Elevated serum TREM-1 is associated with periodontitis and disease activity in rheumatoid arthritis

Abstract

The triggering receptor expressed on myeloid cells 1 (TREM-1) and peptidoglycan recognition protein 1 (PGLYRP1) are involved in the propagation of inflammatory responses. This study investigated whether serum levels of TREM-1 and PGLYRP1 correlate with periodontitis in rheumatoid arthritis (RA) patients. A total of 154 non-smoking participants with RA (n = 55, F/M: 41/14), Behçet´s disease (BD, n = 41, F/M: 30/11) and healthy controls (HC, n = 58, F/M: 40/18) were recruited. Serum and saliva were collected, the 28-joint disease activity score (DAS-28) was calculated and dental/periodontal measurements were recorded. Serum TREM-1 and PGLYRP1 levels were measured by ELISA and salivary bacterial DNA counts by quantitative polymerase chain reaction. TREM-1 and PGLYRP1 levels were higher in RA (166.3 ± 94.3; 155.5 ± 226.9 pg/ml) than BD (102.3 ± 42.8; 52.5 ± 26.3 pg/ml) and HCs (89.8 ± 55.7; 67.4 ± 37.3 pg/ml) (p < 0.05). In RA, periodontitis was associated with increased TREM-1 and PGLYRP1 levels (p < 0.05), yet in patients under methotrexate TREM-1 levels were lower. TREM-1 correlated with C-reactive protein (CRP) levels, DAS-28 and erythrocyte sedimentation rate, whereas PGLYRP1 positively correlated with CRP. RA patients displayed 3.5-fold higher salivary bacterial DNA counts than HCs. Increased serum TREM-1 levels correlated with PGLYRP1, CRP and DAS-28-ESR in RA patients with periodontitis.

Figure 1

Comparisons among the three groups. (A) total bacterial DNA counts in saliva are compared between pair of groups (Mann–Whitney, p = 0.05). (B) serum TREM-1 levels are compared between pair of groups (Mann–Whitney, p = 0.05). (C) serum PGLYRP1 levels are compared between pair of groups (Mann–Whitney, p = 0.05). Boxplots show the first and third quartile (top and bottom edges of the rectangle) divided by the median. Whiskers correspond to the highest and lowest values. A base-10 log scale is applied on the y-axis. ***p ≤ 0.001, ****p ≤ 0.0001. RA rheumatoid arthritis, BD Behçet’s disease, HC healthy control.

Figure 2

TREM-1 and PGLYRP1 serum levels in RA patients. (A) serum levels of TREM-1 and PGLYRP1 are compared between RA patients with and without MTX in their therapeutic regimen. (B) serum levels of TREM-1 and PGLYRP1 are compared between RA patients affected or not by periodontitis. (C) and (D) serum levels of TREM-1 and PGLYRP1 are compared between subgroups of RA patients clustered based on MTX use and presence of periodontitis. Boxplots show the first and third quartile (top and bottom edges of the rectangle) divided by the median. Whiskers correspond to the highest and lowest values. A base-10 log scale is applied on the y-axis. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001. MTX methotrexate, ns non-significant.

Figure 3

Scheme of the mediation analysis that illustrates the direct effect of “periodontitis” as independent variable on the dependent variable “TREM-1”, as well as the indirect effect of “PGLYRP1” as the mediator variable.