Background/Purpose: Tocilizumab (TCZ), an anti-IL-6 receptor antibody, has been shown to be effective in the treatment of adult-onset Still’s disease (AOSD), a systemic inflammatory disease. However, under treatment with TCZ, CRP becomes negative regardless of disease activity, making it difficult to use it as an inflammation marker. Therefore, this study aimed to construct AOSD disease activity indices independent of TCZ administration based on the results of RNA-seq analysis.

Methods: Peripheral blood RNA-seq was performed in AOSD patients and healthy controls (HCs). Genes differentially expressed in AOSD (AOSD-DEGs) were extracted from a comparative analysis between high disease activity patients and training HCs. A partial least squares regression model was constructed using AOSD-DEG expression level as an explanatory variable and high disease activity (1) and HC (0) as objective variables. The output of the model was defined as the AOSD gene scores, and the scores of the validation cohort (validation HCs, patients achieving clinical remission; remission AOSD, and patients not in clinical remission; non-remission AOSD) were evaluated.

Results: The constructed AOSD gene score could distinguish patients with high disease activity from training HC when the threshold was set at 0.5. In addition, it was also possible to distinguish validation HCs with 100% accuracy. Furthermore, the scores of non-remission AOSD were significantly higher than those of remission AOSD (p < 0.05), regardless of TCZ administration (p < 0.05).

Conclusion: Our findings suggest the possibility of evaluating AOSD disease activity using AOSD gene scores constructed with AOSD-DEGs even when CRP has turned negative due to TCZ administration.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/development-and-evaluation-of-the-adult-onset-stills-disease-activity-index-based-on-whole-rna-seq-analysis-a-novel-approach-independent-of-tocilizumab-treatment/