Diurnal variation of connective tissue metabolites in early and long-standing rheumatoid arthritis and in healthy individuals

2011 ◽  
Vol 40 (2) ◽  
pp. 88-94 ◽  
Author(s):  
T Lottenburger ◽  
P Junker ◽  
K Hørslev-Petersen
2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 906-907
Author(s):  
R. Jiaqi ◽  
J. Zhao ◽  
L. Sun ◽  
Z. MA ◽  
X. Wang

Background:Many autoantibodies are found in the serum of rheumatoid arthritis (RA) patients, including RF, ACPA and so on, which are essential for the disease diagnosis and prognosis judgment. However, 20-30% of patients are still seronegative, so more investigations are needed to find new biomarkers in RA.Objectives:To investigate the prevalence of serum connective tissue growth factor (CTGF) and the association with the clinical features in RA patients.Methods:Serum samples were obtained from 180 patients with RA, 168 patients with other rheumatic diseases, including 43 systemic lupus erythematosus (SLE), 34 osteoarthritis (OA), 17 primary Sjögren’s syndrome (pSS), 20 ankylosing spondylitis (AS), 23 psoriatic arthritis (PsA), 6 reactive arthritis (ReA), 20 systemic sclerosis (SSc), and 5 systemic vasculitis (SV), and 64 healthy individuals in Peking University Third Hospital. The clinical and laboratory data of patients with RA were collected. Levels of CTGF in serum were measured by ELISA. The cut-off value of CTGF was determined by 95 percent of the concentration of the healthy controls. Statistical analyses were performed using the SPSS 24.0 software. Associations between CTGF and the clinical features of RA were evaluated.Results:The prevalence of serum CTGF among RA patients (33.89%) was significantly higher than those of SLE (9.3%), OA (0%), AS (0%), pSS (0%), PsA (0%), ReA (0%), SSc(5%), SV(0%) and healthy controls (4.69%) (p<0.0001). The mean titer of serum CTGF in RA was also significantly higher than those in other rheumatic diseases and healthy controls (p<0.001). At the cutoff value of 264.30 pg/ml, the sensitivity, specificity, positive predictive value and negative predictive value of serum CTGF for RA were 33.89%, 96.55%, 88.41% and 55.45% respectively. Anti-cyclic citrullinated peptide (CCP) antibody (p<0.001), rheumatoid factor (p<0.001), IgG (p=0.025) and IgM (p=0.004) in CTGF-positive patients were higher than those in CTGF-negative patients. Besides, more patients with interstitial lung disease (ILD) were found in CTGF-positive RA.Conclusion:Serum CTGF, as a novel biomarker, has certain diagnostic value for RA. Further studies are necessary to get more knowledge for the diagnostic performance of CTGF in RA.References:[1] Ramazani Y, et al. (2018) Connective tissue growth factor (CTGF) from basics to clinics. Matrix Biol 68-69:44-66.[2] Nozawa K, F et al. (2009) Connective tissue growth factor promotes articular damage by increased osteoclastogenesis in patients with rheumatoid arthritis. Arthritis research & therapy 11 (6):R174.[3] Yang X, et al. (2017) Serum connective tissue growth factor is a highly discriminatory biomarker for the diagnosis of rheumatoid arthritis. Arthritis research & therapy 19 (1):257.[4] Wei JL, et al. (2018) Role of ADAMTS-12 in Protecting Against Inflammatory Arthritis in Mice By Interacting With and Inactivating Proinflammatory Connective Tissue Growth Factor. Arthritis & rheumatology (Hoboken, NJ) 70 (11):1745-1756.[5] Tang X, et al. (2018) Connective tissue growth factor contributes to joint homeostasis and osteoarthritis severity by controlling the matrix sequestration and activation of latent TGFbeta. Ann Rheum Dis 77 (9):1372-1380.Fig 1.Distribution of serum CTGF in RA, other rheumatic diseases and healthy control. Serum sample were from 180 patients with rheumatoid arthritis (RA), 168 patients with other rheumatic diseases and 64 healthy individuals (HC). Levels of serum CTGF were measured by CTGF ELISA kit. The cut-off value was 263.30 pg/mL (black horizontal dotted line); ***p <0.001Table 1. Demographic, clinical and laboratory features of total RA patients and grouped with serum CTGF.Abbreviations: RA=rheumatoid arthritis; SJC=swollen joint count; TJC=tender joint count; ESR=erythrocyte sedimentation rate; CRP=C-reactive protein; DAS=disease activity score; CCP=cyclic citrullinated peptid; RF=rheumatoid factor. CTGF=connective tissue growth factor; ILD= interstitial lung diseaseDisclosure of Interests:None declared


