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

Milica Milivojevic, Xiaoyu Che, Lucinda Bateman, Aaron Cheng, Benjamin A. Garcia, Mady Hornig, Manuel Huber, Nancy G. Klimas, Bohyun Lee, Hyoungjoo Lee, Susan Levine, Jose G. Montoya, Daniel L. Peterson, Anthony L. Komaroff, W. Ian Lipkin

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish
Article numbere0236148
JournalPloS one
Issue number7
StatePublished - Jul 2020


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