Abstract
Hermansky-Pudlak Syndrome (HPS) is a rare, genetic, multisystem disorder characterized by oculocutaneous albinism (OCA), bleeding diathesis, immunodeficiency, granulomatous colitis, and pulmonary fibrosis. HPS pulmonary fibrosis (HPS-PF) occurs in 100% of patients with subtype HPS-1 and has a similar presentation to idiopathic pulmonary fibrosis. Upon onset, individuals with HPS-PF have approximately 3 years before experiencing signs of respiratory failure and eventual death. This review aims to summarize current research on HPS along with its associated pulmonary fibrosis and its implications for the development of novel treatments. We will discuss the genetic basis of the disease, its epidemiology, and current therapeutic and clinical management strategies. We continue to review the cellular processes leading to the development of HPS-PF in alveolar epithelial cells, lymphocytes, mast cells, and fibrocytes, along with the molecular mechanisms that contribute to its pathogenesis and may be targeted in the treatment of HPS-PF. Finally, we will discuss emerging new cellular and molecular approaches for studying HPS, including lentiviral-mediated gene transfer, induced pluripotent stem cells (iPSCs), organoid and 3D-modelling, and CRISPR/Cas9-based gene editing approaches.
Highlights
Hermansky-Pudlak Syndrome (HPS) is a rare, autosomal recessive, multisystem disorder that has a disproportionately high effect on Puerto Ricans (1 in 1800) (Witkop et al, 1990)
The goal of this review is to summarize the current understanding of HPS, focusing on its genetic basis, epidemiology, and current clinical management, along with the cellular and molecular pathways involved in the progression of HPS-pulmonary fibrosis (PF)
For the remaining of this article, we focus on the clinical management strategies of HPS pulmonary fibrosis (HPS-PF), as well as clinical and experimental evidences using cell culture and animal models investigating the pathogenesis of HPS-PF
Summary
Hermansky-Pudlak Syndrome (HPS) is a rare, autosomal recessive, multisystem disorder that has a disproportionately high effect on Puerto Ricans (1 in 1800) (Witkop et al, 1990). This disorder is caused by genetic mutations which result in defective lysosome-related organelles (LROs) such as melanosomes, which synthesize and store melanin, and platelet dense granules, which store small signaling molecules involved in platelet aggregation (Hermansky and Pudlak 1959; Seiji et al, 1963; King and Reed, 2002). Granulomatous colitis, which affects approximately 15% of patients with HPS, has similar clinical and pathological presentations as chronic ulcerative colitis and Crohn’s disease (Huizing et al, 1993; Grucela et al, 2006; Hazzan et al, 2006; Salvaggio et al, 2014)
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