Department of Pediatrics, Jeroen Bosch Hospital, `s-Hertogenbosch, the Netherlands.
Scand J Immunol. 2011 Nov;74(5):502-10. doi: 10.1111/j.1365-3083.2011.02609.x.
Age-matched reference values are generally presented with 5th and 95th percentiles as 'normal' reference range. However, they are mostly determined in relatively small groups, which renders this presentation inaccurate. We determined reference values for B-lymphocyte subpopulations in healthy children with the statistical method of tolerance intervals that deals far better with the relatively small numbers tested, and compared these to the cut-off values used in the currently used EUROclass classification for common variable immunodeficiency disorders (CVID) in children. CVID is a heterogeneous group of primary immunodeficiency diseases characterized by low serum immunoglobulin levels and inadequate response to vaccination. Disease-modifying heterozygous amino acid substitutions in TACI are found in around ±10% of CVID patients. Interestingly, we found that age is the primary determinant of TACI-expression on B-lymphocytes, independent of switched memory B-lymphocyte numbers. Immunophenotyping of B-lymphocyte subpopulations is increasingly used to classify patients with CVID into subgroups with different clinical prognosis according to the composition of their B-lymphocyte compartment. These classifications were mainly developed with data obtained in adults. Because of the maturing paediatric immune system, they may not be equally applicable in children: our and other age-matched reference values show great changes in the composition of the B-lymphocyte compartment during development. Although the greatest changes in B-lymphocyte subpopulations occur below the age of 2 years, when the diagnosis of CVID cannot yet be made, it is likely that a classification developed in adults cannot be used to classify the prognosis of children.
年龄匹配的参考值通常以第 5 个和第 95 个百分位数表示为“正常”参考范围。然而，它们大多是在相对较小的群体中确定的，这使得这种表示方式不准确。我们使用容忍区间的统计方法确定了健康儿童 B 淋巴细胞亚群的参考值，该方法可以更好地处理测试的相对较小数量，并将这些参考值与目前用于儿童常见可变免疫缺陷疾病（CVID）的 EUROclass 分类中使用的截止值进行比较。CVID 是一组异质性原发性免疫缺陷疾病，其特征是血清免疫球蛋白水平低，疫苗接种反应不足。TACI 中的杂合氨基酸取代改变约占 CVID 患者的±10%。有趣的是，我们发现年龄是 B 淋巴细胞上 TACI 表达的主要决定因素，与转换记忆 B 淋巴细胞数量无关。B 淋巴细胞亚群的免疫表型分析越来越多地用于根据 B 淋巴细胞池的组成将 CVID 患者分为具有不同临床预后的亚组。这些分类主要是使用成年人获得的数据开发的。由于儿童免疫系统的成熟，它们在儿童中可能并不完全适用：我们和其他年龄匹配的参考值显示 B 淋巴细胞池的组成在发育过程中发生了很大变化。尽管 B 淋巴细胞亚群的最大变化发生在 2 岁以下，此时无法诊断 CVID，但很可能成年人开发的分类不能用于分类儿童的预后。
