Flow Cytometry Service, Clinical Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Blood Transfus. 2023 May;21(3):227-234. doi: 10.2450/2022.0088-22. Epub 2022 Aug 5.
In neonates, antibody-mediated destruction of neutrophils may occur as a consequence of auto- or isoimmune disorders. There are few studies on this topic, and particularly on neonatal alloimmune neutropenia (NAN).
We retrospectively evaluated the clinical and molecular/serological findings of 83 neutropenic infants referred to our Reference Laboratory for diagnostic evaluation of NAN, from 2008 to 2021. We also genotyped 260 Italian healthy subjects for the four principal human neutrophil antigens (HNA).
The diagnosis of NAN was confirmed in 31 cases. The other 52 cases were autoimmune neutropenia (n=21), neutropenia caused by maternal neutrophil autoantibodies (n=8), neutropenia of non-immune origin (n=17), and cases in which a diagnosis could not be reached (n=6). The median age at neutropenia onset and absolute neutrophil count (ANC) were significantly lower in NAN than in non-NAN cases (1 vs 30 days, p<0.005; 330 vs 580/μL, p=0.003, respectively). About 74% of NAN cases developed neutropenia within the first week of life and laboratory investigations were required within 2 weeks. In five patients the neutropenia was discovered at the end of the first month of life and they were referred to our laboratory 1-2 months later when neutropenia had already resolved. Infections were seen in 19% of NAN cases. The median time to resolution of NAN was 31 days. About 50% of NAN cases were due to alloantibodies against HNA-1b, the most frequent allele of HNA-1 in the Italian population (allele frequency 0.63). In five cases of NAN the mothers had an HNA-1 null phenotype, a frequency higher than that observed in our Italian cohort.
NAN should be considered by clinicians in infants with neutropenia onset within 5-7 days of life, even though there can be other reasons for a low ANC. If neutropenia is detected later, benign neutropenia seems more likely, although persistence of maternal alloantibodies cannot be ruled out.
在新生儿中，抗体介导的中性粒细胞破坏可能是自身免疫或同种免疫紊乱的结果。关于这个主题的研究很少，特别是关于新生儿同种免疫性中性粒细胞减少症（NAN）。
我们回顾性评估了 2008 年至 2021 年期间，83 名中性粒细胞减少症婴儿因诊断 NAN 而被转诊至我们的参考实验室的临床和分子/血清学发现。我们还对 260 名意大利健康受试者进行了四个主要人类中性粒细胞抗原（HNA）的基因分型。
在 31 例中，NAN 的诊断得到确认。其余 52 例为自身免疫性中性粒细胞减少症（n=21）、母体中性粒细胞自身抗体引起的中性粒细胞减少症（n=8）、非免疫来源的中性粒细胞减少症（n=17）和无法明确诊断的病例（n=6）。NAN 组的中性粒细胞减少症发病年龄和绝对中性粒细胞计数（ANC）中位数明显低于非-NAN 组（1 与 30 天，p<0.005；330 与 580/μL，p=0.003）。大约 74%的 NAN 病例在生命的第一周内发生中性粒细胞减少症，需要在 2 周内进行实验室检查。在 5 名患者中，中性粒细胞减少症在生命的第一个月结束时被发现，当中性粒细胞减少症已经缓解时，他们在 1-2 个月后被转介到我们的实验室。NAN 病例中有 19%发生感染。NAN 的中位缓解时间为 31 天。大约 50%的 NAN 病例是由于针对 HNA-1b 的同种抗体引起的，HNA-1b 是意大利人群中 HNA-1 的最常见等位基因（等位基因频率 0.63）。在 5 例 NAN 中，母亲具有 HNA-1 无效表型，其频率高于我们意大利队列中的观察值。
对于出生后 5-7 天内中性粒细胞减少症发病的婴儿，临床医生应考虑 NAN，尽管 ANC 降低可能还有其他原因。如果中性粒细胞减少症较晚发现，良性中性粒细胞减少症似乎更有可能，但不能排除母体同种抗体的持续存在。
