Revisiting double-negative T cells in autoimmune lymphoproliferative immunodeficiencies: a case series.

IF 2.5 4区医学 Q3 ALLERGY Allergologia et immunopathologia Pub Date : 2024-09-01 eCollection Date: 2024-01-01 DOI:10.15586/aei.v52i5.1115

Mahnaz Jamee, Samin Sharafian, Narges Eslami, Shideh Namazi Bayegi, Mohammad Keramatipour, Mohamad Nabavi, Sima Shokri, Marjan Shakiba, Bibi Shahin Shamsian, Hassan Abolghasemi, Kurosh Vahidshahi, Ghamartaj Khanbabaee, Shahnaz Armin, Zahra Chavoshzadeh, Mehrnaz Mesdaghi

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Abstract

Background: Elevated level of double-negative T (DNT) cells is a historical hallmark of autoimmune lymphoproliferative syndrome (ALPS) diagnosis. However, the peripheral blood level of DNT cells might also be compromised in autoimmune lymphoproliferative immunodeficiencies (ALPID) other than ALPS, inattention to which would increase the delay in diagnosis of the underlying genetic defect and hinder disease-specific treatment.

Materials and methods: This cross-sectional study recruited patients suffering from ALPID (exclusion of ALPS) with established genetic diagnosis. Following thorough history taking, immunophenotyping for lymphocyte subsets was performed using BD FACS CaliburTM flowcytometry.

Results: Fifteen non-ALPS ALPID patients (60% male and 40% female) at a median (interquartile range: IQR) age of 14.0 (7.6-21.8) years were enrolled. Parental consanguinity and family history of immunodeficiency were present in 8 (53.3%) patients. The median (IQR) age at first presentation, clinical and molecular diagnosis were 18 (4-36) months, 8.0 (4.0-17.0) years, and 9.5 (5.0-20.9) years, respectively. Molecular defects were observed in these genes: LRBA (3, 20%), CTLA-4 (2, 13.3%), BACH2 (2, 13.3%), AIRE (2, 13.3%), and FOXP3, IL2Rβ, DEF6, RASGRP1, PIK3CD, and PIK3R1 each in one patient (6.7%). The most common manifestations were infections (14, 93.3%), autoimmunity (12, 80%), and lymphoproliferation (10, 66.7%). The median (IQR) count of white blood cells (WBCs) and lymphocytes were 7160 (3690-12,600) and 3266 (2257-5370) cells/mm3, respectively. The median (IQR) absolute counts of CD3+ T lymphocytes and DNTs were 2085 (1487-4222) and 18 (11-36) cells/mm3, respectively. Low lymphocytes and low CD3+ T cells were observed in 3 (20%) patients compared to normal age ranges. Only one patient with FOXP3 mutation had DNT cells higher than the normal range for age.

Conclusions: Most non-ALPS ALPID patients manifested normal DNT cell count. For a small subgroup of patients with high DNT cells, defects in other IEI genes may explain the phenotype and should be included in the diagnostic genetic panel.

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重新审视自身免疫性淋巴细胞增生性免疫缺陷症中的双阴性 T 细胞：一个病例系列。

背景：双阴性T细胞（DNT）水平升高是自身免疫性淋巴组织增生综合征（ALPS）诊断的一个历史性标志。然而，在 ALPS 以外的自身免疫性淋巴细胞增生性免疫缺陷症（ALPID）中，外周血 DNT 细胞水平也可能受到影响：这项横断面研究招募了已确定基因诊断的 ALPID 患者（不包括 ALPS）。在详细询问病史后，使用 BD FACS CaliburTM 流式细胞仪对淋巴细胞亚群进行免疫分型：结果：15 名非 ALPS ALPID 患者（60% 为男性，40% 为女性）入组，中位数（四分位数间距：IQR）年龄为 14.0（7.6-21.8）岁。8名患者（53.3%）的父母有血缘关系和免疫缺陷家族史。首次发病、临床诊断和分子诊断的中位年龄（IQR）分别为18（4-36）个月、8.0（4.0-17.0）岁和9.5（5.0-20.9）岁。在这些基因中观察到了分子缺陷：LRBA（3 例，占 20%）、CTLA-4（2 例，占 13.3%）、BACH2（2 例，占 13.3%）、AIRE（2 例，占 13.3%），以及 FOXP3、IL2Rβ、DEF6、RASGRP1、PIK3CD 和 PIK3R1 各 1 例（占 6.7%）。最常见的表现是感染（14 例，93.3%）、自身免疫（12 例，80%）和淋巴增生（10 例，66.7%）。白细胞和淋巴细胞的中位数（IQR）分别为7160（3690-12600）个/mm3和3266（2257-5370）个/mm3。CD3+ T 淋巴细胞和 DNT 绝对计数的中位数（IQR）分别为 2085（1487-4222）和 18（11-36）个细胞/mm3。与正常年龄段相比，3 名患者（20%）的淋巴细胞和 CD3+ T 细胞数量偏低。只有一名FOXP3突变患者的DNT细胞高于正常年龄范围：大多数非 ALPS ALPID 患者的 DNT 细胞数量正常。对于一小部分 DNT 细胞数偏高的患者，其他 IEI 基因的缺陷可能是表型的原因，应将其纳入基因诊断面板。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Allergologia et immunopathologia 医学-过敏

CiteScore

3.70

自引率

0.00%

发文量

131

审稿时长

6-12 weeks

期刊介绍： Founded in 1972 by Professor A. Oehling, Allergologia et Immunopathologia is a forum for those working in the field of pediatric asthma, allergy and immunology. Manuscripts related to clinical, epidemiological and experimental allergy and immunopathology related to childhood will be considered for publication. Allergologia et Immunopathologia is the official journal of the Spanish Society of Pediatric Allergy and Clinical Immunology (SEICAP) and also of the Latin American Society of Immunodeficiencies (LASID). It has and independent international Editorial Committee which submits received papers for peer-reviewing by international experts. The journal accepts original and review articles from all over the world, together with consensus statements from the aforementioned societies. Occasionally, the opinion of an expert on a burning topic is published in the "Point of View" section. Letters to the Editor on previously published papers are welcomed. Allergologia et Immunopathologia publishes 6 issues per year and is included in the major databases such as Pubmed, Scopus, Web of Knowledge, etc.