2021 ◽  
Vol 9 ◽  
pp. 2050313X2097956
Author(s):  
Dorsa Zabihi-pour ◽  
Bahar Bahrani ◽  
Dalal Assaad ◽  
Jensen Yeung

Background: Palisaded neutrophilic granulomatous dermatitis is a rare inflammatory dermatosis with possible underlying systemic conditions including rheumatoid arthritis, autoimmune connective tissue disease, and malignancies. Case Summary: We report a case of an 84-year-old man presenting with a 3-week eruption of asymptomatic annular plaques on his neck, which progressed to involve his back and legs. Skin biopsies confirmed a diagnosis of palisaded neutrophilic granulomatous dermatitis, and he was treated with prednisone. Full workup related to potential underlying causes of palisaded neutrophilic granulomatous dermatitis was completed. Conclusion: Palisaded neutrophilic granulomatous dermatitis may precede the onset of underlying systemic conditions or occur concomitantly. Following the diagnosis, clinicians should perform a comprehensive focused history, physical examination, and laboratory investigation related to the associated underlying diseases.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1437.2-1438
Author(s):  
T. Kvlividze ◽  
V. Polyakov ◽  
В. Zavodovsky ◽  
Y. Polyakova ◽  
L. Seewordova ◽  
...  

Background:Interest in highly specialized tissue cytokines contributed to the discovery of new biologically active molecules. Nesfatin-1 (NF) - discovered in 2006 as an anorexigenic factor. NF-1 is believed to be involved in the regulation of energy homeostasis by regulating appetite and water intake. The role of NF-1 in the pathogenesis of inflammatory diseases is poorly understood. Recently, studies have found a relationship between an increased level of NF-1 and inflammatory markers in various pathologies.Objectives:Study of the level of nesfatin-1 in the blood serum of healthy people, determination of the correlation between the level of NF-1 with the severity of clinical symptoms and classic markers of inflammation in patients with RA.Methods:120 persons were examined: 90 patients with RA and 30 healthy people. All patients underwent a complete clinical and laboratory examination. Plasma NF-1 levels were determined using commercial test systems (RaiBiotech, cat # EIA-NESF) according to the manufacturer’s instructions. Patients with various forms of RA were comparable in age to the group of healthy individuals. Statistical processing of clinical examination data was carried out using the “STATISTICA 10.0 for Windows” software package. Quantitative data were processed statistically using the parametric Student’s t-test, qualitative data using the non-parametric chi-square test. The significance of differences between groups was determined using analysis of variance. The results were considered statistically significant at p <0.05.Results:The average level of NF-1 in blood serum in healthy individuals was 31.79 ± 3.21 ng / ml (M ± σ). The level of normal NF-1 values in healthy individuals, defined as M ± 2σ, ranged from 25.3 to 37.83 ng / ml. There was no significant difference in the levels of circulating NF-1 and BMI in healthy individuals and patients with RA (p> 0.05). The inverse relationship of a lower level of NF-1 with an increase in BMI was not significant.Group 1 (66 patients with RA) with increased serum NF-1 levels (> 37.83 ng / ml), and group 2 (44 patients) with normal values (<37.83 ng / ml). A high level of NF-1 was characteristic for patients with high activity according to DAS28, RF seropositive, ACCP-positive, with extra-articular manifestations, who had been ill for 10 years or more. A reliable relationship between the level of NF-1 in the blood serum and laboratory parameters of RA activity - ESR, CRP, was shown, and secondary synovitis was more common. Our data show a direct correlation between the NF-1 level of the pro-inflammatory markers of RA.Conclusion:The positive correlation between the level of NF-1 and classical markers of inflammation, such as CRP and ESR, confirms the involvement of NF-1 in the pathophysiology of inflammation in RA. This is also evidenced by the correlation of a high level of NF-1 in the blood serum with a more severe clinical picture of RA. It is known that NF-1 can promote the release of pro-inflammatory cytokines such as interleukin-8 (IL-8), interleukin-6 (IL-6), and macrophage inflammatory protein-1a (MIP-1a) in the chondrocytes of RA patients.It is necessary to further study the role of NF-1 in the pathogenesis of systemic inflammatory reactions and the possibility of targeting pro-inflammatory cytokines, the possibility of regulating the level of NF-1 by drugs.References:[1]Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R. Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R., Polyakova Yu.V., Sivordova L.E., Yakovlev A.T., Zborovskaya I.A. Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Klinicheskaya Laboratornaya Diagnostika (Russian Clinical Laboratory Diagnostics). 2019; 64 (1): 53-56 (in Russ.).Disclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 297.2-297
Author(s):  
Y. Akhverdyan ◽  
E. Papichev ◽  
В. Zavodovsky ◽  
L. Seewordova ◽  
J. Polyakova

