Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
Int J Immunogenet. 2010 Apr;37(2):79-82. doi: 10.1111/j.1744-313X.2009.00893.x. Epub 2010 Jan 14.
Antibodies that block factor VIII (FVIII) activity appear in some haemophilia A patients treated with FVIII replacement therapy and severely impaired treatment. To date, the mechanisms that lead to this immune response are unknown. In this work, haplotypes of cytokine interleukin 10 (IL-10) gene have been associated with the presence of FVIII inhibitors in a group of Brazilian haemophilia A patients. The coexistence of a haplotype defining high IL-10 synthesis and one defining an intermediate production of cytokines is found to be associated with the group of patients who have a history of inhibitor development. Additionally, the coexistence of haplotypes defining high and low IL-10 syntheses is strongly associated with the group of negative inhibitors. These results have shown that the simple association considering only the presence or the absence of a haplotype and the development of inhibitors in haemophilia A is not sufficient. Data obtained in this work sustain the idea that the genetic studies may partly explain why only approximately 25% of haemophilia A patients develop FVIII inhibitors. Other genetic issues and details of the protein replacement therapy should be considered to measure the chances of a patient to develop anti-FVIII antibodies.
抗体可阻断因子 VIII（FVIII）的活性，在接受 FVIII 替代疗法治疗的部分血友病 A 患者中出现，并严重影响治疗效果。迄今为止，导致这种免疫反应的机制尚不清楚。在这项工作中，细胞因子白细胞介素 10（IL-10）基因的单倍型与巴西血友病 A 患者群体中 FVIII 抑制剂的存在相关联。发现一种单倍型定义高 IL-10 合成，另一种单倍型定义细胞因子中间产量的共存与有抑制剂发展史的患者群体相关联。此外，高和低 IL-10 合成定义的单倍型共存与阴性抑制剂群体强烈相关联。这些结果表明，仅考虑单倍型的存在与否以及血友病 A 抑制剂的发展情况的简单关联是不够的。本工作获得的数据支持这样一种观点，即遗传研究可能部分解释了为什么只有约 25%的血友病 A 患者会产生 FVIII 抑制剂。还应考虑其他遗传问题和蛋白质替代疗法的细节，以衡量患者产生抗 FVIII 抗体的可能性。
