First Report of the Hyper-IgM Syndrome Registry of the Latin American Society for Immunodeficiencies: Novel Mutations, Unique Infections, and Outcomes
First Report of the Hyper-IgM Syndrome Registry of the Latin American Society for Immunodeficiencies: Novel Mutations, Unique Infections, and Outcomes
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DOI：
10.1007/s10875-013-9980-4
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发表时间：
2014-02-01
影响因子：
9.1
通讯作者：
Condino-Neto, Antonio
中科院分区：
文献类型：
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作者：
Cabral-Marques, Otavio;Klaver, Stefanie;Condino-Neto, Antonio
高IgM（HIGH M）综合征是一组异质性疾病，其特征在于与IgG、伊加和IgE缺失或降低相关的血清IgM水平正常或升高。在这里，我们总结了来自拉丁美洲免疫缺陷学会（LASID）的HIGM综合征登记处的数据。在来自51个家族的58名患者中，迄今为止在登记处报告了具有HIGH M综合征临床表型的37名患者中鉴定出分子缺陷。我们回顾性分析了这37例患者的临床、免疫学和分子生物学资料。25个家系中35例患者存在CD40配体（CD40L）缺陷，2例无血缘关系患者存在活化诱导的胞苷脱氨酶（AID）缺陷。在CD40L基因（CD40LG）中发现了5个以前未报道的突变。呼吸道感染，主要是肺炎，是最常见的临床表现。以前未描述的真菌和机会性感染观察到CD40 L缺陷的患者，但没有在两个AID缺陷的患者。这些包括由肺炎支原体、粘质沙雷氏菌或曲霉菌引起的肺炎和由微孢子虫或贝氏等孢子虫引起的腹泻的首批病例。除了4例CD40L缺陷患者死于推定的中枢神经系统感染或脓毒症的并发症外，本研究中报告的所有患者均存活。4例CD40L缺陷患者成功进行了骨髓移植。本报告描述了拉丁美洲HIGM综合征的临床和遗传谱，并扩展了对热带地区这种综合征的基因型和表型的理解。
Hyper-IgM (HIGM) syndrome is a heterogeneous group of disorders characterized by normal or elevated serum IgM levels associated with absent or decreased IgG, IgA and IgE. Here we summarize data from the HIGM syndrome Registry of the Latin American Society for Immunodeficiencies (LASID). Of the 58 patients from 51 families reported to the registry with the clinical phenotype of HIGM syndrome, molecular defects were identified in 37 patients thus far. We retrospectively analyzed the clinical, immunological and molecular data from these 37 patients. CD40 ligand (CD40L) deficiency was found in 35 patients from 25 families and activation-induced cytidine deaminase (AID) deficiency in 2 unrelated patients. Five previously unreported mutations were identified in the CD40L gene (CD40LG). Respiratory tract infections, mainly pneumonia, were the most frequent clinical manifestation. Previously undescribed fungal and opportunistic infections were observed in CD40L-deficient patients but not in the two patients with AID deficiency. These include the first cases of pneumonia caused by Mycoplasma pneumoniae, Serratia marcescens or Aspergillus sp. and diarrhea caused by Microsporidium sp. or Isospora belli. Except for four CD40L-deficient patients who died from complications of presumptive central nervous system infections or sepsis, all patients reported in this study are alive. Four CD40L-deficient patients underwent successful bone marrow transplantation. This report characterizes the clinical and genetic spectrum of HIGM syndrome in Latin America and expands the understanding of the genotype and phenotype of this syndrome in tropical areas.