Alloantibodies to factor VIII in haemophilia
Alloantibodies to factor VIII in haemophilia
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DOI：
10.1111/j.1365-2516.2010.02468.x
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发表时间：
2011-07-01
期刊：
影响因子：
3.9
通讯作者：
Green, D.
中科院分区：
文献类型：
--
作者：
Zakarija, A.;Harris, S.;Green, D.
多达三分之一的血友病A患者会产生因子VIII（FVIII）同种抗体（抑制剂）。Bethesda检测法可检测抑制剂，但相对不敏感。最近，一种新的基于荧光的免疫分析（FLI）被开发用于抗体检测。本研究的目的是评估通过FLI测量的抑制物的患病率。在成人血友病A患者中进行了FVIII、FVIII抑制剂测定（采用Nijmegen改良的Bethesda测定法）和FVIII抑制剂测定（采用FLI）。46名患者（中位年龄39岁）的数据完整，其中72%为重度，7%为中度，22%为轻度。Bethesda检测仅在2例患者（4%）中呈阳性，而FLI在46例患者中的23例（50%）中呈阳性，数值范围为0.4至33.7 nm（中位数为3.5 nm）。在19.5%的患者中，FLI滴度超过7.0 nm，除1例患者外，所有患者均患有重度血友病。FLI抗体阳性患者不太可能是HIV阳性（30% vs. 70%，P = 0.02）。使用预防性治疗方案与较低的抗体发生率相关; 23例可检测到抗体的患者中只有2例接受预防性治疗，抗体> 7 nm的患者中无1例接受预防性治疗，而23例无抗体的患者中有9例接受预防性治疗（P = 0.03）。使用重组与血浆衍生因子的患者中抑制物的存在没有差异。FLI检测到的抗体在血友病A患者中很常见，但在HIV阳性或接受定期FVIII预防的患者中不太常见。
Up to one-third of haemophilia A patients develop factor VIII (FVIII) alloantibodies (inhibitors). The Bethesda assay detects inhibitors but is relatively insensitive. Recently, a new fluorescence-based immunoassay (FLI) was developed for antibody detection. The aim of this study was to assess the prevalence of inhibitors as measured by FLI. Assays of FVIII, FVIII inhibitor by Bethesda assay with Nijmegen modification, and FVIII inhibitor by FLI were performed on adult patients with haemophilia A. Data were complete for 46 patients (median age 39), of whom 72% were severe, 7% moderate and 22% mild. The Bethesda assay was positive in only two patients (4%), while FLI was positive in 23 of 46 patients (50%), with values ranging from 0.4 to 33.7 nm (median 3.5 nm). FLI titres exceeded 7.0 nm in 19.5% of patients, all but one of whom had severe haemophilia. FLI antibody-positive patients were less likely to be HIV positive (30% vs. 70%, P = 0.02). The use of a prophylaxis regimen was associated with a lower incidence of antibody; only two of 23 patients with detectable antibody and none of those with antibody > 7 nm were on a prophylaxis regimen, while nine of 23 patients without antibody were on prophylaxis, (P = 0.03). There was no difference in inhibitor presence in patients using recombinant versus plasma-derived factor. Antibodies detected by FLI are frequent in patients with haemophilia A, but are less common in those who are HIV positive or are receiving regular FVIII prophylaxis.