AB0103 THE AMBIGUOUS ROLE OF TISSUE CYTOKINES IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS

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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AB0827 SERUM NESPHATIN-1 IN PATHOGENESIS RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2503 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1437.2-1438

Author(s):

T. Kvlividze ◽

V. Polyakov ◽

В. Zavodovsky ◽

Y. Polyakova ◽

L. Seewordova ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Blood Serum ◽

Inflammatory Cytokines ◽

Inflammatory Markers ◽

Healthy People ◽

Healthy Individuals ◽

Markers Of Inflammation ◽

High Level ◽

Pro Inflammatory Cytokines

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

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POS0169 FETUIN-A AS A MARKER OF OSTEOPOROSIS AND OSTEOPOROTIC FRACTURES IN PATIENTS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.753 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 297.2-297

Author(s):

Y. Akhverdyan ◽

E. Papichev ◽

В. Zavodovsky ◽

L. Seewordova ◽

J. Polyakova

Keyword(s):

Rheumatoid Arthritis ◽

Blood Serum ◽

Bone Mineralization ◽

Expectant Management ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Individuals ◽

High Concentration ◽

Mineral Density ◽

Fetuin A ◽

Apparently Healthy

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

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POS0451 SERUM FETUIN-A AND VISFATIN LEVELS IN WOMEN WITH RHEUMATOID ARTHRITIS DEPENDING ON DISEASE ACTIVITY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1244 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 455.2-456

Author(s):

Y. Akhverdyan ◽

В. Zavodovsky ◽

E. Papichev ◽

J. Polyakova ◽

L. Seewordova

Keyword(s):

Rheumatoid Arthritis ◽

Blood Serum ◽

Disease Activity ◽

Transforming Growth Factor ◽

Average Level ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Healthy Individuals ◽

Fetuin A ◽

Grade Ii

Background:In recent years, the systemic effects of a number of cytokines have been actively studied, in particular, fetuin-A is considered a negative protein of the acute phase response, and visfatin, on the contrary, affects the activation of the cytokine cascade and has a pro-inflammatory effect. Taking into account that women suffer from rheumatoid arthritis (RA) more often, we investigated the levels of fetuin-A and visfatin in the blood serum of females in comparison with a group of healthy individuals and depending on the activity of the disease.Objectives:to study the levels of fetuin-A and visfatin in the blood serum of women suffering from RA, depending on the activity of the diseaseMethods:The study included 110 women with RA and 30 apparently healthy individuals. The inclusion criteria were: a diagnosis of RA verified based on the criteria of the American College of Rheumatology/European Anti-Rheumatic League (ACR/EULAR) 2010. The patients’ age ranged from 18 to 90 years. The control group included 30 conventionally healthy individuals. Serum fetuin-A and visfatin levels were determined by indirect enzyme-linked immunosorbent assay using commercial kits. RA activity was determined by the DAS28-CRP index. Activity 0-I was in 33 (30%) patients, grade II in 67 (60.9%), grade III in 10 (9.09%) patients.Results:The normal level of fetuin-A was calculated using the formula M±2σ in the group of conventionally healthy individuals and ranged from 653.55 to 972.19 μg/ml. In patients with grade 0-I RA activity according to DAS28, the mean serum fetuin-A level was 843.92±130.73 μg/ml, in patients with grade II activity - 742.37±98.85 μg / ml, with III the degree of activity - 663.9±123.7 μg/ml (p<0.001).The average level of visfatin in the blood serum in healthy individuals was 2.43±0.17 ng/ml. The level of normal values of visfatin in healthy individuals, defined as M±2σ, ranged from 0 to 5.07 ng/ml. The average level of visfatin in patients with RA was 6.27±0.18 ng/ml, which is significantly higher than in healthy individuals (p<0.001).In patients with 0-I degree of RA activity according to DAS28, the average level of visfatin in blood serum was 4.94±0.02 ng/ml, in patients with degree II activity - 5.08±0.02 ng/ml, with III degree of activity - 6.82±0.23 ng/ml (p<0.001).Conclusion:Thus, the level of fetuin-A in the blood serum of patients with RA is significantly lower in the case of a high degree of disease activity. The level of visfatin in the blood serum in women with RA is significantly higher in patients with a higher degree of disease activity. Therefore, the concentration values of fetuin-A and visfatin in the blood serum of patients with RA can be used in an integrated assessment of the prognosis of disease activity.References:[1]Inoue K, Ikeda Y, Yamanaka S, et al. Serum fetuinA levels in patients with rheumatoid arthritis [abstract]. Atherosclerosis. 2002;9(Suppl 1):233. doi: 10-1016/s1567-5688(08)70930-9[2]Janssens K, ten Dijke P, Janssens S, et al. Transforming growth factor-beta1 to the bone. Endocrine Reviews. 2005;26(6):743-74. doi:10.1210/er.2004-0001[3]Polyakova J, Korolik O, Papichev E, et al. The role of «new» cytokines in the pathogenesis rheumatoid arthritis. Ann Rheum Dis. 2018; 78(2): 1497Disclosure of Interests:None declared

