Disciplina de Hematologia e Hemoterapia, Escola Paulista de Medicina - Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brasil.
Int J Lab Hematol. 2012 Aug;34(4):356-61. doi: 10.1111/j.1751-553X.2012.01400.x. Epub 2012 Jan 27.
Autoimmune haemolytic anaemia (AIHA) is defined as the increased destruction of red blood cells (RBCs) in the presence of anti-RBC autoantibodies and/or complement. Its pathogenesis is multifactorial and includes changes in mechanisms of cytokine production and functionality. A number of recent studies have implicated cytokines polymorphisms in the pathogenesis of autoimmune diseases. The aim of this study was to determine the frequency of polymorphisms of tumour necrosis factor alpha (TNF-α), lymphotoxin-α (LT-α), interleukin 10 (IL-10), interleukin 12 (IL-12) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in patients with AIHA in comparison with healthy individuals.
The study population consisted of 17 patients with AIHA and 40 healthy controls. The polymorphisms for TNF-α-308, LT-α +252, IL-10 -592, IL-12 +1188 and CTLA-4 +49 were examined by polymerase chain reaction followed by specific restriction enzyme digestion.
There was no significant difference in the phenotypic distributions of polymorphisms of the TNF-α, IL-10, IL-12 and CTLA-4 between the patients and controls. Compared with healthy controls, patients with AIHA had a significant higher frequency of LT-α (+252) AG phenotype (41%vs. 13%; P = 0.032).
In this study, no significant differences on the frequency of TNF-α, IL-10, IL-12 and CTLA-4 polymorphisms between patients with AIHA and controls was found, suggesting that the targeted polymorphisms do not influence on the emergence and evolution of the disease. However, the LT-α +252 polymorphism might have an effect for AIHAI development, suggesting that further studies are necessary to clear up this question.
自身免疫性溶血性贫血(AIHA)定义为在存在抗 RBC 自身抗体和/或补体的情况下红细胞(RBC)的破坏增加。其发病机制是多因素的,包括细胞因子产生和功能变化的机制。一些最近的研究表明细胞因子多态性与自身免疫性疾病的发病机制有关。本研究旨在确定自身免疫性溶血性贫血患者中肿瘤坏死因子-α(TNF-α)、淋巴毒素-α(LT-α)、白细胞介素 10(IL-10)、白细胞介素 12(IL-12)和细胞毒性 T 淋巴细胞抗原-4(CTLA-4)的多态性频率与健康个体相比。
研究人群包括 17 例 AIHA 患者和 40 名健康对照者。采用聚合酶链反应(PCR)结合特异性限制性内切酶消化法检测 TNF-α-308、LT-α+252、IL-10-592、IL-12+1188 和 CTLA-4+49 多态性。
患者和对照组 TNF-α、IL-10、IL-12 和 CTLA-4 多态性的表型分布无显著差异。与健康对照组相比,AIHA 患者 LT-α(+252)AG 表型的频率显著升高(41%对 13%;P = 0.032)。
本研究未发现 AIHA 患者与对照组 TNF-α、IL-10、IL-12 和 CTLA-4 多态性频率存在显著差异,提示靶向多态性对疾病的发生和发展无影响。然而,LT-α+252 多态性可能对 AIHAI 的发展有影响,提示需要进一步研究来澄清这一问题。