A new score based on the combination of serum cytokine levels and blood parameters could be a promising indicator of bacterial infections in patients with rheumatoid arthritis (RA), according to study results published in Cytokine.

Patients with RA are more susceptible to infections, which were reported to be a primary cause of death in this population. In many cases it is challenging to discriminate between bacterial infections and RA flare, as both have similar clinical manifestations. In the current study, the aim was to assess the ability of various cytokines and blood parameters to differentiate between the 2 entities.

The retrospective study included data from 168 patients (118 women, mean age, 55.3 years) with RA, including with 76 patients with bacterial infections and 92 patients with RA flare. The levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were collected for all patients and for 81 age- and sex-matched healthy controls. Bacterial infection was confirmed by clinical symptoms, imaging, microbial culture, and antibiotic response.

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The receiver operating characteristics (ROC) curves analysis was used to determine the discriminative ability of the panel of serum cytokine and blood parameters. A bioscore system was generated based on the cut-off value.

The serum levels of IL-6 (P =.006), IL-10 (P =.019), IFN-γ (P =.033), C-reactive protein (CRP) (P <.001), and erythrocyte sedimentation rate (ESR) (P <.001) were higher in patients with bacterial infection, compared with patients with RA flare. On the other hand, levels of CD19+ B cells (P <.001) and CD4+ T cells (P =.009) were lower.

ROC curve analysis revealed that for discriminating bacterial infection, the area under the curve of the combination of IL-6, IL-10, IFN-γ, ESR, CRP, CD19+ B cells, and CD4+ T cells  was 0.827 (95% CI, 0.760-0.881; P <.001), with a sensitivity of 65.75% and specificity of 88.04%. This combination was better than individual indicators for diagnosis of infection in patients with RA.

The bioscore system included 7 biomarkers: IL-6, IL-10, IFN-γ, ESR, CRP, CD19+ B cells and CD4+ T cells. Each of these biomarkers was graded (0 and 1) according to their cut-off values. Bacterial infections were reported in all 7 (100%) patients with a score of 7, compared to none of the patients with a bioscore of 0.

The researchers noted that high infection prevalence could have affected the negative predictive value of the bioscore and called for additional studies to confirm the findings.

“[O]ur findings suggest that serum cytokine levels are promising biomarkers of bacterial infection in RA. Additionally, our data support that the combination of ESR, CRP, IL-6, IL-10 IFN-γ, CD19+ B cells and CD4+ T cells may provide a valuable tool to distinguish between bacterial infections and RA flare,” concluded the researchers.


Qin Y, Feng M, Wu Y, et al. Comprehensive analysis of multiple cytokines and blood parameters for the diagnosis of bacterial infections in rheumatoid arthritis. Cytokine. Published online Aug 19, 2020. doi:10.1016/j.cyto.2020.155251