Impaired periodontitis-induced cytokine production by peripheral blood monocytes and myeloid dendritic cells in patients with rheumatoid arthritis : a case-control study

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Background: Immune cells from rheumatoid arthritis (RA) patients display a reduced in vitro response to Porphyromonas gingivalis (P. gingivalis), which may have functional immune consequences. The aim of this study was to characterize, by flow cytometry, the frequency/activity of monocytes and naturally occurring myeloid dendritic cells (mDCs) in peripheral blood samples from patients with periodontitis and patients with periodontitis and RA. Methods: The relative frequency of monocytes and mDCs in the whole blood, the frequency of these cells producing TNF$\alpha$ or IL-6 and the protein expression levels for each cytokine, before and after stimulation with lipopolysaccharide (LPS) from Escherichia coli plus interferon-$\gamma$ (IFN-$\gamma$), were assessed by flow cytometry, in peripheral blood samples from 10 healthy individuals (HEALTHY), 10 patients with periodontitis (PERIO) and 17 patients with periodontitis and RA (PERIO+RA). Results: The frequency of monocytes and mDCs producing IL-6 or TNF-$\alpha$ and the expression of IL-6 and TNF-$\alpha$ in the PERIO group were generally higher. Within the PERIO+RA group, P. gingivalis and related antibodies were negatively correlated with the monocyte and mDC expression of IL-6. A subgroup of the PERIO+RA patients that displayed statistically significantly lower frequencies of monocytes producing IL-6 after activation presented statistically significantly higher peptidylarginine deiminase (PAD)2/4 activity, anti-arg-gingipain (RgpB) IgG levels, mean probing depth (PD), periodontal inflamed surface area (PISA) and bleeding on probing (BoP). Conclusions: In the patients with PERIO+RA, innate immune cells seemed to produce lower amounts of pro-inflammatory cytokines, which are correlated with worse periodontitis-related clinical and microbiological parameters.