck

Libby

. The CD40/CD154 receptor/ligand dyad. Cell Mol Life Sci 2001; 58: 4–43.

Peters

Stunz

Bishop

. CD40 and autoimmunity: the dark side of a great activator. Semin Immunol 2009; 21: 293–300.

Gaffney

Ortmann

Selby

, et al. Genome screening in human systemic lupus erythematosus: results from a second Minnesota cohort and combined analyses of 187 sib-pair families. Am J Hum Genet 2000; 66: 547–556.

Vazgiourakis

Zervou

Choulaki

, et al. A common SNP in the CD40 region is associated with systemic lupus erythematosus and correlates with altered CD40 expression: implications for the pathogenesis. Ann Rheum Dis 2011; 70: 2184–2190.

Mousa

Omar

Emad

, et al. The association of CD40 polymorphism (rs1883832C/T) and soluble CD40 with the risk of systemic lupus erythematosus among Egyptian patients. Clin Rheumatol 2019; 38: 777–784.

Nie

Yan

Wang

Zhou

. Gene-gene interaction between CD40 and CD226 gene on systemic lupus erythematosus in the Chinese Han population. Rheumatol Int 2016; 36: 1657–1662.

10.

Chen

Guo

Wei

, et al. The association of CD40 polymorphisms with CD40 serum levels and risk of systemic lupus erythematosus. BMC Genet 2015; 16: 121–121.

11.

Piotrowski

Lianeri

Wudarski

Olesinska

Jagodzinski

. Single nucleotide polymorphism of CD40 region and the risk of systemic lupus erythematosus. Lupus 2013; 22: 233–237.

12.

Joo

Park

Shin

Park

Kim

Bae

. Association of genetic polymorphisms in CD40 with susceptibility to SLE in the Korean population. Rheumatology (Oxford) 2013; 52: 623–630.

13.

Xiang

Guo

Peng

Huang

Lan

Wei

. Association study of CD154 polymorphisms and serum CD154 level with systemic lupus erythematous in Chinese population. Rheumatol Int 2017; 37: 1287–1294.

14.

Kim

Baek

Yoon

Kim

Cho

. Elevated levels of soluble CD40 ligand are associated with antiphospholipid antibodies in patients with systemic lupus erythematosus. Clin Exp Rheumatol 2017; 35: 823–830.

15.

Sellam

Proulle

Jungel

, et al. Increased levels of circulating microparticles in primary Sjogren’s syndrome, systemic lupus erythematosus and rheumatoid arthritis and relation with disease activity. Arthritis Res Ther 2009; 11: R156–R156.

16.

ElGendi

El-Sherif

. Anti-C1q antibodies, sCD40L, TWEAK and CD4/CD8 ratio in systemic lupus erythematosus and their relations to disease activity and renal involvement. Egypt J Immunol 2009; 16: 135–148.

17.

Ciferska

Horak

Hermanova

, et al. The levels of sCD30 and of sCD40L in a group of patients with systemic lupus erythematodes and their diagnostic value. Clin Rheumatol 2007; 26: 723–728.

18.

Goules

Tzioufas

Manousakis

Kirou

Crow

Routsias

. Elevated levels of soluble CD40 ligand (sCD40L) in serum of patients with systemic autoimmune diseases. J Autoimmun 2006; 26: 165–171.

19.

Ferro

Pignatelli

Loffredo

, et al. Soluble CD154 plasma levels in patients with systemic lupus erythematosus: modulation by antiphospholipid antibodies. Arthritis Rheum 2004; 50: 1693–1694.

20.

Vakkalanka

Woo

Kirou

Koshy

Berger

Crow

. Elevated levels and functional capacity of soluble CD40 ligand in systemic lupus erythematosus sera. Arthritis Rheum 1999; 42: 871–881.

21.

Lee

Bae

S-C

Choi

Song

. Associations between TNFAIP3 gene polymorphisms and rheumatoid arthritis: a meta-analysis. Inflammation Res 2012; 61: 635–641.

22.

Lee

Bae

Song

. Hepatitis B virus reactivation in HBsAg-positive patients with rheumatic diseases undergoing anti-tumor necrosis factor therapy or DMARDs. Int J Rheum Dis 2013; 16: 527–531.

23.

Lee

Song

. Comparative efficacy and safety of secukinumab and adalimumab in patients with active ankylosing spondylitis: a Bayesian network meta-analysis of randomized controlled trials. J Rheum Dis 2017; 24: 211–219.

24.

Moher

Liberati

Tetzlaff

, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: e1000097–e1000097.

25.

Hozo

Djulbegovic

Hozo

. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005; 5: 13–13.

26.

Ridout

Price

Sen

Tyrka

. Depression and telomere length: A meta-analysis. J Affective Disord 2016; 191: 237–247.

27.

Higgins

Thompson

. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539–1558.

28.

DerSimonian

Laird

. Meta-analysis in clinical trials. Controlled Clin Trials 1986; 7: 177–188.

29.

Egger

Davey Smith

Schneider

Minder

. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–634.

30.

Guo

Luo

, et al. Association of CD40 polymorphisms and haplotype with risk of systemic lupus erythematosus. Rheumatol Int 2016; 36: 45–52.

31.

Chadha

Miller

Farwell

, et al. Haplotype structure of TNFRSF5-TNFSF5 (CD40-CD40L) and association analysis in systemic lupus erythematosus. Eur J Hum Genet 2005; 13: 669–676.

32.

Popkova

Panafidina

Aleksandrova

, et al. [Soluble CD40 ligand in systemic lupus erythematosus: link with atherosclerotic vascular affection]. Ter Arkh 2008; 80: 37–41.

33.

Aleksandrova

Novikov

Popkova

, et al. [Soluble CD40 ligand in systemic lupus erythematosus and antiphospholipid syndrome]. Ter Arkh 2006; 78: 35–39.

34.

Rizvi

Pathak

Freedman

Chakrabarti

. CD40-CD40 ligand interactions in oxidative stress, inflammation and vascular disease. Trends Mol Med 2008; 14: 530–538.

35.

Kawabe

Naka

Yoshida

, et al. The immune responses in CD40-deficient mice: impaired immunoglobulin class switching and germinal center formation. Immunity 1994; 1: 167–178.

36.

Rodriguez-Rodriguez

Castaneda

Vazquez-Rodriguez

, et al. Influence of CD40 rs1883832 polymorphism in susceptibility to and clinical manifestations of biopsy-proven giant cell arteritis. J Rheumatol 2010; 37: 2076–2080.

37.

Liu

Chao

Wang

Lei

. Expression of CD40 and CD40 ligand among cell populations within rheumatoid synovial compartment. Autoimmunity 2001; 34: 107–113.

38.

Lee

Bae

Choi

Song

. Associations between the functional CD40 rs4810485 G/T polymorphism and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Lupus 2015; 24: 1177–1183.