Your browser doesn't support javascript.
loading
Cerebral adrenoleukodystrophy is associated with loss of tolerance to profilin.
Orchard, Paul J; Nascene, David R; Gupta, Ashish; Taisto, Mandy E; Higgins, LeeAnn; Markowski, Todd W; Lund, Troy C.
Afiliação
  • Orchard PJ; Division of Pediatric Blood and Marrow Transplant, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
  • Nascene DR; Department of Diagnostic Radiology, University of Minnesota Medical Center, Minneapolis, MN, USA.
  • Gupta A; Division of Pediatric Blood and Marrow Transplant, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
  • Taisto ME; Division of Pediatric Blood and Marrow Transplant, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
  • Higgins L; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • Markowski TW; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
  • Lund TC; Division of Pediatric Blood and Marrow Transplant, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Eur J Immunol ; 49(6): 947-953, 2019 06.
Article em En | MEDLINE | ID: mdl-30829395
Childhood cerebral adrenoleukodystrophy (cALD) is a devastating manifestation of ALD accompanied by demyelination, inflammation, and blood brain barrier (BBB) disruption with shared characteristics of an auto-immune disease. We utilized plasma samples pre- and postdevelopment of cALD to determine the presence of specific auto-antibodies. Mass spectrometry of protein specifically bound with post-cALD plasma antibody identified Profilin1 (PFN1) as the target. In a screen of 94 boys with cALD 48 (51%) had anti-PFN1 antibodies, whereas only 2/29 boys with ALD but without cerebral disease, and 0/30 healthy controls showed anti-PFN1 immunoreactivity. Cerebral spinal fluid from those with cALD showed higher levels of PFN1 protein compared with non-cALD samples (324 ± 634 versus 42 ± 23 pg/mL, p = 0.04). Boys that were anti-PFN positive had a significant increase in the amount of gadolinium signal observed on MRI when compared to boys that were anti-PFN1 negative (p = 0.04) possibly indicating increased BBB disruption. Anti-PFN1 positivity was also associated with elevated levels of very long chain fatty acids (C26 of 1.12 ± 0.41 versus 0.97 ± 0.30 mg/dL, p = 0.03) and increased plasma BAFF (973 ± 277 versus 733 ± 269 pg/mL, p = 0.03). In conclusion, anti-PFN may be a novel biomarker associated with the development of cALD in boys with ALD.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Autoanticorpos / Autoantígenos / Adrenoleucodistrofia / Profilinas Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Child / Humans / Male Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Autoanticorpos / Autoantígenos / Adrenoleucodistrofia / Profilinas Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Child / Humans / Male Idioma: En Ano de publicação: 2019 Tipo de documento: Article