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Inhibition of the IL-18 Receptor Signaling Pathway Ameliorates Disease in a Murine Model of Rheumatoid Arthritis

Cells ◽

10.3390/cells9010011 ◽

2019 ◽

Vol 9 (1) ◽

pp. 11 ◽

Cited By ~ 1

Author(s):

Yuji Nozaki ◽

Jinhai Ri ◽

Kenji Sakai ◽

Kaoru Niki ◽

Koji Kinoshita ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Signaling Pathway ◽

Inflammatory Cytokines ◽

Bone Erosion ◽

Quantitative Polymerase Chain Reaction ◽

Joint Inflammation ◽

Type Ii Collagen ◽

Enzyme Linked Immunosorbent Assay ◽

Cytokine Signaling ◽

Pro Inflammatory Cytokines

Interleukin (IL)-18 expression in synovial tissue correlates with the severity of joint inflammation and the levels of pro-inflammatory cytokines. However, the role of the IL-18/IL-18 receptor-alpha (Rα) signaling pathway in autoimmune arthritis is unknown. Wild-type (WT) and IL-18Rα knockout (KO) mice were immunized with bovine type II collagen before the onset of arthritis induced by lipopolysaccharide injection. Disease activity was evaluated by semiquantitative scoring and histologic assessment. Serum inflammatory cytokine and anticollagen antibody levels were quantified by an enzyme-linked immunosorbent assay. Joint cytokine and matrix metalloproteinases-3 levels were determined by a quantitative polymerase chain reaction. Splenic suppressors of cytokine signaling (SOCS) were determined by Western blot analysis as indices of systemic immunoresponse. IL-18Rα KO mice showed lower arthritis and histological scores in bone erosion and synovitis due to reductions in the infiltration of CD4+ T cells and F4/80+ cells and decreased serum IL-6, -18, TNF, and IFN-γ levels. The mRNA expression and protein levels of SOCS3 were significantly increased in the IL-18Rα KO mice. By an up-regulation of SOCS, pro-inflammatory cytokines were decreased through the IL-18/IL-18Rα signaling pathway. These results suggest that inhibitors of the IL-18/IL-18Rα signaling pathway could become new therapeutic agents for rheumatoid arthritis.

