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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nevsun Inanc ◽  
Gonca Mumcu ◽  
Meryem Can ◽  
Meral Yay ◽  
Angelika Silbereisen ◽  
...  

AbstractThe 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.

2012 ◽  
Vol 39 (7) ◽  
pp. 1320-1325 ◽  
Author(s):  
LAURINDO FERREIRA da ROCHA ◽  
ÂNGELA LUZIA BRANCO PINTO DUARTE ◽  
ANDRÉA TAVARES DANTAS ◽  
HENRIQUE ATAÍDE MARIZ ◽  
IVAN da ROCHA PITTA ◽  
...  

Objective.To analyze the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA).Methods.IL-22 serum levels were measured in 83 patients with established RA under treatment with disease-modifying antirheumatic drugs and in 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of IL-22 serum levels with disease activity measures [Clinical Disease Activity Index (CDAI) and Disease Activity Score for 28 joints (DAS28)], serological markers, bone erosions, and demographic factors were assessed. Peripheral blood mononuclear cells (PBMC) from 30 patients with RA and 14 controls were purified and stimulatedin vitrowith phorbol myristate acetate (PMA)/ionomycin. IL-22 production by PBMC and in serum was investigated by ELISA.Results.IL-22 levels were increased in patients with RA compared with controls (mean 432.37 pg/ml and 67.45 pg/ml, respectively; p < 0.001). Levels of IL-22 correlated with DAS28 and CDAI measures. Rheumatoid factor (RF) positivity was correlated with higher levels of IL-22 in patients with RA (mean 575.08 pg/ml; p = 0.001). The presence of bone erosions was associated with high IL-22 levels (p = 0.0001). PBMC stimulated with PMA/ionomycin expressed higher levels of IL-22 in patients with RA than controls but this was not significant (mean 584.75 pg/ml and 295.57 pg/ml; p = 0.553).Conclusion.IL-22 is elevated in the serum of patients with established RA. Elevated serum IL-22 allows discrimination between patients with different clinical and laboratory measures and indicates the potential of IL-22 as an additional tool for assessment of activity in RA, particularly in patients with RF antibodies and longterm disease. IL-22 is associated with bone-destructive disease.


2021 ◽  
Vol 10 (22) ◽  
pp. 5324
Author(s):  
In Seol Yoo ◽  
Yu-Ran Lee ◽  
Seong Wook Kang ◽  
Jinhyun Kim ◽  
Hee-Kyoung Joo ◽  
...  

There is growing evidence that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) regulates inflammatory responses. Rheumatoid arthritis (RA) is an autoimmune disease, which is characterized with synovitis and joint destruction. Therefore, this study was planned to investigate the relationship between APE1/Ref-1 and RA. Serum and synovial fluid (SF) were collected from 46 patients with RA, 45 patients with osteoarthritis (OA), and 30 healthy control (HC) patients. The concentration of APE1/Ref-1 in serum or SF was measured using the sandwich enzyme-linked immunosorbent assay (ELISA). The disease activity in RA patients was measured using the 28-joint disease activity score (DAS28). The serum APE1/Ref-1 levels in RA patients were significantly increased compared to HC and OA patients (0.44 ± 0.39 ng/mL for RA group vs. 0.19 ± 0.14 ng/mL for HC group, p < 0.05 and vs. 0.19 ± 0.11 ng/mL for OA group, p < 0.05). Likewise, the APE1/Ref-1 levels of SF in RA patients were also significantly increased compared to OA patients (0.68 ± 0.30 ng/mL for RA group vs. 0.31 ± 0.12 ng/mL for OA group, p < 0.001). The APE1/Ref-1 concentration in SF of RA patients was positively correlated with DAS28. Thus, APE1/Ref-1 may reflect the joint inflammation and be associated with disease activity in RA.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1442.2-1443
Author(s):  
E. Aleksandrova ◽  
A. Novikov ◽  
E. Luchikhina ◽  
D. Karateev ◽  
G. Lukina

