Prevalence of FVIII inhibitors in severe haemophilia A patients: Effect of treatment and genetic factors in an Indian population
Prevalence of FVIII inhibitors in severe haemophilia A patients: Effect of treatment and genetic factors in an Indian population
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DOI：
10.1111/hae.13633
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发表时间：
2019-01-01
期刊：
影响因子：
3.9
通讯作者：
Mathews, Vikram
中科院分区：
文献类型：
--
作者：
David, Sachin;Nair, Sukesh C.;Mathews, Vikram
前言因子替代疗法治疗血友病A的复杂之处在于产生中和抗体，称为抑制物。抑制剂的形成是多因素的，既有遗传因素，也有环境因素。目的记录重度血友病患者中抑制剂的流行情况，并评估其可能的影响因素。方法在全国各地开展社区夏令营。通过结构化问卷对患者进行评估，并获取血液样本以进行抑制物实验室评估和确定免疫学参数。结果447例受评患者中有87例(19.5%)存在抑制剂。在31例(35.6%)患者中发现了高滴度抑制物(>；5 Bethesda Units[BU])。HLADRB1-13阳性的患者(RR=2.04；95%CI1.06~3.911；P=0.033)，抑制物形成的风险增加，并保留在高滴度亚群。杂合的IL 4-590C/T等位基因降低了抑制物形成的风险(RR=0.22；95%CI 0.108~0.442：P=0.000)。在这项研究中，任何被评估的环境因素与抑制剂的开发都没有显著的相关性。结论严重血友病A患者中抑制剂的总体患病率与常规替代治疗患者中报道的相似。这项研究的数据受其回溯性和横断面研究设计的限制，表明遗传而不是环境更有可能影响抑制剂的发展。
Introduction Factor replacement therapy in treatment of haemophilia A is complicated by the production of neutralising antibodies known as inhibitors. The formation of inhibitors is multifactorial being associated with both genetic and environmental factors. Aim To document the prevalence of inhibitors in severe haemophilia in the community where most patients receive only infrequent episodic replacement therapy and evaluate the factors which could be contributing to it. Methods Community based camps were conducted in different parts of the country. Patients were assessed through a structured questionnaire and blood samples were obtained for laboratory evaluation of inhibitors and defined immunological parameters. Results Inhibitors were present in 87/447 (19.5%) of the evaluated patients. High-titre inhibitor (>5 Bethesda Units [BU]) was identified in 31 (35.6%) patients. HLA DRB1-13-positive cases (RR = 2.04; 95% CI 1.06-3.911; P = 0.033) had an increased risk of inhibitor formation which was retained in the high-titre subset. A decreased risk of inhibitor formation was noted with heterozygous IL4-590 C/T allele (RR = 0.22; 95% CI 0.108-0.442: P = 0.000). There were no significant correlations between any of the evaluated environmental factors and the development of inhibitors in this study. Conclusion The overall prevalence of inhibitors in patients with severe haemophilia A is similar to that reported among patients receiving regular replacement therapy. The data from this study, limited by its retrospective and cross-sectional study design, would suggest that genetic rather than environmental are more likely to impact the development of inhibitors.