Immunological and genetic analysis of 65 patients with a clinical suspicion of X linked hyper-IgM
Immunological and genetic analysis of 65 patients with a clinical suspicion of X linked hyper-IgM
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DOI：
10.1136/mp.56.5.256
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发表时间：
2003-10-01
期刊：
影响因子：
--
通讯作者：
Cale, CM
中科院分区：
文献类型：
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作者：
Gilmour, KC;Walshe, D;Cale, CM
背景：X连锁超IgM（XHIM）是一种原发性免疫缺陷，由肿瘤坏死因子超家族5基因TNFSF5（也称为CD40配体（CD40L）基因）突变引起。患者经常出现反复感染，确诊 XHIM 可以采取适当的治疗干预措施，包括替代免疫球蛋白、抗生素和骨髓移植。目的：审查和优化该机构对 XHIM 的诊断策略。方法：将 65 名男孩的样本转送到该中心，对疑似 XHIM 进行进一步调查。对结果进行了审查，其中包括对选定患者进行流式细胞术全血测定 CD40L 表达，然后进行突变分析。 结果：21 名患者未能表达 CD40L，其中 20 名患者发现了 TNFSF5 突变。相比之下，在CD40L弱表达的16名患者中未发现TNFSF5突变。有趣的是，四分之一患有 TNFSF5 突变的确诊 XHIM 患者的 IgG、IgA 和 IgM 浓度较低。大多数剩余的 XHIM 患者具有正常或升高的 IgM 以及低浓度 IgA 和 IgG 的经典模式。 结论：这项研究证明了全血染色方法作为快速筛查以选择患者进行后续 TNFSF5 突变分析的有用性，并显示了统一的蛋白质/遗传诊断策略的好处。
Background: X linked hyper-IgM (XHIM) is a primary immunodeficiency caused by mutations in the tumour necrosis factor superfamily 5 gene, TNFSF5, also known as the CD40 ligand (CD40L) gene. Patients often present with recurrent infections, and confirmation of a diagnosis of XHIM enables appropriate therapeutic interventions, including replacement immunoglobulin, antibiotics, and bone marrow transplantation.Aim: To review and optimise the institution's diagnostic strategy for XHIM.Method: Samples from 65 boys were referred to this centre for further investigation of suspected XHIM. The results, which included a flow cytometric whole blood assay for CD40L expression followed by mutation analysis in selected patients, were reviewed.Results: Twenty one patients failed to express CD40L and TNFSF5 mutations were found in 20 of these patients. In contrast, no TNFSF5 mutations were found in 16 patients with weak expression of CD40L. Interestingly, one quarter of patients with confirmed XHIM who had TNFSF5 mutations had low concentrations of IgG, IgA, and IgM. Most of the remaining patients with XHIM had the classic pattern of normal or raised IgM with low concentrations of IgA and IgG.Conclusions: This study demonstrates the usefulness of the whole blood staining method as a rapid screen to select patients for subsequent TNFSF5 mutation analysis, and shows the benefits of a unified protein/genetic diagnostic strategy.