Prevalence and clinical significance of low-avidity HPA-1a antibodies in women exposed to HPA-1a during pregnancy.
Prevalence and clinical significance of low-avidity HPA-1a antibodies in women exposed to HPA-1a during pregnancy.
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DOI：
10.1111/j.1537-2995.2012.03903.x
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发表时间：
2013-06
期刊：
影响因子：
2.9
通讯作者：
Aster RH
中科院分区：
文献类型：
--
作者：
Peterson JA;Kanack A;Nayak D;Bougie DW;McFarland JG;Curtis BR;Aster RH
最近的研究表明，传统方法无法检测到的 HPA-1a 特异性、低亲和力母体抗体可能会导致新生儿同种免疫性血小板减少症 (NAIT)。我们进行了研究以进一步确定此类抗体的发生率和临床意义。表面等离子共振分析用于检测疑似 NAIT 病例的 HPA-1a 阴性、“抗体阴性”母亲中的低亲和力抗体。在新开发的 NOD/SCID 小鼠模型中检查了检测到的抗体促进人血小板 (PLT) 免疫破坏的能力。在 3478 例 NAIT 疑似病例中，发现了 677 名 HPA-1a 阴性母亲。通过常规抗体检测在 616 例 (91%) 病例中检测到 HPA-1a 特异性抗体。其余 61 例中有 18 例 (9%) 鉴定出低亲和力 HPA-1a 特异性抗体。对 13 例病例的临床随访显示，其中 8 例是因为疑似 NAIT 而转诊，5 例是因为母亲的姐姐之前生过患有 NAIT 的婴儿。 13 名致敏母亲所生的婴儿中，只有 6 名婴儿在出生时出现有临床意义的血小板减少症。在小鼠中测试的四种低亲和力抗体中的三种可加速 HPA-1a/a 的清除，但不会加速 HPA-1b/b PLT 的清除。 12 名具有低亲和力 HPA-1a 抗体的母亲中，只有 3 名 HLA-DRB3*0101 呈阳性。研究结果证实了之前的报道，即低亲和力 HPA-1a 抗体可引起 NAIT，但表明这种抗体的存在并不能预测婴儿会受到影响。该队列中 HLA-DRB3*0101 的发生率较低 (p < 0.0001)，表明 DRB3*0101 阴性的女性可能倾向于产生低亲和力的 HPA-1a 抗体。
Recent studies suggest that HPA-1a–specific, low-avidity maternal antibodies not detectable by conventional methods can cause neonatal alloimmune thrombocytopenia (NAIT). We performed studies to further define the incidence and clinical significance of this type of antibody. Surface plasmon resonance analysis was used to detect low-avidity antibodies in HPA-1a–negative, “antibody-negative” mothers of suspected NAIT cases. The ability of antibodies detected to promote immune destruction of human platelets (PLTs) was examined in a newly developed NOD/SCID mouse model. Among 3478 suspected cases of NAIT, 677 HPA-1a–negative mothers were identified. HPA-1a–specific antibodies were detected by conventional antibody testing in 616 cases (91%). Low-avidity HPA-1a–specific antibodies were identified in 18 of the remaining 61 cases (9%). Clinical follow-up on 13 cases showed that eight were referred because of suspected NAIT and five because the mother’s sister had previously had an infant with NAIT. Only six infants born to the 13 sensitized mothers had clinically significant thrombocytopenia at birth. Three of four low-avidity antibodies tested in the mouse caused accelerated clearance of HPA-1a/a but not HPA-1b/b PLTs. Only 3 of 12 mothers with low-avidity HPA-1a antibodies were positive for HLA-DRB3*0101. The findings confirm previous reports that low-avidity HPA-1a antibodies can cause NAIT but show that the presence of such an antibody does not predict that an infant will be affected. The low incidence of HLA-DRB3*0101 in this cohort (p < 0.0001) suggests that women negative for DRB3*0101 may be predisposed to produce low-avidity HPA-1a antibodies.
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影响因子：
20.3
作者：
Bougie, Daniel W.;Nayak, Dhirendra;Aster, Richard H.
通讯作者：
Aster, Richard H.
影响因子：
2.9
作者：
Kroll, Hartmut;Feldmann, Korinna;Santoso, Sentot
通讯作者：
Santoso, Sentot
影响因子：
2
作者：
Mao, CY;Guo, JW;Chituwo, BM
通讯作者：
Chituwo, BM
影响因子：
2.7
作者：
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通讯作者：
MULLER, JY
影响因子：
1.5
作者：
KEKOMAKI, R;RAIVIO, P;KERO, P
通讯作者：
KERO, P