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Journal of Inherited Metabolic Disease

, Volume 41, Issue 4, pp 631–640 | Cite as

Evaluation of plasma biomarkers of inflammation in patients with maple syrup urine disease

  • Giselli Scaini
  • Tássia Tonon
  • Carolina F. Moura de Souza
  • Patricia F. Schuck
  • Gustavo C. Ferreira
  • João Quevedo
  • João Seda Neto
  • Tatiana Amorim
  • Jose S. CameloJr
  • Ana Vitoria Barban Margutti
  • Rafael Hencke Tresbach
  • Fernanda Sperb-Ludwig
  • Raquel Boy
  • Paula F. V. de Medeiros
  • Ida Vanessa D. Schwartz
  • Emilio Luiz Streck
Original Article

Abstract

Maple syrup urine disease (MSUD) is an autosomal recessive inherited disorder that affects branched-chain amino acid (BCAA) catabolism and is associated with acute and chronic brain dysfunction. Recent studies have shown that inflammation may be involved in the neuropathology of MSUD. However, these studies have mainly focused on single or small subsets of proteins or molecules. Here we performed a case-control study, including 12 treated-MSUD patients, in order to investigate the plasmatic biomarkers of inflammation, to help to establish a possible relationship between these biomarkers and the disease. Our results showed that MSUD patients in treatment with restricted protein diets have high levels of pro-inflammatory cytokines [IFN-γ, TNF-α, IL-1β and IL-6] and cell adhesion molecules [sICAM-1 and sVCAM-1] compared to the control group. However, no significant alterations were found in the levels of IL-2, IL-4, IL-5, IL-7, IL-8, and IL-10 between healthy controls and MSUD patients. Moreover, we found a positive correlation between number of metabolic crisis and IL-1β levels and sICAM-1 in MSUD patients. In conclusion, our findings in plasma of patients with MSUD suggest that inflammation may play an important role in the pathogenesis of MSUD, although this process is not directly associated with BCAA blood levels. Overall, data reported here are consistent with the working hypothesis that inflammation may be involved in the pathophysiological mechanism underlying the brain damage observed in MSUD patients.

Keywords

Maple syrup urine disease Branched-chain amino acid Inflammation Pro-inflammatory cytokines Cell adhesion molecules 

Notes

Acknowledgements

Laboratory of Bioenergetics (Brazil) is one of the centres of the National Institute for Molecular Medicine (INCT-MM) and one of the members of the Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC). This research was supported by grants from CNPq (402047/2010-9), FAPESC, and UNESC. We are also grateful to INAGEMP (Brazilian National Institute of Population Medical Genetics) for the support provided through grants FAPERGS #17/2551.0000521.0, CNPq #465549/2014-4 and CAPES #88887.136366/2017-00. The authors acknowledge all the members of the Brazilian MSUD Network, especially the LAM- SGM/HCPA group for helping us with the quantitative amino acid analysis as well as Dr. Kevin Strauss and Dr. Erik Puffenberger (Clinical for Special Children, Pennsylvania-USA) for helping us with the alloisoleucine measurement. The authors declare that they have not had any financial, personal or other relationships that have influenced the work.

Details of funding

This research was supported by grants from CNPq (402047/2010-9), FAPESC, and UNESC.

Compliance with ethical standards

Conflict of interest

G. Scaini, T. Tonon, C. F. Moura de Souza, P. F. Schuck, G. C. Ferreira, J. Quevedo, J. S. Neto, T. Amorim, J. S. Camelo Jr, A. V. B. Margutti, R. Tresbach, F. Sperb-Ludwig, R. Boy, P. F. V. de Medeiros, I. V. D. Schwartz, E. L. Streck declare that they have no conflict of interest.

Supplementary material

10545_2018_188_MOESM1_ESM.docx (22 kb)
ESM 1 (DOCX 21 kb)

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Copyright information

© SSIEM 2018

Authors and Affiliations

  • Giselli Scaini
    • 1
  • Tássia Tonon
    • 2
    • 3
  • Carolina F. Moura de Souza
    • 4
  • Patricia F. Schuck
    • 5
  • Gustavo C. Ferreira
    • 6
  • João Quevedo
    • 7
  • João Seda Neto
    • 8
  • Tatiana Amorim
    • 9
  • Jose S. CameloJr
    • 10
  • Ana Vitoria Barban Margutti
    • 10
  • Rafael Hencke Tresbach
    • 2
    • 11
  • Fernanda Sperb-Ludwig
    • 2
    • 11
  • Raquel Boy
    • 12
  • Paula F. V. de Medeiros
    • 13
  • Ida Vanessa D. Schwartz
    • 4
    • 11
  • Emilio Luiz Streck
    • 1
  1. 1.Laboratório de Bioenergética e Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Programa de Pós-Graduação em Ciências da SaúdeUniversidade do Extremo Sul CatarinenseCriciúmaBrazil
  2. 2.BRAIN Laboratory (Basic Research and Advanced Investigations in Neurosciences)Hospital de Clínicas de Porto AlegrePorto AlegreBrazil
  3. 3.Post Graduation Program in Medicine: Medical SciencesUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  4. 4.Medical Genetics ServiceHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  5. 5.Laboratório de Erros Inatos do Metabolismo, Programa de Pós-Graduação em Ciências da SaúdeUniversidade do Extremo Sul CatarinenseCriciúmaBrazil
  6. 6.Laboratório de Neuroquímica, Instituto de Biofísica Carlos ChagasUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  7. 7.Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences UnitUniversity of Southern Santa Catarina (UNESC)CriciúmaBrazil
  8. 8.Hospital Sirio LibanesSão PauloBrazil
  9. 9.Associação de Pais e Amigos dos Excepcionais (APAE)SalvadorBrazil
  10. 10.Pediatrics Department, Ribeirão Preto Medical SchoolUniversity of São PauloRibeirão PretoBrazil
  11. 11.Programa de Pós-Graduação em Genética e Biologia MolecularUniversidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  12. 12.Pediatrics Department, Hospital Universitário Pedro ErnestoUniversidade do Estado do Rio de JaneiroRio de JaneiroBrazil
  13. 13.Unidade Acadêmica de Medicina, Hospital Universitário Alcides Carneiro, Universidade Federal de Campina GrandeCampina GrandeBrazil

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