Derrick Blackmore1, Liang Li2, Nan Wang2, Walter Maksymowych3, Elaine Yacyshyn4, Zaeem A Siddiqi5. 1. Division of Neurology, University of Alberta, 7th Floor, Clinical Sciences Building, 11350 - 83 Ave NW, Edmonton, AB, T6G 2G3, Canada. 2. Department of Chemistry, University of Alberta, Chemistry Centre Room W3-39C, Edmonton, AB, T6G 2G2, Canada. 3. 568A Heritage Medical Research Centre, University of Alberta, Edmonton, AB, T6G 2S2, Canada. 4. Division of Rheumatology, University of Alberta, 8-130 Clinical Sciences Building, 11350 - 83 Ave NW, Edmonton, AB, Canada. 5. Division of Neurology, University of Alberta, 7th Floor, Clinical Sciences Building, 11350 - 83 Ave NW, Edmonton, AB, T6G 2G3, Canada. zsiddiqi@ualberta.ca.
Abstract
INTRODUCTION: Myasthenia gravis (MG) and rheumatoid arthritis (RA) are examples of antibody-mediated chronic, progressive autoimmune diseases. Phenotypically dissimilar, MG and RA share common immunological features. However, the immunometabolomic features common to humoral autoimmune diseases remain largely unexplored. OBJECTIVES: The aim of this study was to reveal and illustrate the metabolomic profile overlap found between these two diseases and describe the immunometabolomic significance. METHODS: Metabolic analyses using acid- and dansyl-labelled was performed on serum from adult patients with seropositive MG (n = 46), RA (n = 23) and healthy controls (n = 49) presenting to the University of Alberta Hospital specialty clinics. Chemical isotope labelling liquid chromatography mass spectrometry (CIL LC-MS) methods were utilized to assess the serum metabolome in patients; 12C/13C-dansyl chloride (DnsCl) was used to label amine/phenol metabolites and 12C/13C-p-dimethylaminophenacyl bromide (DmPA) was used for carboxylic acids. Metabolites matching our criteria for significance were selected if they were present in both groups. Multivariate statistical analysis [including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA)] and biochemical pathway analysis was then conducted to gain understanding of the principal pathways involved in antibody-mediated pathogenesis. RESULTS: We found 20 metabolites dysregulated in both MG and RA when compared to healthy controls. Most prominently, observed changes were related to pathways associated with phenylalanine metabolism, tyrosine metabolism, ubiquinone and other terpenoid-quinone biosynthesis, and pyruvate metabolism. CONCLUSION: From these results it is evident that many metabolites are common to humoral disease and exhibit significant immunometabolomic properties. This observation may lead to an enhanced understanding of the metabolic underpinnings common to antibody-mediated autoimmune disease. Further, contextualizing these findings within a larger clinical and systems biology context could provide new insights into the pathogenesis and management of these diseases.
INTRODUCTION:Myasthenia gravis (MG) and rheumatoid arthritis (RA) are examples of antibody-mediated chronic, progressive autoimmune diseases. Phenotypically dissimilar, MG and RA share common immunological features. However, the immunometabolomic features common to humoral autoimmune diseases remain largely unexplored. OBJECTIVES: The aim of this study was to reveal and illustrate the metabolomic profile overlap found between these two diseases and describe the immunometabolomic significance. METHODS: Metabolic analyses using acid- and dansyl-labelled was performed on serum from adult patients with seropositive MG (n = 46), RA (n = 23) and healthy controls (n = 49) presenting to the University of Alberta Hospital specialty clinics. Chemical isotope labelling liquid chromatography mass spectrometry (CIL LC-MS) methods were utilized to assess the serum metabolome in patients; 12C/13C-dansyl chloride (DnsCl) was used to label amine/phenol metabolites and 12C/13C-p-dimethylaminophenacyl bromide (DmPA) was used for carboxylic acids. Metabolites matching our criteria for significance were selected if they were present in both groups. Multivariate statistical analysis [including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA)] and biochemical pathway analysis was then conducted to gain understanding of the principal pathways involved in antibody-mediated pathogenesis. RESULTS: We found 20 metabolites dysregulated in both MG and RA when compared to healthy controls. Most prominently, observed changes were related to pathways associated with phenylalanine metabolism, tyrosine metabolism, ubiquinone and other terpenoid-quinone biosynthesis, and pyruvate metabolism. CONCLUSION: From these results it is evident that many metabolites are common to humoral disease and exhibit significant immunometabolomic properties. This observation may lead to an enhanced understanding of the metabolic underpinnings common to antibody-mediated autoimmune disease. Further, contextualizing these findings within a larger clinical and systems biology context could provide new insights into the pathogenesis and management of these diseases.
Authors: Tatyana D Sotnikova; Jean-Martin Beaulieu; Stefano Espinoza; Bernard Masri; Xiaodong Zhang; Ali Salahpour; Larry S Barak; Marc G Caron; Raul R Gainetdinov Journal: PLoS One Date: 2010-10-18 Impact factor: 3.240
Authors: James T Grist; Lorna B Jarvis; Zoya Georgieva; Sara Thompson; Harpreet Kaur Sandhu; Keith Burling; Ashley Clarke; Sarah Jackson; Mark Wills; Ferdia A Gallagher; Joanne L Jones Journal: J Immunol Date: 2017-12-29 Impact factor: 5.422