LPS-responsive beige-like anchor (LRBA) deficiency is an autosomal recessive primary immunodeficiency disorder, OMIM (#614700). LRBA deficiency patients suffer from variable manifestations including recurrent infections, immune dysregulation, autoimmunity, cytopenias, and enteropathy. This study describes different clinical phenotypes and immunological characteristics of 18 LRBA deficiency patients diagnosed from Egypt. T and B lymphocyte subpopulations, LRBA, and cytotoxic T lymphocyte-associated protein 4 (CTLA4) expression were evaluated in resting and stimulated T cells using flow cytometry. Next-generation sequencing was used to identify mutations in the LRBA gene. LRBA deficiency patients had significantly lower B cells and increased percentage of memory T cells. CTLA4 levels were lower in LRBA-deficient T regulatory cells in comparison to healthy donors at resting conditions and significantly increased upon stimulation of T cells. We identified 11 novel mutations in LRBA gene ranging from large deletions to point mutations. Finally, we were able to differentiate LRBA-deficient patients from healthy control and common variable immunodeficiency patients using a simple flow cytometry test performed on whole blood and without need to prior stimulation. LRBA deficiency has heterogeneous phenotypes with poor phenotype-genotype correlation since the same mutation may manifest differently even within the same family. Low LRBA expression, low numbers of B cells, increased numbers of memory T cells, and defective CTLA4 expression (which increase to normal level upon T cell stimulation) are useful laboratory tests to establish the diagnosis of LRBA deficiency. Screening of the siblings of affected patients is very important as patients may be asymptomatic at the beginning of the disease course.

LPS 反应性米色样锚 (LRBA) 缺陷是一种常染色体隐性原发性免疫缺陷病，OMIM (#614700)。LRBA 缺乏症患者有多种表现，包括反复感染、免疫失调、自身免疫、血细胞减少和肠病。本研究描述了来自埃及的 18 名 LRBA 缺乏症患者的不同临床表型和免疫学特征。使用流式细胞术在静息和刺激的 T 细胞中评估 T 和 B 淋巴细胞亚群、LRBA 和细胞毒性 T 淋巴细胞相关蛋白 4 (CTLA4) 的表达。下一代测序用于鉴定LRBA 中的突变基因。LRBA 缺乏症患者的 B 细胞显着降低，记忆 T 细胞的百分比增加。与休息条件下的健康供体相比，LRBA 缺陷的 T 调节细胞中的 CTLA4 水平较低，并且在刺激 T 细胞后显着增加。我们在LRBA 中发现了 11 个新突变基因范围从大的缺失到点突变。最后，我们能够使用对全血进行的简单流式细胞术测试将 LRBA 缺陷患者与健康对照和常见可变免疫缺陷患者区分开来，无需事先刺激。LRBA 缺陷具有异质表型，表型-基因型相关性较差，因为即使在同一家族中，相同的突变也可能表现不同。低 LRBA 表达、低 B 细胞数量、记忆性 T 细胞数量增加和 CTLA4 表达缺陷（在 T 细胞刺激后增加到正常水平）是确定 LRBA 缺乏症诊断的有用实验室测试。筛查受影响患者的兄弟姐妹非常重要，因为患者在病程开始时可能没有症状。