title: Long time enzyme replacement therapy stabilizes obstructive lung disease and alters peripheral immune cell subsets in Fabry patients.
abstract: BACKGROUND
  Fabry disease is an X-linked lysosomal storage disorder, causing accumulation of globotriaosylceramid in different organs. Glycolipids are activators of different immune cell subsets the resulting inflammation is responsible for organ damage. Pulmonary involvement leads to airway inflammation; however, data on severity, as well as the effect of enzyme replacement therapy on lung function parameters and changes in peripheral immune cell subsets on lung involvement are sparse.
  
  
  METHODS
  Seven Fabry patients and four carriers underwent detailed clinical examinations screening for pulmonary manifestations. Repetitive measurements were performed on five patients on ERT (average follow-up 5 years). Patients with Fabry disease and control volunteers were included into peripheral blood cell measurements.
  
  
  RESULTS
  Lung involvement was present in all patients. Symptoms suggestive for lung disease were mild, however, obstructive ventilatory disorder, dominantly affecting small airways accompanied by hyperinflation was demonstrated in all affected patients. ERT resulted in small improvement of FEV1 in most treated patients. Decreased ratio of myeloid DC, Th17 cells while increase in T helper (Th)1 cells, and no change in Th2 and regulatory T (Treg) cells were detected in Fabry patients.
  
  
  CONCLUSIONS
  Fabry disease results mainly in mild symptoms related to lung involvement, characterized by moderate non-reversible obstructive ventilatory disorder. Stabilization of airway obstruction during follow-up was observed using ERT in most patients, emphasizing the importance of this treatment in respect of pulmonary manifestations. Changes of immune cell subsets in the peripheral blood might play a role in inflammatory process, including small airways in Fabry patient's lung.
authors.affiliation: Department of Pulmonology, Semmelweis University, Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Odler
authors.affiliation: 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Áron
authors.initials: Á
authors.lastname: Cseh
authors.affiliation: 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Constantin
authors.affiliation: 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Fekete
authors.affiliation: Department of Pulmonology, Semmelweis University, Budapest, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Losonczy
authors.affiliation: Department of Pulmonology, Semmelweis University, Budapest, Hungary.
authors.forename: Lilla
authors.initials: L
authors.lastname: Tamási
authors.affiliation: Semmelweis University, Heart and Vascular Center, Budapest, Hungary.
authors.forename: Kálmán
authors.initials: K
authors.lastname: Benke
authors.affiliation: Semmelweis University, Heart and Vascular Center, Budapest, Hungary.|Semmelweis University, MTA-SE Lendület Cardiovascular Imaging Research Group, Heart and Vascular Center, Budapest, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Szilveszter
authors.affiliation: Department of Pulmonology, Semmelweis University, Budapest, Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Müller
mesh_terms: D000328:Adult; D056947:Enzyme Replacement Therapy / Q000379:methods*; D000795:Fabry Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D008168:Lung / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008173:Lung Diseases, Obstructive / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests / Q000379:methods; D013107:Sphingolipids / Q000378:metabolism; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D013107:Sphingolipids
keywords: Fabry disease; dendritic cell; immune cell; lung function; obstructive; pulmonary