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POS0380 HORMONES OF ADIPOSE TISSUE IN PATIENTS WITH RHEUMATOID ARTHRITIS WHO HAVE REDUCED BODY WEIGHT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1432 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 420.2-420

Author(s):

L. Arefeva ◽

G. Kravtsov ◽

V. Polyakov ◽

V. Kravtsov ◽

L. Seewordova

Keyword(s):

Rheumatoid Arthritis ◽

Weight Loss ◽

Body Weight ◽

Adipose Tissue ◽

Inflammatory Cytokines ◽

Rheumatic Diseases ◽

Clinical Signs ◽

Control Group ◽

Fetuin A ◽

Pro Inflammatory Cytokines

Background:Overweight in patients with rheumatic diseases is a condition that prolongs chronic inflammation and promotes synthesis and secretion of pro-inflammatory factors by adipose tissue, such as classical cytokines, tumor necrosis factor-α (TNF-α), adipokines (leptin, adiponektin, resistin) and other newly identified proinflammatory factors (fetuin A, nesfatin, hemerin, lipokain, serum amyloid protein 3) [1,2,3,4].Objectives:We investigated the relationship the effect of weight loss over 5 kg on the clinical manifestations of arthritis and hormones of adipose tissue serum levels in patients with rheumatoid arthritis (RA).Methods:We observed 80 female patients with RA (EULAR/ARA 2010 criteria) ranged in age from 39 to 69 years (mean age 51,72 ± 5,83 years) and the control group (60 healthy persons) with no complaints of pain in the joints over a lifetime, and without clinical signs of RA. Fetuin A, nesfatin, hemerin, leptin, adiponektin, resistin, visfatin level in serum was determined by ELISA-test using a commercial test systems.Results:As overweight patients were recruited in the study, hypocaloric diet low in animal fats and physiotherapy has been recommended to all participants. The positive dynamics in body weight loss over 5kg within 3 months has been achieved by 34 patients (27,2%). In RA patients with weight loss, a significant decrease in the serum level of pro-inflammatory cytokines (fetuin A, nesfatin, hemerin, leptin, adiponektin, resistin, visfatin (p<0.01)) and an increase in the quality of life according to the EQ-5D-5L (p<0.001) index were observed. This fact is probably explained by the decreased activity of inflammatory process after RA therapy and weight reduction.Conclusion:Thus, as a result of our study patients with RA with weight loss of more than 5 kg had more obvious pain relief than patients with the original weight. These findings suggest that there is a possible role of tissue pro-inflammatory cytokines in the pathogenesis of rheumatoid arthritis. All patients with RA with a BMI over 25 kg / m 2 are recommended to lower their weight to decrease the mechanical stress on the joints, and also to reduce the severity of inflammation and metabolic disorders.References:[1]Akhverdyan, Y. et al. The nicotinamide-phosphoribosiltransferase as a marker of systemic inflammation under osteoarthrosis // Klin Lab Diagn. 2017; 62(10):606-610.[2]Kravtcov, V. et al. High level of adipokines and overweight as factors contributing to osteoarthritis progression // Osteoporosis International, 2019. V.30 (2). S. 408.[3]Papichev, E. V. et al. Parameters of mineral-bone metabolism and fetuin-А level in patients with rheumatoid arthritis // Osteoporosis International, 2019. V.30 (2), S.381.[4]Polyakova J. et al. Tissue cytokines and their role in the pathogenesis of rheumatic diseases // Annal.Rheum.Diseases, 2019. Т. 30 (2), № S.387.Disclosure of Interests:None declared

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AB0097 TISSUE CYTOKINES AS NEW DIAGNOSTIC BIOMARKER OF BONE METABOLISM DISORDERS IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6711 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1348.2-1348

Author(s):

V. Kravtsov ◽

L. Arefeva ◽

S. L

Keyword(s):

