Skewing of the B cell receptor repertoire in myalgic encephalomyelitis/ chronic fatigue syndrome, by Wakiro Sato, Hirohiko Ono, Takaji Matsutani, Masakazu Nakamura, Isu Shin, Keiko Amano, Ryuji Suzuki, Takashi Yamamura in Brain, Behavior, and Immunity, Vol 95, July 2021, Pages 245-255
Highlights
- ME/CFS is characterized by skewed B cell receptor gene usage.
- Upregulation of specific IGHV genes correlated to infection-related episodes at onset.
- Plasmablasts of ME/CFS patients upregulated interferon response genes.
- B cell receptor repertoire analysis can provide a useful diagnostic marker in ME/CFS.
Research abstract:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition characterized by fatigue and post-exertional malaise, accompanied by various signs of neurological and autonomic dysfunction. ME/CFS is often triggered by an infectious episode and associated with an aberrant immune system.
Structure of the B cell receptor
Here we report that ME/CFS is a disorder characterized by skewed B cell receptor gene usage. By applying a next-generation sequencing to determine the clone-based IGHV/IGHD/IGHJ repertoires, we revealed a biased usage of several IGHV genes in peripheral blood B cells from ME/CFS patients. Results of receiver operating characteristic (ROC) analysis further indicated a possibility of distinguishing patients from healthy controls, based on the skewed B cell repertoire.
Meanwhile, B cell clones using IGHV3-30 and IGHV3-30-3 genes were more frequent in patients with an obvious infection-related episode at onset, and correlated to expression levels of interferon response genes in plasmablasts.
Collectively, these results imply that B cell responses in ME/CFS are directed against an infectious agents or priming antigens induced before disease onset.
From the Discussion:
In conclusion, we demonstrated that specific BCR IGH usage is selectively upregulated in ME/CFS patients compared with HCs. Among the upregulated genes, IGHV3-30/3-30-3 are associated with an infection-related episode before disease onset, with relatively short disease duration and with the expression of type 1 IFN response genes in PB. BCR repertoire analysis could be developed as a powerful tool to help diagnose ME/CFS. It may also be used to predict the efficacy of B cell-targeted therapy, which is effective in a subgroup of patients.