Background:YKL-40 (chitinase-3-like 1 protein, human cartilage glycoprotein 39) is one of the major proteins secreted locally in the arthritic joint by activated macrophages, chondrocytes, synoviocytes and neutrophils, YKL-40 an important marker for inflammation, cartilage remodelling and synovial hyperplasia is recognized as a possible auto-antigen in rheumatoid arthritis (RA).Objectives:The aims of the study were to determine the serum level of YKL-40 in early RA and investigate his relationship with biomarkers of disease activity and joint destruction.Methods:We studied 22 patients with early RA (ACR/EULAR 2010 classification criteria); 4 males, 18 females; median and interquartile range (25th—75th percentile) of age 55,0 (43,0-64,0) years, disease duration 7,0 (5,0-11,0) months, DAS28 4,9 (4,3-5,8); 86% IgM rheumatoid factor (IgM RF) +; 91% anti-cyclic citrullinated peptide antibody (anti-CCP) +. All patients were treated with methotrexate (MTX). Three (14 %) patients received low oral doses of steroids and intra-articular injections. The control group included 22 healthy donors (HC). Radiographs were scored according to the van der Heijde-modified Sharp score. YKL-40, matrix metalloproteinase-3 (MMP-3), anti-CCP were detected using commercially available enzyme-linked immunosorbent assays (ELISA). The serum levels of IgM RF, C-reactive protein (CRP), serum amyloid A (SAA) were measured by immunonephelometry.Results:RA patients had significantly higher serum level of YKL-40 than HC (92,1; 68,5-153,1 pg/ml vs 54,0; 41,7-83,2 pg/ml, p<0.01). Serum YKL-40 concentration was positively correlated with DAS 28 (r=0,5; p<0,05), erythrocyte sedimentation rate (ESR) (r=0,5; p<0,05), CRP (r=0,8; p<0,05), SAA (r=0,6; p<0,05) and MMP-3 (r = 0,6; p<0,05). We found no relationship between the level of YKL-40 and articular radiographic changes.Conclusion:Elevated serum concentration of YKL-40 in early RA is associated with clinical and laboratory indicators of disease inflammatory activity and increased level of MMP-3 - an immunological marker of joint destruction.Disclosure of Interests:Elena Aleksandrova: None declared, Alexander Novikov: None declared, Elena Luchikhina Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Consultant of: Abbvie, Biocad, Sanofi, Celgene, Dmitriy Karateev Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Lilly, Bayer, Paid instructor for: Abbvie, Pfizer, Biocad, Sanofi, Novartis, Lilly, Galina Lukina Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Paid instructor for: Abbvie, Biocad, Sanofi, Celgene


2017 ◽  
Vol 24 (8) ◽  
Author(s):  
Anouk van Hooij ◽  
Debbie M. Boeters ◽  
Elisa M. Tjon Kon Fat ◽  
Susan J. F. van den Eeden ◽  
Paul L. A. M. Corstjens ◽  
...  

ABSTRACT Although rheumatoid arthritis (RA) is a chronic, persistent autoimmune disease, 10 to 15% of RA patients achieve sustained disease-modifying antirheumatic drug (DMARD)-free remission over time. The biological mechanisms underlying the resolution of persistent inflammation in RA are still unidentified, and there is a lack of prognostic markers. It is well established that increased serum levels of gamma interferon-induced protein 10 (IP-10) are associated with (acute) increased inflammatory responses (e.g., in leprosy). In order to assess the potential of IP-10 as a diagnostic tool for inflammatory episodes of RA, we performed a retrospective study and assessed IP-10 levels in longitudinally banked serum samples obtained from patients upon first diagnosis of RA. The selection consisted of 15 persistent RA patients and 19 patients who achieved DMARD-free sustained remission. IP-10 levels, measured by use of a user-friendly quantitative lateral flow assay (LFA), showed up to 170-fold variation interindividually, and baseline IP-10 levels could not be differentiated between the two patient groups. However, a difference in the change in IP-10 levels between the first and last visits (ΔIP-10) was observed (P = 0.003) between DMARD-free (median ΔIP-10, −662 pg/ml [decrease]) and persistent (median ΔIP-10, 468 pg/ml [increase]) RA patients. Moreover, intraindividual changes in IP-10 levels during the course of disease corresponded to the disease activity score (DAS) (P = 0.05). These data indicate that IP-10 is associated with disease activity and perseverance of RA. The association of IP-10 with DAS indicates that this tool may be a practical diagnostic aid to help in monitoring disease progression in RA patients and may also find applications in other chronic diseases with exacerbated inflammatory episodes.


2018 ◽  
Vol 12 (1) ◽  
pp. 189-196
Author(s):  
Noha Abdelsalam ◽  
Ashraf Hussein Mohamed ◽  
Sameh Abdellatif ◽  
Eslam Eid ◽  
Ehsan Mohamed Rizk ◽  
...  

Background:Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by destruction of the joint cartilage and bone. Endothelial dysfunction (ED) in RA may be related to disease activity. Our objective is to explore serum levels of endothelial cell-specific molecule-1 (ESM-1) as a biomarker for RA disease activity.Methods:A cross-sectional study was carried out and included 83 adult patients with RA, in addition to 20 healthy subjects (age and sex-matched) as a control group. Based on Disease Activity Score in 28 joints (DAS-28), the patient's group was subdivided into four subgroups(remission, mild, moderate and severe disease activity state). The demographic & clinical data, BMI, DAS-28 and Serological assessment [Erythrocyte Sedimentation Rate (ESR), CRP, Rheumatoid Factor (RF) and Anti-Citrullinated Peptide Antibody (ACPA)] were recorded. ESM-1was assayed for all participants.Results:Serum levels of ESM1 were significantly higher in the patient group than the control group (P< 0.0001). ESM-1 serum levels were significantly higher in patients with severe disease activity subgroup compared with patients with remission and mild disease activity subgroups (P< 0.0001). ESM-1 was positively and significantly correlated with DAS-28 score, The Health Assessment Questionnaire Disability Index (HAQ-DI) and modified Larsen score (P= 0.002, 0.0001 & 0.0001 respectively).Conclusion:ESM-1 could be a biomarker for RA disease activity.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
You-Jung Ha ◽  
Dong Woo Han ◽  
Ji Hyoun Kim ◽  
Sang Wan Chung ◽  
Eun Ha Kang ◽  
...  

