Open AccessMonocyte biomarkers define sargramostim treatment outcomes for Parkinson's disease
Author(s) -
Abdelmoaty Mai M.,
Machhi Jatin,
Yeapuri Pravin,
Shahjin Farah,
Kumar Vikas,
Olson Katherine E.,
Mosley R. Lee,
Gendelman Howard E.
Publication year - 2022
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.958
Subject(s) - medicine , innate immune system , immunology , monocyte , immune system , biomarker , biology , biochemistry
Background Dysregulation of innate and adaptive immunity heralds both the development and progression of Parkinson's disease (PD). Deficits in innate immunity in PD are defined by impairments in monocyte activation, function, and pro‐inflammatory secretory factors. Each influences disease pathobiology. Methods and Results To define monocyte biomarkers associated with immune transformative therapy for PD, changes in gene and protein expression were evaluated before and during treatment with recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF, sargramostim, Leukine ® ). Monocytes were recovered after leukapheresis and isolation by centrifugal elutriation, before and 2 and 6 months after initiation of treatment. Transcriptome and proteome biomarkers were scored against clinical motor functions. Pathway enrichments from single cell‐RNA sequencing and proteomic analyses from sargramostim‐treated PD patients demonstrate a neuroprotective signature, including, but not limited to, antioxidant, anti‐inflammatory, and autophagy genes and proteins (LRRK2, HMOX1, TLR2, TLR8, RELA, ATG7, and GABARAPL2). Conclusions This monocyte profile provides an “early” and unique biomarker strategy to track clinical immune‐based interventions, but requiring validation in larger case studies.