北欧中度 A 型和 B 型血友病患者体内的非中和抗体（MoHem 研究）

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis Pub Date : 2024-11-01 DOI:10.1016/j.rpth.2024.102611

Ragnhild J. Måseide MD, PhD , Erik Berntorp MD, PhD , Jan Astermark MD, PhD , Anna Olsson MD, PhD , Maria Bruzelius MD, PhD , Tony Frisk MD, PhD , Vuokko Nummi MD, PhD , Riitta Lassila MD, PhD , Karin Strandberg MD, PhD , Geir E. Tjønnfjord MD, PhD , Pål A. Holme MD, PhD

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引用次数: 0

摘要

背景非中性抗体（NNAs）对中度血友病的影响尚不明确。目的探讨北欧中度血友病 A（MHA）和 B（MHB）患者体内 NNAs 的存在与治疗方式、临床结果、抑制剂史以及相应的因子 VIII (FVIII)/ 因子 IX (FIX) 基因突变的关系。结果分析了 137 名 MoHem 研究参与者（中位年龄 29 岁；Q1-Q3，15-54 岁）的血浆样本。无论是否进行预防性治疗或按需治疗，82 名 MHA 患者中有 11 人（13%）和 55 名 MHB 患者中有 7 人（13%）存在 NNA，最常出现在暴露 150 天 (ED) 之后。三名 NNA 阳性患者曾出现高滴度抑制剂，但目前的分析结果为阴性（0.6 BU/mL）。NNA 阳性和阴性患者的基线 FVIII/FIX 活性相似。目前的出血率较低，但 NNA 患者的血友病关节健康评分较高（7 [中位数]；Q1-Q3，3-20 vs. 4；1-9）（P = .02），且更常接受关节成形术或关节固定术（5 [33%] vs. 15 [13%]）（P = .03）。与无 NNA 的患者相比，有 NNA 的患者血友病关节病更为严重。NNAs与血友病临床结果之间的关系应在大型队列中进一步探讨，包括药代动力学和重复采血的纵向观察。

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Nonneutralizing antibodies in Nordic persons with moderate hemophilia A and B (the MoHem study)

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Nonneutralizing antibodies in Nordic persons with moderate hemophilia A and B (the MoHem study)

Background

The impact of nonneutralizing antibodies (NNAs) in moderate hemophilia is elusive.

Objectives

To explore the presence of NNAs in Nordic persons with moderate hemophilia A (MHA) and B (MHB) in relation to treatment modality, clinical outcome, history of inhibitor, and the corresponding factor VIII (FVIII)/factor IX (FIX) gene mutation.

Methods

A cross-sectional multicenter study covering persons with MHA and MHB in Sweden, Finland, and Norway. Inhibitors were analyzed with the Bethesda assay, and NNAs were detected by enzyme-linked immunosorbent assay.

Results

Plasma samples from 137 MoHem study participants (median age 29 years; Q1-Q3, 15-54) were analyzed. NNAs were present in 11 of 82 (13%) of people with MHA and 7 of 55 (13%) of those with MHB irrespective of prophylactic or on-demand treatment, most frequently after 150 exposure days (EDs). Three NNA positive patients had a history of high-titer inhibitor, but current analyses were negative (<0.6 BU/mL). Baseline FVIII/FIX activity was similar among NNA positive and negative patients. Current bleeding rates were low, but patients with NNAs captured a higher Hemophilia Joint Health Score (7 [median]; Q1-Q3, 3-20 vs. 4; 1-9) (P = .02) and had more frequently undergone arthroplasty or arthrodesis (5 [33%] vs. 15 [13%]) (P = .03).

Conclusion

NNAs were detected in 13% of Nordic persons with MHA and MHB, most frequently after 150 EDs. Patients with NNAs had more severe hemophilic arthropathy than patients without NNAs. The relationship between NNAs and clinical outcome in hemophilia should be further explored in a large cohort including pharmacokinetics and longitudinal observations with repeated blood sampling.

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