Semaphorin 3A (Sema3A) and semaphorin 4D (Sema4D) are molecules which regulate immune responses as well as bone remodeling process. The aim of this study was to evaluate the serum levels of Sema3A and Sema4D and to investigate their clinical significance in rheumatoid arthritis (RA). The serum levels of Sema3A and Sema4D were measured in 130 patients with RA and 65 sex- and age-matched healthy individuals. Circulating levels of biomarkers of RA-related inflammation and bone turnover such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-22, IL-34, osteopontin, Dkk-1, and sclerostin were also measured. Disease activity was determined by the 28-joint disease activity score (DAS28), and radiographic joint damage was assessed by the modified Sharp van der Heijde score (SHS). The serum levels of Sema3A were significantly higher in patients with RA than those in healthy controls (p<0.001), whereas serum4D levels did not differ between the two groups. The levels of Sema4D showed a positive correlation with C-reactive protein (p=0.001) and IL-6 (p<0.001) levels, whereas the levels of Sema3A showed a negative correlation with Dkk-1 (p=0.007) and TNF-α (p=0.001). Even though Sema3A and Sema4D levels were comparable between RA patients with DAS28> 3.2 and with DAS28 ≤ 3.2, RA patients with radiographic progression (ΔSHS change/year ≥ 1) had significantly higher baseline levels of Sema4D than those without progression (p=0.029). Additionally, when RA patients were divided into 3 groups using tertiles of Sema4D levels, the percentage of progressors was significantly increased (p=0.045). In multivariate logistic regression analysis, serum Sema4D levels were an independent risk factor for radiographic progression. Our results suggest that the baseline levels of Sema4D might be a useful marker to identify RA patients with subsequent radiographic progression and that Sema4D may be an active mediator involved in RA-induced joint damage.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 546.2-546
Author(s):  
A. Damiani ◽  
F. Bartoli ◽  
V. Gori ◽  
S. Bellando-Randone ◽  
G. Fiori ◽  
...  

Background:In refractory IJD, remission may be obtained with antiTNFa drugs and other biological disease modifying anti-rheumatic drugs (bDMARDs). The last EULAR recommendations suggest tapering of bDMARD when remission persists1. However, best timing and modality of tapering are uncertain and specific knowledge on patients’ characteristics associated to a better outcome is still lacking.Objectives:To evaluate the persistency of remission after increasing the interval between injections of Golimumab in a group of patients affected by rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and juvenile idiopathic arthritis (JIA) and to identify any variables associated to disease flare after tapering.Methods:Between 2011 and July 2020, 80 patients affected by RA, PsA, AS and JIA treated with Golimumab were enrolled. Their demographic and clinical data, including inflammation (ESR and cRP) and clinimetric indices (DAS28 or BASDAI), were collected at baseline and during the follow up visit (T1). In 22/80 patients that reached clinical remission at T1, the time between Golimumab injections has been prolonged (mean time between injection: 43.7 days); ESR and cRP, DAS28/BASDAI, and time since the start of the tapering (weeks) were evaluated in the next control visit (T2).Results:80 patients were enrolled (32 male, mean age 50.6 years +/- 13.91), 34 AS, 33 PsA, 9 RA and 4 JIA. At baseline they have an active disease with a DAS 28 of 4.74+/-0.85 and a BASDAI of 5.23+/- 1.31. At T1, 60/80 patients were in remission (75%), with a mean DAS 28 of 1.84+/- 0.6 and an average BASDAI of 1.32+/-0.6, and 22/60 patients started drug tapering. At T2, 20/22 patients (91%) were in remission, (DAS 28 1.9+/-0.49, BASDAI of 0.8+/- 0, 67). A significantly higher BASDAI was observed at T1, even though in the range of absence of disease activity (2.2, +/- 0.28 vs 0.58, +/- 0.47; p <0.001) in patients who, after extending the therapeutic interval (T1) were no longer in remission at T2. Patients with a flare of disease activity (2/22) were taken back to the 28 days window of Golimumab with a prompt recovery of disease remission. Out of the 38 patients maintained at the standard dose, 4 experienced a disease flare with necessity to switch or swope bDMARD, with a retention rate in this group of 90%. Difference of retention rate between patients on standard vs reduced dose was not statistically significative.Conclusion:Tapering of Golimumab was successful in 91% of the cases without flare. Moreover, the prolongation of the increase of the treatment window provided the same result as that obtained in patients that continued in the standard time window. This evidence suggests that the extension of the gap between Golimumab administrations may be feasible and safely applied in practice.References:[1]Smolen JS, Landewé RBM, Bijlsma JWJ, et al EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update Annals of the Rheumatic Diseases 2020;79:685-699.Disclosure of Interests:None declared


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