Rheumatoid Arthritis ◽

Bone Mineral Density ◽

Bone Density ◽

Inflammatory Cytokines ◽

Bone Mineral ◽

Serum Adiponectin ◽

Mineral Density ◽

Fetuin A ◽

Normal Bone ◽

Pro Inflammatory Cytokines

Background:Bone mineral density and proteins/peptides determination in blood and urine as markers of bone resorption and formation are currently used to diagnose osteoporosis (OP) and metabolic bone diseases. Recent evidence suggests that in RA changes in the secretion of hormones of white adipose tissue can be revealed [1,2,3,4].Objectives:To study the clinical and diagnostic value of serum fetuin A, nesfatin, hemerin, leptin, adiponektin, resistin, visfatin determination in RA patients complicated by OP.Methods:We examined 88 women with documented diagnosis of RA and mean disease duration of 6.56±0.88 years. We used EULAR/ARA 2010 criteria to diagnose the patients. Female patients with II degree of disease activity (DAS28), Steinbrocker stage II (erosive), rheumatoid factor- and anti-cyclic-citrullinated peptide antibody-positive were prevalent. We excluded patients who had surgery or developed an infection within the last 8 weeks, pregnant and breast-feeding women, those with severe heart, liver or kidney disease, immune deficiency, leukopenia or chronic infection.A control group of 45 healthy females aged of 25 and 59 years were included in the study. There were no reported findings of joint pain and RA symptoms in the group. The groups were adjusted for age (p>0.05) and showed no statistically significant differences.We measured serum fetuin A, nesfatin, hemerin, leptin, adiponektin, resistin, visfatin levels (µg/ml) using ELISA commercial test systems. We used spectrophotometer with wavelength of 450 nm to detect the test results («Multiskan» immunoenzyme analyzer, Finland). We plotted a curve using computer software. We diagnosed OP using dual-energy X-ray absorptiometry with LUNAR DPX PRO (GE, USA).Results:At the first stage, the level of pro-inflammatory cytokines was studied in a group of healthy individuals. Then, the reference values of these indicators were measured as М ± 2δ. Patients with OP and RA had significantly higher levels of serum pro-inflammatory cytokines (р<0.001). For example, mean serum Adiponectin levels in RA patients who had normal bone density and had no OP were 35.21±0.6 µg/ml. Mean serum Adiponectin levels in RA/OP patients with low bone mineral density were 52.42±0.69 µg/ml. Adiponectin levels of 44 µg/ml and higher were associated with osteoporosis. Adiponectin levels of 43.9 µg/ml and lower were associated with normal bone density. Other pro-inflammatory cytokines have demonstrated similar dynamics of level serum.Conclusion:Thus, we revealed that fetuin A, nesfatin, hemerin, leptin, adiponektin, resistin, visfatin levels depend on osteoporosis presence in RA patients. The test may be used to reduce the risk of low-energy fractures and to improve the quality of life in RA.References:[1]Akhverdyan Y. et al. Laboratory markers of inflammation and serum nicotinamide phosphoribosyltransferase level in rheumatoid arthritis patients // Ann. Rheum. Dis., 2017, vol.76, suppl.2, p.1149.[2]Kvlividze Z. et al. Elevated nesfatin-1 levels in patients with rheumatoid arthritis // Ann Rheum Dis, 2018, vol.77, p.A1762.[3]Papichev E. et al. Fetuin-A: clinical and laboratory associations in women with rheumatoid arthritis // Ann Rheum Dis, 2018, vol.77, p.A1228.[4]Polyakova J. S. et al. Serum visfatin determination in rheumatoid arthritis // Ann. Rheum. Dis. 2014; 73 (Suppl2).Disclosure of Interests:None declared

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Systematic review of gut microbiota and attention-deficit hyperactivity disorder (ADHD)

Annals of General Psychiatry ◽

10.1186/s12991-021-00330-w ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Alverina Cynthia Sukmajaya ◽

