scholarly journals Levels of the Novel Endogenous Antagonist of Ghrelin Receptor, Liver-Enriched Antimicrobial Peptide-2, in Patients with Rheumatoid Arthritis

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1006
Author(s):  
Vera Francisco ◽  
Sulay Tovar ◽  
Javier Conde ◽  
Jesús Pino ◽  
Antonio Mera ◽  
...  

Rheumatoid arthritis (RA) is a debilitating, chronic, inflammatory, autoimmune disease associated with cachexia. The substitutive therapy of gut hormone ghrelin has been pointed at as a potential countermeasure for the management of metabolic and inflammatory complications in RA. The recent discovery of liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous inverse agonist/antagonist of the ghrelin receptor makes feasible the development of a more rational pharmacological approach. This work aimed to assess the serum LEAP2 levels, in a cohort of RA patients, in comparison with healthy individuals and determine its correlation with inflammatory parameters. LEAP2 levels were determined by a commercial ELISA kit, plasma C-reactive protein (CRP) levels were evaluated using immunoturbidimetry, and serum levels of inflammatory mediators, namely IL-6, IL-8, IL-1β, MIP1α, MCP1, and LCN2, were measured by XMap multiplex assay. LEAP2 serum levels were significantly increased in RA patients (n = 101) compared with control subjects (n = 26). Furthermore, the LEAP2 levels significantly correlated with CRP and inflammatory cytokines, but not with BMI. These data reveal LEAP2 as a new potential RA biomarker and indicated the pharmacological control of LEAP2 levels as a novel approach for the treatment of diseases with alterations on the ghrelin levels, such as rheumatoid cachexia.

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Khadiga Ahmed Ismail

Background: Tumor necrosis Factor-α (TNF-α) is encoded and controlled by TNF-α gene, which is involved in rheumatoid arthritis (RA) susceptibility. This research aimed to identify genetic variations of TNF-α (G308A) and to establish its association with inflammatory markers in Rheumatoid Arthritis predisposition. Methods: In the present study, fifty RA patients and fifty volunteers were involved and evaluated for the C-reactive protein, rheumatoid factor, and TNF-α were estimated by ELISA, Erythrocyte Sedimentation Rate (ESR) by Wintergreen method and for TNF-α-308 G>A polymorphism by polymerase chain reaction with amplification refractory mutation system (PCR-ARMS). Results: The CRP, RF, ESR and TNF-α were significantly elevated in RA patients relative to controls. The serum level TNF-α was also significantly elevated in female patients and in patients ≥50 years. Analysis of TNF-308 gene polymorphism revealed that GG genotypes were more prevalent in RA patients than in the healthy individuals and that GG genotype may be a potential factor to RA. The G allele was more common in RA than in the control. Elevated TNF-α serum levels were significantly associated the GG genotype and functional disability in RA patients. Conclusion: TNF-α promoter 308polymorphism GG genotype may be considered as a risk factor for RA and the TNF-α serum level was significantly related to the functional disability in the disease.


2011 ◽  
Vol 50 (4) ◽  
pp. 269-275 ◽  
Author(s):  
Takumi Yoshino ◽  
Natsuko Kusunoki ◽  
Nahoko Tanaka ◽  
Kaichi Kaneko ◽  
Yoshie Kusunoki ◽  
...  

2009 ◽  
Vol 26 (3) ◽  
pp. 119-126 ◽  
Author(s):  
Rosa Elena Navarro-Hernández ◽  
Edith Oregon-Romero ◽  
Mónica Vázquez-Del Mercado ◽  
Héctor Rangel-Villalobos ◽  
Claudia Azucena Palafox-Sánchez ◽  
...  