Background:The main mechanism of the effect of fetuin-A (FeA) on bone metabolism is its ability to bind calcium and proteins of the TGF-β family. It has been proven that the optimal concentration of TGF-β is necessary for the differentiation of bone tissue, and a high concentration inhibits bone mineralization. Thus, adequate osteogenesis is based on a complex balance between FeA and TGF-β levels. It can be assumed that the determination of the FeA level in the blood of patients with rheumatoid arthritis (RA) will help to optimize the diagnosis and predict the severity of osteoporosis (OP).Objectives:to study the possibility of predicting the development of osteoporosis and osteoporetic fractures in patients with RA, depending on the level of FeA in blood serum.Methods:We examined two groups of patients (52 patients with RA complicated by OP, 58 patients with RA without OP) and 30 apparently healthy individuals. The age of the surveyed ranged from 18 to 72 years, the average duration of the disease was 7.53±0.89 years. In both groups, the FeA level was determined by an indirect enzyme-linked immunosorbent assay using a commercial test. Bone mineral density (BMD) was also measured in both groups (Lunar DPX-NT GE).Results:The average FeA level in the group of RA patients was lower than in the group of conventionally healthy individuals (731.21±109.9 μg/ml and 812.9±76.2 μg/ml, respectively; F=13.34; p=0,0004). The normal FeA level was calculated using the formula M±2σ in the group of apparently healthy individuals and ranged from 653.55 μg/ml to 972.19 μg/ml.A decreased level of FeA was found in 20 patients (86.96%) in the group of patients with OP and only in 3 (13.04%) patients with RA who did not suffer from OP (p<0.001). It can be concluded that patients with RA and a low concentration of FeA in the blood serum have a higher risk of developing OP.In the group of patients with normal FeA level, osteoporetic fractures were observed in 12 (13.79%) patients and were absent in 75 (86.21%) patients (p<0.001). Thus, RA patients with normal serum FeA levels have a lower risk of osteoporetic fractures.We also found a positive significant correlation between the level of FeA and BMD in the femoral neck area. In the group of patients with a reduced FeA level (23 people), the mean BMD values were 0.732±0.022 g/cm2, and in the group of patients with a normal FeA level (87 patients) - 0.890±0.014 g/cm2 (p<0.001, F=27.663). The obtained values are in agreement with the literature data on the effect of the serum FeA concentration on the BMD values.Conclusion:We consider it expedient to determine the serum FeA concentration in patients with RA. At a FeA level of 653.55 μg/ml and below, a higher risk of developing OP and osteoporetic fractures can be predicted. In this case, the patient is shown a standard examination for osteoporosis. At values of 653.55 μg/ml and above, a more expectant management of the patient is allowed. Thus, by determining the serum concentration of FeA, it is possible to implement an integrated approach to the patient and to optimize the schemes for the diagnosis of OP in patients with RA.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1350.1-1351
Author(s):  
O. Korolik ◽  
В. Zavodovsky ◽  
E. Papichev ◽  
Y. Polyakova ◽  
S. L ◽  
...  

