Purpose

DiGeorge syndrome has substantial heterogeneity with variable immune deficiency and dysregulation. Implicated immunopathology includes reduced thymic output and increased peripheral homeostatic proliferation with Th2 skewing and expansion of self-reactive cells. We hypothesized that T cell lymphopenia severity will be associated with higher odds of autoimmunity and/or asthma.

Methods

Using the US Immunodeficiency Network registry, we identified patients with 22q11.2 deletion (and/or TBX1). Initial absolute CD3+ T cell values were stratified: normal, 50–99% and below 50% of the lower limit of age-adjusted normal values. Patients with and without reported autoimmunity and asthma were compared using chi-square tests and multivariate logistic regression.

Results

Among 415 patients, autoimmunity was reported in 17 (4.1%), and asthma was reported in 28 (6.7%). Compared with those with no reported autoimmunity, patients with reported autoimmunity more frequently had low CD19+ B cells [3.3% (12/364) vs 28.6% (4/14); p = 0.002] and low IgG [6.2% (20/321) vs 29.4% (5/17); p = 0.005] levels. There were no statistically significant differences in other immune characteristics among those with and without reported asthma. Patients with absolute CD3 levels below 50% of age-adjusted normal values had higher odds of reported autoimmunity (n = 319, OR = 7.56, 95% CI = 1.58–36.17, p = 0.01) and reported asthma (n = 319, OR = 4.5, 95% CI = 1.06–18.93, p = 0.04) as compared with those with normal CD3 values, adjusted for age and low IgG.

Conclusions

Absolute CD3+ T cell counts below 50% of age-adjusted normal values may be associated with higher odds of autoimmunity and/or asthma in patients with DiGeorge syndrome and be potentially useful to identify higher-risk patients.

中文翻译：

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DiGeorge 综合征（22q11.2 缺失和/或相关 TBX1 突变）患者 T 细胞淋巴细胞减少症严重程度与免疫失调之间的关系：一项 USIDNET 研究。

目的

DiGeorge 综合征具有显着的异质性，具有多种免疫缺陷和失调。相关的免疫病理学包括胸腺输出减少和外周稳态增殖增加，Th2 偏斜和自我反应细胞的扩增。我们假设 T 细胞淋巴细胞减少症的严重程度将与更高的自身免疫和/或哮喘几率相关。

方法

使用美国免疫缺陷网络登记处，我们确定了 22q11.2 缺失（和/或 TBX1）的患者。对初始绝对 CD3+ T 细胞值进行分层：正常、50-99% 和低于年龄调整正常值下限的 50%。使用卡方检验和多变量逻辑回归比较有和没有报告自身免疫和哮喘的患者。

结果

在 415 名患者中，17 名（4.1%）报告了自身免疫，28 名（6.7%）报告了哮喘。与未报告自身免疫的患者相比，报告自身免疫的患者 CD19+ B 细胞水平较低 [3.3% (12/364) vs 28.6% (4/14)；p  = 0.002] 和低 IgG [6.2% (20/321) vs 29.4% (5/17)；p  = 0.005] 水平。有和没有报告哮喘的人在其他免疫特征方面没有统计学上的显着差异。绝对 CD3 水平低于年龄调整正常值 50% 的患者报告自身免疫（n  = 319，OR = 7.56，95% CI = 1.58-36.17，p  = 0.01）和报告哮喘（n  = 319，OR = 4.5, 95% CI = 1.06–18.93, p = 0.04) 与具有正常 CD3 值的那些相比，调整了年龄和低 IgG。

结论

绝对 CD3+ T 细胞计数低于年龄调整后正常值的 50% 可能与 DiGeorge 综合征患者的自身免疫和/或哮喘发病率较高有关，并且可能有助于识别高危患者。