Chronic inflammation with sustained unregulated immune stimulation in autoimmune rheumatic diseases (ARD) may be a risk factor for developing lymphoproliferative disorders (LPD). Markers of ARD activity as high erythrocyte sedimentation rate or erosive joint diseases and the development of B-symptoms were accounted as risk factors for LPD development. We investigated the association of five inflammatory cytokine genes single nucleotide polymorphisms (SNPs): TNF-α -308G>A; TGF-β1 gene codon 10 T>C and 25 G>C; IL-10 promoter SNPs -1082 A>G, -819T>C, and -592A>C; IL-6 -174G>C; and IFN-γ 874 T>A with the risk of LPD development in ARD patients. The study was conducted on 70 patients divided into group I, 25 ARD patients diagnosed as RA (n = 15) and SLE (n = 10) and with no history of malignancy; group II, 25 patients diagnosed with LPD and had no ARD; and group III, 20 patients diagnosed with both diseases: ARD and LPD. Cytokine genotyping was analyzed by PCR-sequence-specific primer (PCR-SSP). ARD+LPD patients had significantly higher frequency of TNF-α -308A allele and AA+AG genotype (high TNF-α producers) and IL-10 -1082A allele and AA genotype (low IL-10 producers) than ARD patients (p = 0.003, p = 0.024, p = 0.003, p = 0.03, respectively) with a significantly increased risk of LPD development in ARD patients expressing the corresponding alleles and genotypes. No significant differences were detected in the distribution frequency of either TGF-β1, IL-6, or IFN-γ SNPs between groups I and III or any of the studied SNPs between groups II and III. The distribution frequency of IL-10 ATA haplotype was significantly increased in group III as compared to group I (p = 0.037). The significantly increased frequency of the high-TNF-α- and low-IL-10-producing alleles and genotypes in ARD patients may participate in the provision of a proinflammatory milieu that eventually increases the risk of LPD development.

中文翻译：

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TNF-α -308 G>A 和 IL10 -1082A>G 多态性作为自身免疫性风湿病淋巴组织增生性疾病的潜在危险因素

自身免疫性风湿病 (ARD) 中持续不受调节的免疫刺激的慢性炎症可能是发生淋巴组织增生性疾病 (LPD) 的危险因素。ARD 活动的标志物如高红细胞沉降率或侵蚀性关节疾病和 B 症状的发展被认为是 LPD 发展的危险因素。我们研究了五种炎性细胞因子基因单核苷酸多态性 (SNP) 的关联：TNF-α -308G>A；TGF-β1 基因密码子 10 T>C 和 25 G>C；IL-10 启动子 SNP -1082 A>G、-819T>C 和 -592A>C；IL-6 -174G>C；和 IFN-γ 874 T>A 与 ARD 患者发生 LPD 的风险。该研究对分为 I ​​组的 70 名患者进行，其中 25 名诊断为 RA（n = 15）和 SLE（n = 10）且没有恶性肿瘤病史的 ARD 患者；第二组，25 名诊断为 LPD 且没有 ARD 的患者；和第三组，20 名被诊断患有两种疾病的患者：ARD 和 LPD。细胞因子基因分型通过 PCR 序列特异性引物 (PCR-SSP) 进行分析。ARD+LPD 患者的 TNF-α -308A 等位基因和 AA+AG 基因型（高 TNF-α 生产者）和 IL-10 -1082A 等位基因和 AA 基因型（低 IL-10 生产者）的频率显着高于 ARD 患者（p = 0.003、p = 0.024、p = 0.003、p = 0.03），同时表达相应等位基因和基因型的 ARD 患者发生 LPD 的风险显着增加。在 I 组和 III 组之间的 TGF-β1、IL-6 或 IFN-γ SNP 的分布频率或 II 组和 III 组之间的任何研究的 SNP 的分布频率中没有检测到显着差异。与组 I 相比，组 III 中 IL-10 ATA 单倍型的分布频率显着增加（p = 0.037）。ARD 患者中产生高 TNF-α 和低 IL-10 的等位基因和基因型的频率显着增加，可能参与提供促炎环境，最终增加 LPD 发展的风险。