PDF(Pubmed)
Abstract：
BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterized by abnormal accumulation of pulmonary surfactant lipids in alveoli or terminal bronchioles, leading to increased infection risk and progressive respiratory failure. Approximately more than 90% of all cases are autoimmune PAP (aPAP). Since one of the predisposing factors has been identified as genes located within the major-histocompatibility-complex region, an investigation of human leukocyte antigen (HLA) alleles associated with the risk of aPAP is warranted.
METHODS: We retrospectively studied 60 patients pathologically diagnosed with PAP from 2019 to 2022. Patients were divided into the aPAP group or secondary PAP (sPAP) group according to their clinical information. Qualified DNA was extracted from the paraffin-embedded tissue of 28 patients, and the PCR-sequence-based typing method was used for HLA-DRB1 genotyping.
RESULTS: A similar HLA-DRB1 allele profile (including the HLA-DRB1*08:03) between the aPAP group and sPAP group was revealed, except that HLA-DRB1*14:54, which has never been reported in aPAP patients, was only detected in the aPAP group rather than the sPAP group (19.4% vs. 0.0%, p = 0.030). Under inhaled granulocyte-macrophage colony-stimulating factor therapy, more clinical remission was observed in HLA-DRB1*14:54 carriers rather than in HLA-DRB1*08:03 carriers (80.0% vs. 57.1%).
CONCLUSIONS: Our real-world study revealed for the first time that a population with HLA-DRB1*14:54 was subject to aPAP, and HLA-DRB1*14:54 might imply a response in aPAP patients to inhaled granulocyte-macrophage colony-stimulating factor in aPAP patients.
METHODS: We retrospectively studied 60 patients pathologically diagnosed with PAP from 2019 to 2022. Patients were divided into the aPAP group or secondary PAP (sPAP) group according to their clinical information. Qualified DNA was extracted from the paraffin-embedded tissue of 28 patients, and the PCR-sequence-based typing method was used for HLA-DRB1 genotyping.
RESULTS: A similar HLA-DRB1 allele profile (including the HLA-DRB1*08:03) between the aPAP group and sPAP group was revealed, except that HLA-DRB1*14:54, which has never been reported in aPAP patients, was only detected in the aPAP group rather than the sPAP group (19.4% vs. 0.0%, p = 0.030). Under inhaled granulocyte-macrophage colony-stimulating factor therapy, more clinical remission was observed in HLA-DRB1*14:54 carriers rather than in HLA-DRB1*08:03 carriers (80.0% vs. 57.1%).
CONCLUSIONS: Our real-world study revealed for the first time that a population with HLA-DRB1*14:54 was subject to aPAP, and HLA-DRB1*14:54 might imply a response in aPAP patients to inhaled granulocyte-macrophage colony-stimulating factor in aPAP patients.
摘要：
背景：肺泡蛋白沉积症（PAP）是一种罕见的肺部疾病，其特征是肺泡或终末细支气管中肺表面活性物质脂质的异常积累，导致感染风险增加和进行性呼吸衰竭。所有病例中大约90%以上是自身免疫性PAP(aPAP)。由于其中一个诱发因素已被鉴定为位于主要组织相容性复合体区域内的基因，有必要对与aPAP风险相关的人类白细胞抗原(HLA)等位基因进行研究.
方法：我们回顾性研究了2019年至2022年经病理诊断为PAP的60例患者。根据患者的临床信息将患者分为aPAP组和继发性PAP（sPAP）组。从28名患者的石蜡包埋组织中提取合格的DNA，并使用基于PCR序列的分型方法进行HLA-DRB1基因分型。
结果：显示了aPAP组和sPAP组之间相似的HLA-DRB1等位基因谱（包括HLA-DRB1*08:03），除了HLA-DRB1*14:54，这在aPAP患者中从未报道过，仅在aPAP组而不是sPAP组中检测到(19.4%vs.0.0%,p=0.030)。在吸入粒细胞-巨噬细胞集落刺激因子治疗下，在HLA-DRB1*14:54携带者中观察到更多的临床缓解，而不是HLA-DRB1*08:03携带者(80.0%vs.57.1%）。
结论：我们的真实世界研究首次揭示HLA-DRB1*14:54的人群受到aPAP的影响，和HLA-DRB1*14:54可能暗示aPAP患者对aPAP患者吸入粒细胞-巨噬细胞集落刺激因子的反应。
方法：我们回顾性研究了2019年至2022年经病理诊断为PAP的60例患者。根据患者的临床信息将患者分为aPAP组和继发性PAP（sPAP）组。从28名患者的石蜡包埋组织中提取合格的DNA，并使用基于PCR序列的分型方法进行HLA-DRB1基因分型。
结果：显示了aPAP组和sPAP组之间相似的HLA-DRB1等位基因谱（包括HLA-DRB1*08:03），除了HLA-DRB1*14:54，这在aPAP患者中从未报道过，仅在aPAP组而不是sPAP组中检测到(19.4%vs.0.0%,p=0.030)。在吸入粒细胞-巨噬细胞集落刺激因子治疗下，在HLA-DRB1*14:54携带者中观察到更多的临床缓解，而不是HLA-DRB1*08:03携带者(80.0%vs.57.1%）。
结论：我们的真实世界研究首次揭示HLA-DRB1*14:54的人群受到aPAP的影响，和HLA-DRB1*14:54可能暗示aPAP患者对aPAP患者吸入粒细胞-巨噬细胞集落刺激因子的反应。
