The X-linked hyper-IgM syndrome - Clinical and immunologic features of 79 patients
The X-linked hyper-IgM syndrome - Clinical and immunologic features of 79 patients
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DOI：
10.1097/01.md.0000100046.06009.b0
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发表时间：
2003-11-01
期刊：
影响因子：
1.6
通讯作者：
Conley, ME
中科院分区：
文献类型：
--
作者：
Winkelstein, JA;Marino, MC;Conley, ME
x连锁高IgM （XHIGM）综合征是一种罕见的原发性免疫缺陷疾病，由CD40配体基因突变引起，其特征是血清IgM正常或升高，IgG和IgA水平降低，t细胞功能缺陷。由于其罕见性，任何研究者或机构都很难对这种疾病进行全面的临床描述。因此，美国建立了一个全国性的登记系统，为相对较多的XHIGM综合征患者提供人口统计学、遗传学、免疫学和临床信息。在1997年1月至2002年7月期间，共有来自60个无血缘关系家庭的79名患者登记。估计最低发病率约为1/ 1030,000活产。所有患者都有明显的IgG缺乏症，大多数有IgA缺乏症，但只有一半的患者有IgM水平升高。大多数患者最初表现为感染易感性增加的病史，包括卡氏肺囊虫肺炎。出生在先前有患病个体的家庭中的患者的平均诊断年龄明显更早。然而，只有三分之一的患者出生在以前有感染个体的家庭中，因为在出现任何临床症状之前存在阳性家族史而被诊断出来。超过一半的患者在1岁时出现免疫缺陷症状并被诊断出来，超过90%的患者在4岁时被诊断出来。最突出的临床感染是肺炎（占81%）。上呼吸道感染（49%），包括鼻窦炎（43%）和复发性中耳炎（43%），复发性/持续性腹泻（34%），中枢神经系统感染（14%），败血症（13%），蜂窝织炎（13%），肝炎（9%）和骨髓炎（1%）。除了被包裹的细菌引起的感染外，机会性感染相对常见，由卡氏假体、疱疹病毒家族成员（包括巨细胞病毒）、隐孢子虫、隐球菌、念珠菌、组织原体和巴尔通体引起。5例患者发生硬化性胆管炎，其中4例伴有隐孢子虫感染。8名病人在登记时已经死亡；肺炎2例（卡氏疟原虫1例、巨细胞病毒1例），脑炎2例（ECHO病毒1例、巨细胞病毒1例），恶性肿瘤2例（均为肝细胞癌），隐孢子虫所致的硬化性胆管炎1例，溶血性尿毒症综合征1例。
The X-linked hyper-IgM (XHIGM) syndrome is an uncommon primary immunodeficiency disease caused by mutations in the gene for CD40 ligand and characterized by normal or elevated serum IgM, reduced levels of IgG and IgA, and defective T-cell function. Because of its rarity, it has been difficult for any single investigator or institution to develop a comprehensive clinical picture of this disorder. Accordingly, a national registry was developed in the United States to provide demographic, genetic, immunologic, and clinical information on a relatively large number of patients with the XHIGM syndrome.A total of 79 patients from 60 unrelated families were registered between January 1997 and July 2002. The estimated minimal incidence was approximately 1/1,030,000 live births. All of the patients had significant IgG deficiency and most had IgA deficiency, but only one-half had elevated IgM levels. Most patients presented initially with a history of an increased susceptibility to infection including Pneumocystis carinii pneumonia. The average age of diagnosis was significantly earlier in patients born into a family with a previously affected individual. However, only one-third of the patients bom into a family with a previously affected individual were diagnosed exclusively because of the presence of the positive family history before any clinical symptoms developed. Over half the patients developed symptoms of immunodeficiency and were diagnosed by 1 year of age, and over 90% by 4 years of age.The most prominent clinical infections were pneumonia (81% of patients). upper respiratory infections (49%) including sinusitis (43%) and recurrent otitis (43%), recurrent/protracted diarrhea (34%), central nervous system infections (14%), sepsis (13%), cellulitis (13%), hepatitis (9%), and osteomyelitis (1%). In addition to infections caused by encapsulated bacteria, opportunistic infections were relatively common and were caused by P. carinii, members of the herpes virus family (including cytomegalovirus), Cryptosporidium, Cryptococcus, Candida, Histoplasma, and Bartonella. Sclerosing cholangitis occurred in 5 patients and in 4 of these was associated with Cryptosporidium infection.Eight patients had died at the time of their entry into the Registry; 2 of pneumonia (1 P. carinii and 1 cytomegalovirus), 2 of encephalitis (1 ECHO virus and 1 cytomegalovirus), 2 of malignancy (both hepatocellular carcinoma), 1 of sclerosing cholangitis caused by Cryptosporidium, and 1 of hemolytic uremic syndrome.