To investigate the association of sICAM-1 and sVCAM-1 with ICAM1 721G>A and VCAM1 1238G>C polymorphisms and rheumatoid arthritis (RA) clinical activity, sixty RA patients and 60 healthy non-related subjects (HS) matched for age and sex were recruited. Soluble adhesion molecules were determined by ELISA technique. Rheumatoid factor (RF), C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were measured by routine methods. Disability and clinical activity was measured with Spanish-HAQ-DI and DAS28 scores, respectively. The ICAM1 and VCAM1 polymorphism were identified using the PCR-RFLP procedure. Inter-group comparison showed increased levels of sICAM-1 and sVCAM-1 in RA patients (284 and 481 ng/mL) versus HS (132 and 280 ng/mL); in the RA group, significant correlations between sVCAM-1 and RF (r= 0.402), ESR (r= 0.426), Spanish-HAQ-DI (r= 0.276), and DAS28 (r= 0.342) were found, whereas sICAM-1 only correlated with RF (r= 0.445). In RA patients, a significant association with the 721A allele of ICAM1 polymorphism (p= 0.04), was found. In addition, the allele impact (G/A+A/A) of this polymorphism was confirmed, (p= 0.038, OR = 2.3, C.I. 1.1–5.0). sVCAM-1 and sICAM-1 serum levels reflected the clinical status in RA, independently of the ICAM1 and VCAM1 polymorphism. However, the ICAM1 721A allele could be a genetic marker to RA susceptibility.


2018 ◽  
Vol 31 (3) ◽  
pp. 55
Author(s):  
Nashwa S. Sultan ◽  
Anwar F. AL- Tai

Rheumatoid arthritis is a chronic inflammatory autoimmune disease its etiology is  unknown . The classical autoimmune diseases, have adaptive immune genetic associations with autoantibodies and major histocompatibility complex(MHC) class II such as rheumatoid arthritis (RA), diabetes mellitus type two (DM II). Serum of99 males suffering from RA without DMII as group (G1), 45 males suffering from RA with DM II as group (G2) and 40 healthy males as group (G3) were enrolled in this study to estimation of alkaline phosphates (ALP),C-reactive protein(CRP) and Pentraxin-3(PTX). Results showed a highly significant increase in PTX3 levels in G1 and G2 compared to G3 and a significant decrease in G1comparing to G2. Results also revealed a significant increase in CRP levels in G1 and G2 when compared to G3 , as well as a significant increase in G2 comparing to G1. Results showed a significant decrease in ALP levels in G1 and G2 while this phrase must no differences was observed betweenG1 and G2and there was no significant positive correlation  between PTX3 and ALP in sera of RA males patients with and without DM II it be showed in our study.


2019 ◽  
Vol 57 (3) ◽  
pp. 274-279 ◽  
Author(s):  
A. S. Avdeeva ◽  
A. M. Satybaldyev ◽  
N. V. Demidova ◽  
N. Yu. Nikishina ◽  
E. V. Gerasimova ◽  
...  

Objective:to analyze therapy with rituximab (RTM) in real clinical practice according to the data available in OREL registry of patients with active rheumatoid arthritis (RA).Subjects and methods. The analysis included 349 patients. All the patients received RTM: 340 – the original drug (MabThera®) and 9 – the biosimilar Acellbia®. 263 patients (75.4%) received RTM in combination with disease-modifying anti-rheumatic drugs (DMARDs) and 86 (24.6%) – RTM as monotherapy.Results and discussion. Of the 349 patients included in the analysis, 272 (77.9%) patients received RTM as the first biologic agent (BA) (263 patients were treated with the original drug and 9 – with the biosimilar) and 77 (22.1%) patients had previously used the BA. The majority of patients (n=205 (58.7%)) received three or more; 109 (31.2%) patients – one, and 35 (10%) – two RTM courses of RTM therapy. RTM caused a significant reduction in disease activity just after the first therapy course and in the levels of acute-phase reactants (C-reactive protein (CRP) and ESR); after the fifth therapy course, median CRP concentration decreased by 1.4 times and amounted to 7 [1.2; 17.9] mg/l and that of ESR reduced by 1.8 times and was 10 [5; 20] mm/hr (p<0.05).Conclusion.The analysis of RTM therapy in RA patients in real clinical practice demonstrated that in most cases RTM was given as the first BA, in combination with DMARDs, the main agent of which was methotrexate. The use of RTM was accompanied by a significant reduction in disease activity and in the serum levels of acute-phase reactants and autoantibodies.


