Plasma proteomic profiling suggests an association between antigen driven clonal B cell expansion and ME/CFS

• Published in: PloS one Vol. 15; no. 7; p. e0236148
• Main Authors: 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, Lipkin, W. Ian
• Format: Journal Article
• Language: English
• Published: San Francisco, CA USA Public Library of Science 21.07.2020; Public Library of Science (PLoS)
• Subjects: Antigens; B cells; Biology and Life Sciences; Health aspects; Medicine and Health Sciences; Methods; Proteomics; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0236148

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.