Abstract：
UNASSIGNED: LPS-responsive beige-like anchor (LRBA) deficiency is one of the most common monogenic disorders causing common variable immunodeficiency (CVID) and CVID-like disorders. However, the clinical spectrum of compound heterozygous (CHZ) LRBA variation should be extended. In this study, we presented five cases of compound heterozygous LRBA with various refractory cytopenias.
UNASSIGNED: Retrospective analysis of the clinical manifestations, management, and outcomes of five cases (from five pedigrees) with LRBA gene CHZ variants which initially manifested as single/multilineage immune cytopenias was performed.
UNASSIGNED: 1. Gene variations: All five patients inherited the compound heterozygous LRBA variations from their parents which were thought to be pathogenic. BEACH, DUF4704, and LamG were the main affected domains of LRBA gene in this case series. 2. Immune dysregulation of clinic: (1) Hypogammaglobulinemia were recorded in four patients, and the proportion of Treg was decreased in two patients. Only one patient had been with increased TCRαβ+CD4/CD8 double-negative T cells (DNT). (2) Lymphoproliferative manifestations were seen in three patients. (3) All five patients were complained with cytopenia, although they showed different clinical manifestations. None of the parents was asymptomatic. (4) Other immune disorders: P5 also had relapsed infections and autoimmune endocrinopathy. 3. Management and outcomes: P1 and P5 responded well to immunomodulatory therapy and P3 was effectively treated with hemophagocytic lymphohistiocytosis (HLH) first-line regimen chemotherapy. P4 showed no responses to steroids and IVIG. However, TPO-R agonist was effective.
UNASSIGNED: Unlike homozygous mutations, compound heterozygous LRBA variation should always be kept in mind for the various phenotypes and different treatment responses.
UNASSIGNED: Retrospective analysis of the clinical manifestations, management, and outcomes of five cases (from five pedigrees) with LRBA gene CHZ variants which initially manifested as single/multilineage immune cytopenias was performed.
UNASSIGNED: 1. Gene variations: All five patients inherited the compound heterozygous LRBA variations from their parents which were thought to be pathogenic. BEACH, DUF4704, and LamG were the main affected domains of LRBA gene in this case series. 2. Immune dysregulation of clinic: (1) Hypogammaglobulinemia were recorded in four patients, and the proportion of Treg was decreased in two patients. Only one patient had been with increased TCRαβ+CD4/CD8 double-negative T cells (DNT). (2) Lymphoproliferative manifestations were seen in three patients. (3) All five patients were complained with cytopenia, although they showed different clinical manifestations. None of the parents was asymptomatic. (4) Other immune disorders: P5 also had relapsed infections and autoimmune endocrinopathy. 3. Management and outcomes: P1 and P5 responded well to immunomodulatory therapy and P3 was effectively treated with hemophagocytic lymphohistiocytosis (HLH) first-line regimen chemotherapy. P4 showed no responses to steroids and IVIG. However, TPO-R agonist was effective.
UNASSIGNED: Unlike homozygous mutations, compound heterozygous LRBA variation should always be kept in mind for the various phenotypes and different treatment responses.
摘要：
未经证实：LPS反应性米色锚点（LRBA）缺乏症是引起常见可变免疫缺陷（CVID）和CVID样疾病的最常见单基因疾病之一。然而,复合杂合（CHZ）LRBA变异的临床范围应扩大。在这项研究中,我们介绍了5例复合杂合LRBA伴各种难治性血细胞减少症。
UNASSIGNED:临床表现的回顾性分析，管理,并对5例(来自5个家系)LRBA基因CHZ变异最初表现为单/多谱系免疫性血细胞减少症的病例进行了分析。
未经评估：1.基因变异：所有5名患者均从其父母那里继承了复合杂合LRBA变异，被认为是致病性的。海滩,在本病例系列中，DUF4704和LamG是LRBA基因的主要受影响结构域。2.临床免疫失调：（1）4例患者出现低丙种球蛋白血症，2例患者Treg比例降低。只有一名患者的TCRαβ+CD4/CD8双阴性T细胞（DNT）增加。(2)3例患者均有淋巴增生表现。(3)5例患者均为血细胞减少,尽管它们表现出不同的临床表现。父母都没有无症状。（4）其他免疫性疾病：P5也有复发性感染和自身免疫性内分泌病。3.治疗和结果：P1和P5对免疫调节治疗反应良好，P3采用噬血细胞性淋巴组织细胞增生症（HLH）一线方案化疗有效。P4对类固醇和IVIG没有反应。然而,TPO-R激动剂是有效的。
未经证实：与纯合突变不同，对于各种表型和不同的治疗反应，应始终牢记复合杂合LRBA变异。
UNASSIGNED:临床表现的回顾性分析，管理,并对5例(来自5个家系)LRBA基因CHZ变异最初表现为单/多谱系免疫性血细胞减少症的病例进行了分析。
未经评估：1.基因变异：所有5名患者均从其父母那里继承了复合杂合LRBA变异，被认为是致病性的。海滩,在本病例系列中，DUF4704和LamG是LRBA基因的主要受影响结构域。2.临床免疫失调：（1）4例患者出现低丙种球蛋白血症，2例患者Treg比例降低。只有一名患者的TCRαβ+CD4/CD8双阴性T细胞（DNT）增加。(2)3例患者均有淋巴增生表现。(3)5例患者均为血细胞减少,尽管它们表现出不同的临床表现。父母都没有无症状。（4）其他免疫性疾病：P5也有复发性感染和自身免疫性内分泌病。3.治疗和结果：P1和P5对免疫调节治疗反应良好，P3采用噬血细胞性淋巴组织细胞增生症（HLH）一线方案化疗有效。P4对类固醇和IVIG没有反应。然而,TPO-R激动剂是有效的。
未经证实：与纯合突变不同，对于各种表型和不同的治疗反应，应始终牢记复合杂合LRBA变异。
