Evaluation of plasma biomarkers of inflammation in patients with maple syrup urine disease
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.
KeywordsMaple syrup urine disease Branched-chain amino acid Inflammation Pro-inflammatory cytokines Cell adhesion molecules
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.
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