2019 ◽  
Vol 20 (16) ◽  
pp. 4046 ◽  
Author(s):  
Valerie R. Wiersma ◽  
Alex Clarke ◽  
Simon D. Pouwels ◽  
Elizabeth Perry ◽  
Trefa M. Abdullah ◽  
...  

The aetiology of rheumatoid arthritis (RA) is unknown, but citrullination of proteins is thought to be an initiating event. In addition, it is increasingly evident that the lung can be a potential site for the generation of autoimmune triggers before the development of joint disease. Here, we identified that serum levels of galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, are elevated in RA patients, and are even further increased in patients with comorbid bronchiectasis, a lung disease caused by chronic inflammation. The serum concentrations of Gal-9 correlate with C-reactive protein levels and DAS-28 score. Gal-9 activated polymorphonuclear leukocytes (granulocytes) in vitro, which was characterized by increased cytokine secretion, migration, and survival. Further, granulocytes treated with Gal-9 upregulated expression of peptidyl arginine deiminase 4 (PAD-4), a key enzyme required for RA-associated citrullination of proteins. Correspondingly, treatment with Gal-9 triggered citrullination of intracellular granulocyte proteins that are known contributors to RA pathogenesis (i.e., myeloperoxidase, alpha-enolase, MMP-9, lactoferrin). In conclusion, this study identifies for the first time an immunomodulatory protein, Gal-9, that triggers activation of granulocytes leading to increased PAD-4 expression and generation of citrullinated autoantigens. This pathway may represent a potentially important mechanism for development of RA.


Author(s):  
Vladimir D. Nazarov ◽  
Sergey V. Lapin ◽  
Ksenia V. Tulenko ◽  
Rusana R. Samigullina ◽  
Vadim I. Mazurov

Purpose. The study assesses the impact of tocilizumab immunogenicity markers on clinical response to conducted treatment in patients with rheumatoid arthritis. Materials and methods. A total of 17 patients with the confirmed diagnosis of RA receiving tocilizumab therapy for more than 1 year were enrolled into the study. Blood serum samples were collected once every six months before every drug injection during 2.5 years of treatment. The concentration of antibodies to tocilizumab and level of tocilizumab was determined using the ELISA. Additionally, DAS28 values were measured at the first and the last patient visit during the course of study, whereas levels of C-reactive protein (CRP), white blood cells, platelets, rheumatoid factor, and circulating immune complexes were only measured at the last examination. Results. Positive correlations between the antibodies to tocilizumab and the last point DAS28 values were found, as well as a negative correlation of tocilizumab level and the level of DAS28. Conclusions. The data obtained indicate a significant effect of serum levels of tocilizumab, as well as of the concentration of antibodies to tocilizumab on the effectiveness of RA treatment. A routine study of these biomarkers might be useful for individualizing treatment approaches for RA patients and determining the causes of tocilizumab resistance.


2014 ◽  
pp. 475-481 ◽  
Author(s):  
O. SGLUNDA ◽  
H. F. MANN ◽  
H. HULEJOVÁ ◽  
O. PECHA ◽  
L. PLEŠTILOVÁ ◽  
...  

Interleukin-21 (IL-21) plays an important role in the pathogenesis of rheumatoid arthritis (RA). The aim of our study was to assess serum levels of IL-21 in patients with recent-onset RA in relation to disease activity and response to treatment. We analyzed serum levels of IL-21 in 51 RA patients, both before and 12 weeks after the initiation of treatment and in 36 healthy individuals. Disease activity was assessed at baseline and at weeks 12 and 24 using the Disease Activity Score for 28 joints, serum levels of C-reactive protein, and the total swollen joint count. We found that IL-21 levels were not increased in patients with recent-onset RA compared with healthy controls, but they had significantly decreased from baseline to week 12 during treatment. Baseline levels of IL-21 significantly correlated with measures of disease activity (p<0.02 for all). Although IL-21 levels did not predict achievement of remission, decrease in IL-21 levels correlated with improvement in disease activity after 12 weeks (p<0.02) and also after 24 weeks (p<0.04) of treatment. Our data suggest that circulating IL-21 levels may serve as a biomarker of disease activity and better outcome in early phase of RA.


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.


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