波兰儿科患者原发性噬血细胞淋巴组织细胞病的分子遗传学多样性

IF 2.9 4区 医学 Q3 IMMUNOLOGY Archivum Immunologiae et Therapiae Experimentalis Pub Date : 2021-10-22 DOI:10.1007/s00005-021-00635-4
Katarzyna Bąbol-Pokora, Magdalena Wołowiec, Katarzyna Popko, Aleksandra Jaworowska, Yenan T. Bryceson, Bianca Tesi, Jan-Inge Henter, Wojciech Młynarski, Wanda Badowska, Walentyna Balwierz, Katarzyna Drabko, Krzysztof Kałwak, Lucyna Maciejka-Kembłowska, Anna Pieczonka, Grażyna Sobol-Milejska, Sylwia Kołtan, Iwona Malinowska, for the Polish Pediatric Hematology, Oncology Society
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引用次数: 3

摘要

吞噬血淋巴组织细胞增多症(HLH)是一种由过度、长期和无效的免疫反应引起的危及生命的炎症的临床综合征。在波兰,HLH病例的数量越来越多,但家族性HLH(FHL)的遗传原因尚未报道。我们调查了符合HLH标准的儿科患者的分子遗传学和相关结果。我们研究了54名HLH患者,其中36人接受了基因研究。对25名患者进行了PRF1、UNC13D、STX11、XIAP和SH2D1A基因的直接测序。此外,11名患者接受了靶向下一代测序。在我们的研究组中,17名患者(31%)被诊断为原发性HLH,在13名患者(36%)中发现了双等位基因FHL变体,而在4名患有X连锁淋巴增生性疾病的患者中发现了半合子改变。此外,一名患者被诊断为X连锁免疫缺陷,伴有镁缺陷、EB病毒感染和半合子MAGT1变体引起的肿瘤形成;另一名新生儿被诊断为MVK变异引起的自身炎症综合征。大多数(65%)FHL患者携带UNC13D致病性变体,而PRF1变体发生在两名患者中。在UNC13D、PRF1和XIAP中检测到新的变体。爱泼斯坦-巴尔病毒是23例(65%)继发性HLH患者中最常见的诱因。在3例继发性HLH患者中,发现FHL基因的杂合变异。整个研究组的总生存率为74%,中位随访时间为3.6年。我们的研究结果突出了波兰原发性HLH分子病因的多样性。
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Molecular Genetics Diversity of Primary Hemophagocytic Lymphohistiocytosis among Polish Pediatric Patients

Hemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome of life-threatening inflammation caused by an excessive, prolonged and ineffective immune response. An increasing number of HLH cases is recognized in Poland, but the genetic causes of familial HLH (FHL) have not been reported. We investigated the molecular genetics and associated outcomes of pediatric patients who met HLH criteria. We studied 54 patients with HLH, 36 of whom received genetic studies. Twenty-five patients were subjected to direct sequencing of the PRF1, UNC13D, STX11, XIAP and SH2D1A genes. Additionally, 11 patients were subjected to targeted next-generation sequencing. In our study group, 17 patients (31%) were diagnosed with primary HLH, with bi-allelic FHL variants identified in 13 (36%) patients whereas hemizygous changes were identified in 4 patients with X-linked lymphoproliferative diseases. In addition, one patient was diagnosed with X-linked immunodeficiency with magnesium defect, Epstein–Barr virus infection and neoplasia due to a hemizygous MAGT1 variant; another newborn was diagnosed with auto-inflammatory syndrome caused by MVK variants. The majority (65%) of FHL patients carried UNC13D pathogenic variants, whereas PRF1 variants occurred in two patients. Novel variants in UNC13D, PRF1 and XIAP were detected. Epstein–Barr virus was the most common trigger noted in 23 (65%) of the patients with secondary HLH. In three patients with secondary HLH, heterozygous variants of FHL genes were found. Overall survival for the entire study group was 74% with a median of 3.6 years of follow-up. Our results highlight the diversity of molecular causes of primary HLH in Poland.

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来源期刊
CiteScore
5.90
自引率
0.00%
发文量
26
审稿时长
>12 weeks
期刊介绍: Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is a bimonthly, multidisciplinary journal. It publishes reviews and full original papers dealing with immunology, experimental therapy, immunogenetics, transplantation, microbiology, immunochemistry and ethics in science.
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