Background:Cytokines stimulate the inflammatory response in the synovial membrane with rheumatoid arthritis (RA), initiate apoptosis of chondrocytes, activation of osteoclasts. The progression of comorbid diseases is also associated with the influence of cytokines. At the same time, anti-inflammatory cytokines are produced in various tissues. Their role in the pathogenesis of RA and its complications is ambiguous.Adiponectin (A) and Fetuin A (FA) are classified as negative acute phase proteins. Their concentration decreases with an increase in the level of pro-inflammatory cytokines: TNF-α, IL-1 and IL-6. Molecules A and FA, regardless of various factors and from each other, have similar effects in relation to pro-inflammatory cytokines, lipid and carbohydrate metabolism.Visfatin (V) and Nesfatin-1 (N-1) are pro-inflammatory adipokines. B is produced by cells of the mononuclear phagocytic system and connective tissue. N-1 - is produced by the cells of the intermediate and medulla oblongata and by the cells of the gastric mucosa.Objectives:to study the correlation of B, H-1, A and FA with the severity of inflammation in RAMethods:60 patients with RA and 30 healthy individuals were examined. The level of cytokines was determined by an indirect enzyme-linked immunosorbent assay using commercial test systems (Bio Vendor, cat No. RD195023100, Bio Vendor Human Fetuin-A, RaiBiotech, cat No. EIA-VIS-1, RaiBiotech, cat No. EIA-NESF). All patients underwent a full examination. Diagnosed with 2010 EULAR / ACR recommendations.Results:A decreased level of A (less than 0.8 μg/ml) was detected in 15 patients (25%), F-A (less than 653.55 μg/ml) in 16 (27%), a high level of V (more than 39 ng/ml) - in 55 (91%), N-1 (more than 37.95 ng/ml) - in 36 (60%), which is significantly more often than in healthy individuals. No significant difference in the levels of determined adipokines was found depending on the gender and body weight of patients with RA. The level of cytokines in RA is associated with high activity according to DAS 28, positivity by Anti-CCP, extraarticular manifestations of RA. The greatest correlation with extraarticular manifestations is with cutaneous and cerebral vasculitis. The levels of FA and N-1 also correlated with more pronounced radiological changes (X-ray stage III). FA circulating inhibitor of ectopic calcification. N-1 level is positively correlated with systolic blood pressure.Conclusion:A low level of A and FA, a high level of V and N-1 is characteristic of RA with the presence of high activity and positivity in the RF and Anti-CCP. An increased level of B is determined by more than 90% of patients, which indicates its high pro-inflammatory activity. The level of F and N-1 is also associated with the degree of damage to bone tissue (stage III, a lot of erosion). A positive correlation of level V and N-1, negative A and FA with the severity of inflammation in RA confirms the involvement of these proteins in the pathogenesis. A high level of A and V increases the risk of developing cardiovascular diseases and their complications, the effect of N-1 and FA is being studied. The effect of cytokines on osteoclasts and osteoblasts in RA is ambiguousReferences:[1]Visfatin and Rheumatoid Arthritis: Pathogenetic Implications and Clinical Utility. Polyakova Y. Curr Rheumatol Rev.2019[2]Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Kvlividze T. Klinicheskaya Laboratornaya Diagnostika.2019; 64 (1):53-56 (in Russ)[3]Fetuin-A. Novel hepatokine in rheumatoid arthritis laboratory diagnostics. Papichev E. Klinicheskaya Laboratornaya Diagnostika.2018; 63 (12):756-760 (in Russ)Disclosure of Interests:None declared


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