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.

中文翻译：

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原型自身免疫性体液疾病的代谢组学特征重叠：重症肌无力和类风湿关节炎的比较。

引言重症肌无力（MG）和类风湿关节炎（RA）是抗体介导的慢性进行性自身免疫疾病的实例。从表型上看，MG和RA具有共同的免疫学特征。然而，体液自身免疫疾病共有的免疫代谢特征仍未得到充分开发。目的本研究的目的是揭示和说明这两种疾病之间的代谢组学特征重叠，并描述其免疫代谢学意义。方法对呈递给阿尔伯塔大学医院专科门诊的血清阳性MG（n = 46），RA（n = 23）和健康对照组（n = 49）的成年患者血清进行酸和丹磺酰基标记的代谢物分析。化学同位素标记液相色谱质谱法（CIL LC-MS）用于评估患者的血清代谢组。使用12C / 13C-丹磺酰氯（DnsCl）标记胺/酚代谢物，使用12C / 13C-对-二甲基氨基苯甲酰溴（DmPA）制备羧酸。如果两组中都存在符合我们显着性标准的代谢物，则应进行选择。然后进行多变量统计分析[包括主成分分析（PCA）和偏最小二乘判别分析（PLS-DA）]和生化途径分析，以了解与抗体介导的发病机制有关的主要途径。结果与健康对照组相比，我们发现20种代谢物在MG和RA中均失调。最突出的是 观察到的变化与苯丙氨酸代谢，酪氨酸代谢，泛醌和其他萜类醌生物合成以及丙酮酸代谢相关的途径有关。结论从这些结果可以明显看出，许多代谢物是体液性疾病常见的，并表现出显着的免疫代谢性质。该观察结果可以导致对抗体介导的自身免疫病常见的代谢基础的理解得到增强。此外，在较大的临床和系统生物学背景下将这些发现进行背景研究可以为这些疾病的发病机理和治疗提供新的见解。结论从这些结果可以明显看出，许多代谢物是体液性疾病常见的，并表现出显着的免疫代谢性质。该观察结果可以导致对抗体介导的自身免疫病常见的代谢基础的理解得到增强。此外，在较大的临床和系统生物学背景下将这些发现进行背景研究可以为这些疾病的发病机理和治疗提供新的见解。结论从这些结果可以明显看出，许多代谢物是体液性疾病常见的，并表现出显着的免疫代谢性质。该观察结果可以导致对抗体介导的自身免疫病常见的代谢基础的理解得到增强。此外，在较大的临床和系统生物学背景下将这些发现进行背景研究可以为这些疾病的发病机理和治疗提供新的见解。