Division of Pediatric Immunology, Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey.
Pediatr Allergy Immunol. 2009 Nov;20(7):693-8. doi: 10.1111/j.1399-3038.2008.00845.x. Epub 2009 Jan 31.
Symptomatic hypogammaglobulinemia in childhood may be the initial finding of primary immunodeficiency (PID) or may be due to delay in maturation of immunoglobulin synthesis. The aim of this study was to review the clinical and laboratory records of patients with unclassified hypogammaglobulinemia and to evaluate whether these children experience changes in serum immunoglobulin concentrations during long-term followup and have an exact diagnosis in natural course of disease. We reviewed the data of 412 patients who were diagnosed as PID with symptomatic hypogammaglobulinemia. Thirty-seven patients with hypogammaglobulinemia [19 males (51.4%) and 18 females (48.6%), with a followup of 34.1 +/- 22.0 months] who were not classified according to European Society for Immunodeficiencies diagnostic criteria were included in this study. The mean age at the beginning of the symptoms was 21.4 +/- 20.6 months and the mean age at admission was 51.5 +/- 25.8 months. The commonest clinical presentations were recurrent upper (94.6%) and/or lower (40.5%) respiratory infections, urinary infection (27%) and gastroenteritis (10.8%). Percentage of consanguinity was 8%. Of the initial 37 patients, 18 (48.6%) spontaneously corrected their immunoglobulin abnormalities during followup. Clinical symptoms of these patients were also improved. IgG, IgA and IgM levels reached to normal levels at ages 62.5 +/- 21.8, 72.0 +/- 11.2, 55.2 +/- 7.8 months, respectively. In remaining 19 patients with undefined/unclassified hypogammaglobulinemia, three partial IgA deficiency, seven IgG subclass deficiency, two selective IgM deficiency and two common variable immunodeficiency (CVID) were diagnosed by long-term monitoring of immunoglobulin levels. Five (13.5%) of the 37 unclassified patients could not be exactly diagnosed while two of them might have a T-cell defect and three of them still had low IgG and IgA levels but adequate antibody responses against vaccine antigens. In conclusion, it is important to monitor symptomatic patients with hypogammaglobulinemia periodically. Some children may spontaneously correct their immunoglobulin abnormalities not in the first 30 months of age, but during the first decade of life and some of them may have a severe PID like CVID.
儿童期症状性低丙种球蛋白血症可能是原发性免疫缺陷（PID）的最初发现，也可能是由于免疫球蛋白合成成熟延迟所致。本研究旨在回顾无分类低丙种球蛋白血症患者的临床和实验室记录，并评估这些儿童在长期随访过程中血清免疫球蛋白浓度是否发生变化，以及在疾病自然病程中是否有明确的诊断。我们回顾了 412 名被诊断为有症状性低丙种球蛋白血症的 PID 患者的数据。37 名低丙种球蛋白血症患者（19 名男性[51.4%]和 18 名女性[48.6%]，随访 34.1±22.0 个月）未按照欧洲免疫缺陷学会的诊断标准进行分类，包括在本研究中。症状开始时的平均年龄为 21.4±20.6 个月，入院时的平均年龄为 51.5±25.8 个月。最常见的临床表现是复发性上呼吸道（94.6%）和/或下呼吸道（40.5%）感染、尿路感染（27%）和胃肠炎（10.8%）。近亲结婚率为 8%。在最初的 37 名患者中，18 名（48.6%）在随访期间自发纠正了免疫球蛋白异常。这些患者的临床症状也有所改善。IgG、IgA 和 IgM 水平分别在 62.5±21.8、72.0±11.2、55.2±7.8 个月时达到正常水平。在未分类的 19 名低丙种球蛋白血症患者中，3 名部分 IgA 缺乏，7 名 IgG 亚类缺乏，2 名选择性 IgM 缺乏，2 名普通可变免疫缺陷（CVID）通过长期监测免疫球蛋白水平得到诊断。在 37 名未分类的患者中，有 5 名（13.5%）无法明确诊断，其中 2 名可能存在 T 细胞缺陷，3 名患者仍存在低 IgG 和 IgA 水平，但对疫苗抗原有足够的抗体反应。总之，定期监测有低丙种球蛋白血症症状的患者非常重要。一些儿童可能不会在 30 个月之前自发纠正免疫球蛋白异常，而是在生命的第一个十年期间，其中一些儿童可能患有严重的 PID，如 CVID。
