1. Plasma proteomic profiling suggests an association between antigen driven clonal B cell expansion and ME/CFS.
- Author
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Milivojevic, Milica, Che, Xiaoyu, Bateman, Lucinda, Cheng, Aaron, Garcia, Benjamin A., Hornig, Mady, Huber, Manuel, Klimas, Nancy G., Lee, Bohyun, Lee, Hyoungjoo, Levine, Susan, Montoya, Jose G., Peterson, Daniel L., Komaroff, Anthony L., and Lipkin, W. Ian
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CLONE cells ,LIQUID chromatography-mass spectrometry ,B cells ,VISCERAL pain ,IRRITABLE colon ,ORTHOSTATIC intolerance - Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an unexplained chronic, debilitating illness characterized by fatigue, sleep disturbances, cognitive dysfunction, orthostatic intolerance and gastrointestinal problems. Using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we analyzed the plasma proteomes of 39 ME/CFS patients and 41 healthy controls. Logistic regression models, with both linear and quadratic terms of the protein levels as independent variables, revealed a significant association between ME/CFS and the immunoglobulin heavy variable (IGHV) region 3-23/30. Stratifying the ME/CFS group based on self-reported irritable bowel syndrome (sr-IBS) status revealed a significant quadratic effect of immunoglobulin lambda constant region 7 on its association with ME/CFS with sr-IBS whilst IGHV3-23/30 and immunoglobulin kappa variable region 3–11 were significantly associated with ME/CFS without sr-IBS. In addition, we were able to predict ME/CFS status with a high degree of accuracy (AUC = 0.774–0.838) using a panel of proteins selected by 3 different machine learning algorithms: Lasso, Random Forests, and XGBoost. These algorithms also identified proteomic profiles that predicted the status of ME/CFS patients with sr-IBS (AUC = 0.806–0.846) and ME/CFS without sr-IBS (AUC = 0.754–0.780). Our findings are consistent with a significant association of ME/CFS with immune dysregulation and highlight the potential use of the plasma proteome as a source of biomarkers for disease. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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