Laboratory of Research in Immunology of Renal Transplantation and Immunopathology (LR03SP01) Charles Nicolle Hospital, Tunis El Manar University, Bd 9 Avril, 1006 Bab Saadoun, Tunis, Tunisia.
Biomark Res. 2013 May 16;1(1):20. doi: 10.1186/2050-7771-1-20.
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).
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.
CD14T 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 CD14T 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 CD14T/T genotype (92%) comparatively to those with C/C and C/T genotypes (72.5%), p = 0.04. Moreover, SLE patients carrying CD14T/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.
The CD14 (-159)*T allele seems to be associated with susceptibility to SLE and arthritis occurrence.
Toll 样受体 4（TLR4）及其共受体 CD14 通过识别 PAMP 并信号转导适应性反应，在固有免疫中发挥重要作用。这些受体可以识别主要是自身抗原的内源性配体。此外，TLR4（Asp299Gly）和 CD14（C/T-159）多态性（SNP）可能会定性和/或定量地改变其表达。因此，它们可能与自身免疫性疾病有关，并可能影响系统性红斑狼疮（SLE）和类风湿关节炎（RA）的易感性和严重程度。
采用聚合酶链反应（PCR）-RFLP 方法对 127 例 SLE 患者、100 例 RA 患者和 114 名年龄和性别匹配的健康对照者的 TLR4（Asp299Gly）和 CD14（C/T-159）SNP 进行基因分型。
与对照组（0.355）相比，SLE 患者的 CD14T 等位基因（0.456）明显更为频繁，p=0.02，比值比（95%可信区间）=1.53[1.04-2.24]。RA 患者中，CD14T 等位基因（0.405）的高频率无统计学意义，p=0.28。TLR4（Asp299Gly）SNP 的研究也与 SLE 或 RA 无关。根据临床和生物学特征分析这些 SNP 显示，携带 CD14T/T 基因型的 SLE 患者关节炎的频率明显更高（92%），而携带 C/C 和 C/T 基因型的患者关节炎的频率明显更高（72.5%），p=0.04。此外，携带 CD14T/T/TLR4*A/A 单倍型的 SLE 患者关节炎的发生率明显高于 SLE 组的其余患者（91.3%）（73%），p=0.044，且经年龄和性别调整后的多变量分析也证实了这一点，p=0.01。
CD14（-159）*T 等位基因似乎与 SLE 和关节炎发生的易感性有关。
