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Single-cell Transcriptomic Analysis of Systemic Autoinflammatory Diseases with Anti-TNFα Therapy

Systemic autoinflammatory diseases (SAIDs) are a group of rare diseases characterized by recurrent or continuous inflammation, typically accompanied by genetic variants. Good responses to anti-TNFα therapy were observed in SAIDs patients. However, the mechanisms underlying the disease flare and the response to TNFα blocking therapy have not been fully elucidated. Here, we use single-cell RNA sequencing technology to describe the transcriptomic profile of PBMCs and PMNs in SAIDs patients both before and after anti-TNFα treatment. We found that interferon responses are involved in the active phase of the disease. After anti-TNFα therapy, we observed remission from clinical symptoms while unexpected elevation of TNFα and IL-1, indicating that these inflammatory cytokines are not positively correlated with disease activity. Trajectory analysis showed that inhibition of macrophage differentiation, rather than reduction of the inflammatory cytokines, as the potential mechanism of anti-TNFα treatment response in SAIDs.