Maria Inge Lusida ◽

Soetjipto ◽

Yunias Setiawati

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Gut Microbiota ◽

Inflammatory Cytokines ◽

Attention Deficit ◽

Healthy Individuals ◽

Case Control Studies ◽

Cultural Aspects ◽

Hyperactivity Disorder ◽

High Level ◽

Pro Inflammatory Cytokines

Abstract Background Gut–brain axis (GBA) is a system widely studied nowadays, especially in the neuropsychiatry field. It is postulated to correlate with many psychiatric conditions, one of them being attention-deficit hyperactivity disorder (ADHD). ADHD is a disorder that affects many aspects of life, including but not limited to financial, psychosocial, and cultural aspects. Multiple studies have made a comparison of the gut microbiota between ADHD and healthy controls. Our aims were to review the existing studies analyzing the gut microbiota between human samples in ADHD and healthy individuals. Methods The literature was obtained using Google Scholar, Pubmed, and Science Direct search engine. The keywords used were “ADHD”, “gut microbiota”, “stool”, “gut”, and “microbiota”. The selected studies were all case–control studies, which identify the gut microbiota between ADHD and healthy individuals. Result We found six studies which were eligible for review. The model and methods of each study is different. Forty-nine bacterial taxa were found, yet none of them can explain the precise relationship between ADHD and the gut microbiota. Bifidobacterium was found in higher amount in ADHD patients, but other study stated that the abundance of this genus was lower in ADHD with post-micronutrient treatment. This may suggest that micronutrient can modulate the population of Bifidobacterium and improve the behavior of ADHD patients. Other notable findings include a significantly lower population of Dialister in unmedicated ADHD, which rose after patients were medicated. A smaller amount of Faecalibacterium were also found in ADHD patients. This may explain the pathogenesis of ADHD, as Faecalibacterium is known for its anti-inflammatory products. It is possible the scarcity of this genera could induce overproduction of pro-inflammatory cytokines, which is in accordance with the high level of pro-inflammatory cytokines found in children with ADHD. Conclusion There were no studies that examined which bacterial taxa correlated most to ADHD. This might occur due to the different model and methods in each study. Further study is needed to identify the correlation between gut microbiota and ADHD.

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AB0167 PECULIARITIES OF INTERACTION OF CHRONIC INFLAMMATION AND DEPRESSION IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3087 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1110.1-1110

Author(s):

A. Aleksandrov ◽

N. Aleksandrova

Keyword(s):

