Polymorphisms of Toll-like receptor-4 and CD14 in systemic lupus erythematosus and rheumatoid arthritis

被引：22

作者：

Dhaouadi T. ^{[1
]}

Sfar I. ^{[1
]}

Haouami Y. ^{[1
]}

Abdelmoula L. ^{[2
]}

Turki S. ^{[3
]}

Hassine L.B. ^{[4
]}

Zouari R. ^{[2
]}

Khedher A. ^{[3
]}

Khalfallah N. ^{[4
]}

Abdallah T.B. ^{[1
]}

Gorgi Y. ^{[1
]}

机构：

[1] Laboratory of Research in Immunology of Renal Transplantation and Immunopathology (LR03SP01), Charles Nicolle Hospital, Tunis El Manar University, 1006 Bab Saadoun, Tunis

[2] Rheumatology Department Charles Nicolle Hospital, Tunis El Manar University, Tunis

[3] Internal Medicine Department A Charles Nicolle Hospital, Tunis El Manar University, Tunis

[4] Internal Medicine Department B Charles Nicolle Hospital, Tunis El Manar University, Tunis

来源：

Biomarker Research | / 1卷 / 1期

关键词：

CD14; Polymorphisms; Rheumatoid arthritis; Systemic lupus erythematosus; TLR4;

D O I：

10.1186/2050-7771-1-20

中图分类号：

学科分类号：

摘要：

Background: Toll-like receptor 4 (TLR4) and its co-receptor CD14 play a major role in innate immunity by recognizing PAMPs and signal the activation of adaptive responses. These receptors can recognize endogenous ligands mainly auto-antigens. In addition, TLR4 (Asp299Gly) and CD14 (C/T -159) polymorphisms (SNPs) may modify qualitatively and/or quantitatively their expression. Therefore, they could be implied in autoimmune diseases and can influence both susceptibility and severity of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).Patients and methods: TLR4 (Asp299Gly) and CD14 (C/T -159) SNPs were genotyped using polymerase chain reaction (PCR)-RFLP in 127 SLE patients, 100 RA patients, and 114 healthy controls matched in age and gender. Results: CD14* allele was significantly more frequent in SLE patients (0.456) comparatively to controls (0.355), p = 0.02 OR (95% CI) = 1.53 [1.04-2.24]. In RA patients, the higher frequency of CD14*;T allele (0.405) failed to reach significance, p = 0.28. Investigation of the TLR4 (Asp299Gly) SNP showed no significant association neither with SLE nor with RA.Analysis of these SNPs according to clinical and biological features showed a significant higher frequency of arthritis in SLE patients carrying CD14*/T genotype (92%) comparatively to those with C/C and C/T genotypes (72.5%), p = 0.04. Moreover, SLE patients carrying CD14*/T/TLR4*A/A haplotype had significantly more arthritis (91.3%) than the rest of SLE group (73%), p = 0,044 and confirmed by multivariable analysis after adjustment according to age and gender, p = 0.01. Conclusion: The CD14 (-159)* allele seems to be associated with susceptibility to SLE and arthritis occurrence. © 2013 Dhaouadi et al.; licensee BioMed Central Ltd.

引用

共 30 条

[1]

Kaplan M.J., Apoptosis in systemic lupus erythematosus, Clin Immunol, 112, pp. 210-218, (2004)

[2]

Schedel J., Gay R.E., Kuenzler P., Seemayer C., Simmen B., Michel B.A., Gay S., FLICE-inhibitory protein expression in synovial fibroblasts and at sites of cartilage and bone erosion in rheumatoid arthritis, Arthritis Rheum, 46, pp. 1512-1518, (2002)

[3]

Liu H., Pope R.M., The role of apoptosis in rheumatoid arthritis, Curr Opin Pharmacol, 3, pp. 317-322, (2003)

[4]

Richez C., Blanco P., Rifkin I., Moreau J.F., Schaeverbeke T., Role for toll-like receptors in autoimmune disease: The example of systemic lupus erythematosus, Joint Bone Spine, 78, pp. 124-130, (2011)

[5]

Okayama N., Fujimura K., Suehiro Y., Hamanaka Y., Fujiwara M., Matsubara T., Maekawa T., Hazama S., Oka M., Nohara H., Kayano K., Okita K., Hinoda Y., Simple genotype analysis of the Asp299Gly polymorphism of the Toll-like receptor-4 gene that is associated with lipopolysaccharide hyporesponsiveness, J Clin Lab Anal, 16, 1, pp. 56-58, (2002)

[6]

Schmitt C., Humeny A., Becker C.M., Brune K., Pahl A., Polymorphisms of TLR4: rapid genotyping and reduced response to lipopolysaccharide of TLR4 mutant alleles, Clin Chem, 48, 10, pp. 1661-1667, (2002)

[7]

LeVan T.D., Bloom J.W., Bailey T.J., Karp C.L., Halonen M., Martinez F.D., Vercelli D., A common single nucleotide polymorphism in the CD14 promoter decreases the affinity of Sp protein binding and enhances transcriptional activity, J Immunol, 167, pp. 5838-5844, (2012)

[8]

Hochberg M.C., Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus, Arthritis Rheum, 40, 9, (1997)

[9]

Arnett F.C., Edworthy S.M., Bloch D.A., Mcshane D.J., Fries J.F., Cooper N.S., Healey L.A., Kaplan S.R., Liang M.H., Luthra H.S., Medsger T.A., Mitchell D.M., Neustadt D.H., Pinals R.S., Schaller J.G., Sharp J.T., Wilder R.L., Hunder G.G., The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis, Arthritis Rheum, 31, pp. 315-324, (1988)

[10]

Miller S.A., Dykes D.D., Polesky H.G., A sampling salting out procedure for extracting DNA from human nucleated cells, Nucleic Acids Res, 16, (1988)

← 1 2 3 →