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抗磷脂综合征患者中HLA-DRB1等位基因的分布及其与抗磷脂抗体存在情况和损伤指标的关联。

Distribution of HLA-DRB1 Alleles in Patients With Antiphospholipid Syndrome and Their Association With Antiphospholipid Antibodies Presence and Damage Indexes.

作者信息

Haladyj Ewa, Stypinska Barbara, Matusiewicz Agata, Olesinska Marzena, Paradowska-Gorycka Agnieszka

机构信息

Eli Lilly and Company, Indianapolis, USA.

Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw 02-637, Poland.

出版信息

J Immunol Res. 2025 Mar 24;2025:2827348. doi: 10.1155/jimr/2827348. eCollection 2025.

Abstract

Antiphospholipid syndrome (APS) is frequently coexisting with systemic lupus erythematosus (SLE) and the knowledge on its genetic background is essential. The objective of this work was to assess distribution of human leukocyte antigen (HLA)-DRB1 alleles in patients with APS with or without SLE in the context of Polish population data. The study was performed in a group of 112 patients with APS and healthy subjects to assess the distribution of HLA-DRB1 alleles in patients with APS and their association with clinical characteristics of patients with APS-antiphospholipid antibodies (aPLs) presence and disease activity/damage indexes. The distribution of HLA-DRB1 alleles showed significant differences between patients with APS and healthy subjects. Allelic variant HLA-DRB1 1.15 was identified as risk alleles for APS observed in patients with APS (odds ratio (OR): 2.06 (1.27, 3.23), =0, 004), while HLA-DRB1 1.07 showed significant protective association (OR: 0.37 (0.14-0.76), =0, 006). In subgroup of patients with coexisting SLE allelic variants above were not identified as risk or protective, while protective association was described for HLA-DRB1 01, but not for patients in primary APS group. Presence of antibodies anti- -glycoprotein-I (a GPI) IgA and against domain 1, anti-phosphatidylserine/prothrombin (aPS/PT) and anticardiolipin antibody (aCL) IgA all the antibodies which were negatively associated with HLA-DRB1 15.01 carriers, what was reported for the first time may be suitable in discussion about value of these antibodies in practice and scientific research. This study clearly shows that primary APS has a distinct HLA-DRB1 associations as compared with SLE with a strong positive association with HLA-DRB1 15.01 allele and a protective association with HLA-DRB1 07.01.

摘要

抗磷脂综合征(APS)常与系统性红斑狼疮(SLE)共存,了解其遗传背景至关重要。本研究旨在根据波兰人群数据评估有无SLE的APS患者中人类白细胞抗原(HLA)-DRB1等位基因的分布情况。该研究纳入了112例APS患者和健康受试者,以评估APS患者中HLA-DRB1等位基因的分布及其与APS患者临床特征(抗磷脂抗体(aPLs)的存在以及疾病活动/损伤指数)的关联。APS患者与健康受试者之间HLA-DRB1等位基因的分布存在显著差异。等位基因变体HLA-DRB1 1.15被确定为APS患者中观察到的APS风险等位基因(优势比(OR):2.06(1.27,3.23),P = 0.004),而HLA-DRB1 1.07显示出显著的保护关联(OR:0.37(0.14 - 0.76),P = 0.006)。在合并SLE的患者亚组中,上述等位基因变体未被确定为风险或保护性等位基因,而HLA-DRB1 01显示出保护关联,但原发性APS组患者未出现此情况。抗β2糖蛋白-I(aβ2GPI)IgA抗体、抗结构域1抗体、抗磷脂酰丝氨酸/凝血酶原(aPS/PT)抗体和抗心磷脂抗体(aCL)IgA的存在均与HLA-DRB1 15.01携带者呈负相关,这是首次报道,可能适用于讨论这些抗体在实践和科研中的价值。本研究清楚地表明与SLE相比,原发性APS具有独特的HLA-DRB1关联,与HLA-DRB1 15.01等位基因呈强正相关,与HLA-DRB1 07.01呈保护关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb0/11957857/1f7ec864ae93/JIR2025-2827348.001.jpg

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