title: Time of Initiating Enzyme Replacement Therapy Affects Immune Abnormalities and Disease Severity in Patients with Gaucher Disease.
abstract: Gaucher disease (GD) patients often present with abnormalities in immune response that may be the result of alterations in cellular and/or humoral immunity. However, how the treatment and clinical features of patients impact the perturbation of their immunological status remains unclear. To address this, we assessed the immune profile of 26 GD patients who were part of an enzyme replacement therapy (ERT) study. Patients were evaluated clinically for onset of GD symptoms, duration of therapy and validated outcome measures for ERT. According to DS3 disease severity scoring system criteria, they were assigned to have mild, moderate or severe GD. Flow cytometry based immunophenotyping was performed to analyze subsets of T, B, NK, NKT and dendritic cells. GD patients showed multiple types of immune abnormalities associated to T and B lymphocytes with respect to their subpopulations as well as memory and activation markers. Skewing of CD4 and CD8 T cell numbers resulting in lower CD4/CD8 ratio and an increase in overall T cell activation were observed. A decrease in the overall B cells and an increase in NK and NKT cells were noted in the GD patients compared to controls. These immune alterations do not correlate with GD clinical type or level of biomarkers. However, subjects with persistent immune alterations, especially in B cells and DCs correlate with longer delay in initiation of ERT (ΔTX). Thus, while ERT may reverse some of these immune abnormalities, the immune cell alterations become persistent if therapy is further delayed. These findings have important implications in understanding the immune disruptions before and after treatment of GD patients.
authors.affiliation: Lysosomal and Rare Disorders Research and Treatment Center, Fairfax, Virginia, United States of America.|Amerimmune, O and O Alpan, LLC, Fairfax, Virginia, United States of America.
authors.forename: Renuka Pudi
authors.identifier: http://orcid.org/0000-0001-6957-6284
authors.initials: RP
authors.lastname: Limgala
authors.affiliation: Lysosomal and Rare Disorders Research and Treatment Center, Fairfax, Virginia, United States of America.
authors.forename: Chidima
authors.initials: C
authors.lastname: Ioanou
authors.affiliation: Amerimmune, O and O Alpan, LLC, Fairfax, Virginia, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Plassmeyer
authors.affiliation: Amerimmune, O and O Alpan, LLC, Fairfax, Virginia, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Ryherd
authors.affiliation: Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, United States of America.
authors.forename: Lina
authors.initials: L
authors.lastname: Kozhaya
authors.affiliation: Amerimmune, O and O Alpan, LLC, Fairfax, Virginia, United States of America.
authors.forename: Lauren
authors.initials: L
authors.lastname: Austin
authors.affiliation: Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, United States of America.
authors.forename: Cem
authors.initials: C
authors.lastname: Abidoglu
authors.affiliation: Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, United States of America.
authors.forename: Derya
authors.initials: D
authors.lastname: Unutmaz
authors.affiliation: Amerimmune, O and O Alpan, LLC, Fairfax, Virginia, United States of America.
authors.forename: Oral
authors.initials: O
authors.lastname: Alpan
authors.affiliation: Lysosomal and Rare Disorders Research and Treatment Center, Fairfax, Virginia, United States of America.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Goker-Alpan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D056947:Enzyme Replacement Therapy; D005260:Female; D005434:Flow Cytometry; D005776:Gaucher Disease / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D061665:Time-to-Treatment; D016896:Treatment Outcome; D055815:Young Adult