Prevalence and epitope specificity of non-neutralising antibodies in a large cohort of haemophilia A patients without inhibitors
Prevalence and epitope specificity of non-neutralising antibodies in a large cohort of haemophilia A patients without inhibitors
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DOI：
10.1160/th10-10-0668
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发表时间：
2011-06-01
影响因子：
6.7
通讯作者：
Lavigne-Lissalde, Geraldine
中科院分区：
文献类型：
--
作者：
Lebreton, Aurelien;Lapalud, Priscilla;Lavigne-Lissalde, Geraldine
Antibodies (inhibitors and non-neutralising antibodies [NNA]) directed against factor VIII (FVIII) remain the main iatrogenic complication in haemophilia A (HA) patients. Inhibitors reduce FVIII pro-coagulant properties, whereas NNA are directed against non-functional epitopes. NNA are poorly studied and their prevalence, epitope specificity and physiopathology inadequately defined. The aim of this study was first to evaluate NNA prevalence in a French retrospective multicentric series of 210 patients without inhibitors, then to determine their epitope specificity (against the heavy chain [HC] or the light chain [LC] of FVIII) and particularly to assess the prevalence of anti-B domain NNA using specifically designed x-MAP assays. NNA occurred in 18.1% of patients (38/210) and their prevalence was not influenced by the severity of the disease. Among the 38 patients with NNA, 73.7% had anti-FVIII Abs against the HC, 13.2% against the LC and 13.2% had anti-FVIII Abs against both chains. There is thus a clear immuno-dominance of the HC of FVIII in the epitope profile of NNA, whatever the severity of HA. The proportion of NNA that recognised the B domain was 18.4% (n=7/38). A multivariate analysis did not highlight differences in NNA occurrence between patients treated with recombinant FVIII or with plasma-derived FVIII (19.6% vs. 14.9%, p=0.53).
