Age-related neutrophil activation in Hermansky-Pudlak Syndrome Type-1

Age-related neutrophil activation in Hermansky-Pudlak Syndrome Type-1

Abstract Hermansky-Pudlak Syndrome (HPS) type 1 (HPS-1) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet dysfunction, and pulmonary fibrosis (HPS-PF), the leading cause of mortality in these patients. HPS-PF manifests earlier than idiopathic pulmonary fibrosis, t...

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Main Authors: Lourdes Marinna Caro-Rivera, Sonya Malavez-Cajigas, Mercedes Lacourt-Ventura, Andrea P. Rivera-Torres, Dorca E. Marcano-Jiménez, Pablo López-Colon, José Muñiz-Hernández, Enid Rivera-Jiménez, Mónica Egozcue-Dionisi, Rosa Román-Carlo, Wilfredo De Jesús-Rojas, Marcos J. Ramos-Benítez
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Orphanet Journal of Rare Diseases
Online Access:https://doi.org/10.1186/s13023-025-03758-5
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Summary:Abstract Hermansky-Pudlak Syndrome (HPS) type 1 (HPS-1) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet dysfunction, and pulmonary fibrosis (HPS-PF), the leading cause of mortality in these patients. HPS-PF manifests earlier than idiopathic pulmonary fibrosis, typically between 30 and 40 years of age. The etiology and drivers of HPS-PF progression remain poorly understood, and no FDA-approved therapies exist. Neutrophil extracellular traps (NETs) and neutrophil-derived mediators have emerged as key players in fibrosis, promoting lung injury, inflammation, and fibroblast activation. This study evaluates the role of neutrophil activation in age-related changes in patients with HPS-1, focusing on differences in inflammatory markers, neutrophil granules, and NETosis capacity. We observed significantly elevated levels of NETs, neutrophil granule proteins (NE, NGAL, LF), and inflammatory cytokines (IL-8, IL-6) in patients with HPS-1 older than 40 years compared to younger patients and healthy controls. Additionally, fibrosis-related markers (MMP-7 and MMP-8) were significantly higher in older patients. Elevated levels of anandamide (AEA), a circulating marker of HPS-PF, were positively associated with neutrophil granule markers in older patients, suggesting its association with fibrosis. Neutrophils from older patients also demonstrated increased NETosis capacity. These findings suggest that age-related neutrophil activation may contribute to an inflammatory environment that promotes fibrosis progression in HPS-1.
ISSN:1750-1172

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