Rheumatoid Arthritis ◽

Vitamin D ◽

Inflammatory Cytokines ◽

Depressive Disorders ◽

Severe Depression ◽

Mild Depression ◽

Group Iii ◽

Group I ◽

Severity Of Depression ◽

Pro Inflammatory Cytokines

Background:In patients with rheumatoid arthritis (RA), a high prevalence of depression and anxiety is observed, and the severity of these conditions depends on the degree of vitamin D deficiency. The role of the main mediator, with the help of which psychological and physical stress factors can contribute to the development of depression and systemic diseases, has been attributed to inflammation in recent years.Objectives:to assess the dependence of depressive disorders on vitamin D deficiency and the level of pro-inflammatory cytokines in patients with RA.Methods:88 women with a reliable diagnosis of RA (mean age 54.2 ± 12.0 years old, disease duration 9.0 [3.5; 16.0] years) were under observation. Beck’s depression inventory (BDI-II) was used to assess the presence of depressive symptoms. ELISA test was used to measure serum cytokines (IL-1, IL-6) and serum 25(OH)D levels.Results:The presence of depression was found in 66% of patients with RA. An insufficient level of 25(OH)D (<30 ng / ml) was determined in 89.8% of cases. In RA patients with no signs of depression, the level of 25(OH)D showed maximum values and significantly differed from that in the groups of patients with moderate (p = 0.028) and severe depression (p <0.001). A negative correlation (r = -0.38, n = 88, p <0.05) was established between the level of 25(OH)D and the severity of depression. A positive relationship was also found between 25(OH)D and ESR (r = 0.29, n = 73, p <0.05) and a negative relationship with the number of painful joints (r = -0.29, n = 76, p <0.05). Probably, vitamin D is indirectly involved in inflammatory processes in joints and in central sensitization, which provokes chronic pain and psychological disorders in patients with RA.The level of IL-6 in patients with RA with moderate and severe depression (n=18; 14.6 ± 6.7 pg/ml) significantly exceeded the parameters of patients with RA without depressive disorders (n=30; 9.8 ± 3.7; p = 0.003). There was also a tendency to increase IL-6 in the group of patients with moderate and severe depression compared with patients with mild depression (p = 0.06). IL-1β values significantly increased with the progression of depression (without depression – mild depression, p = 0.034; mild – moderate, p <0.001; moderate – severe depression, p = 0.044). A positive correlation of average severity was revealed between the degree of depression (according to BDI-II) and the dose of glucocorticoids (GC) at the time of the study (r = 0.33, p = 0.002). An increase in the GC dose in the short term can aggravate depressive disorders in RA patients (Table 1).Table 1.Indicators of levels of depression and IL-1β depending on the dose of GCGroup I (n=26), without GCGroup II (n=45),GC <10 mg / dayGroup III (n=17),GC ≥10 mg / dayDepression level according to BDI-II, points (Me [P25; P75])8,5[5;16]14[9;17]19[14;29] *III-IIL-1β level, pg / ml (M ± SD)4,57 ± 1,83*I-II6,04 ± 3,276,52 ± 5,16* - intergroup differences are reliable, p <0.05Patients who used GC in a daily dose of ≥10 mg / day (group III) had a higher degree of depression compared to patients with RA from group I (z = -2.98; p = 0.003). In patients with RA in the first group, the level of IL-1β was significantly higher (pI-II = 0.039) than in patients with GC prescription in minimal doses (up to 10 mg / day) (Table 1). Glucocorticoid hormones suppress pro-inflammatory cytokines. As a rule, this effect is not observed in patients with depression. This fact may indicate a violation of homeostatic mechanisms. IL-1β is thought to be the first step in the pro-inflammatory response to psychological stress and is capable of inducing a subsequent cascade of other inflammatory cytokine responses.Conclusion:Restoring the normal level of 25(OH)D in the blood serum of patients with RA can positively affect psychological indicators by reducing the severity of depression and manifestations of pain. The activation of pro-inflammatory cytokines during stress and depression suggests that suppression of the inflammatory response can also reduce the symptoms of depression in RA patients.Disclosure of Interests:None declared

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Proinflammatory Soluble Interleukin-15 Receptor Alpha Is Increased in Rheumatoid Arthritis

Arthritis ◽

10.1155/2012/943156 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Ana Cecilia Machado Diaz ◽

Araceli Chico Capote ◽

Celia Aurora Arrieta Aguero ◽

Yunier Rodríguez Alvarez ◽

Diana García del Barco Herrera ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Enzyme Linked Immunosorbent Assay ◽

Reverse Signaling ◽

Synovial Fluids ◽

Inflammatory Processes ◽

Membrane Bound ◽

Interleukin 15 ◽

Interleukin 15 Receptor Alpha ◽

Pro Inflammatory Cytokines

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease in which many cytokines have been implicated. In particular, IL-15 is a cytokine involved in the inflammatory processes and bone loss. The aim of this study was to investigate the existence in synovial fluid of soluble IL-15Rα, a private receptor subunit for IL-15 which may act as an enhancer of IL-15-induced proinflammatory cytokines. Soluble IL-15Rα was quantified by a newly developed enzyme-linked immunosorbent assay (ELISA) in samples of synovial fluid from patients with RA and osteoarthritis (OA). The levels of IL-15Rα were significantly increased in RA patients compared to OA patients. Also, we studied the presence of membrane-bound IL-15 in cells from synovial fluids, another element necessary to induce pro-inflammatory cytokines through reverse signaling. Interestingly, we found high levels of IL-6 related to high levels of IL-15Rα in RA but not in OA. Thus, our results evidenced presence of IL-15Rα in synovial fluids and suggested that its pro-inflammatory effect could be related to induction of IL-6.

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