scholarly journals AB0019 GENETIC POLYMORPHISM OF THE INFLAMMATORY MARKER SAA1 RS12218 (-13 T/C) IS ASSOCIATED WITH AN APTITUDE TO CLINICAL PHENOTYPES OF JUVENILE IDIOPATHIC ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1312.3-1313
Author(s):  
E. Fedorov ◽  
S. Salugina ◽  
M. Krylov ◽  
I. Guseva ◽  
E. Samarkina

Background:Juvenile idiopathic arthritis (JIA) is one of the most widely-spread immuno-inflammatory diseases of an unknown etiology, the leading manifestation of which is chronic joint inflammation, occuring in children under the age of 16. The disease is a complex of chronic arthropathies with various phenotypic manifestations.Objectives:To verify the hypothesis about the role of SAA1 rs12218 T / C gene polymorphism in the aptitude to various clinical JIA phenotypes.Methods:The study included 132 children, of whom 66 were diagnosed with JIA and 66 were healthy unrelated volunteers (the college students) as a control group, comparable by gender and age. The group of patients with JIA consisted of 44 girls and 22 boys, with an average age of 11.7 ± 4.2 years and an average disease duration of 4.8 ± 3.8 years. The diagnosis and classification of JIA was established according to ILAR-2004 criteria. The JIA group included 30 (45%) patients with oligoarthritis (oJIA), of which 20 patients (67%) were positive for the HLA-B27 antigen (JIA-B27 +) and 10 (33%) patients with anterior uveitis (uJIA); 20 (30%) patients were assigned to the group with the polyarticular variant (pJIA), while all of them were seronegative for the rheumatoid factor; 16 (24%) patients were diagnosed with JIA with a systemic onset (sJIA). The frequencies of the T / C polymorphism of the SAA1 gene were assessed using an allele-specific polymerase chain reaction in a real time mode (RT-PCR).Results:In the group of patients diagnosed with oJIA and (JIA-B27 +), the frequency of the C allele was significantly higher compared to the control (53.3% and 57.5% versus 37.1%, p = 0.035 and 0.022, respectively). No significant differences were detected in the frequencies of the mutant C allele between sJIA and pJIA and the control group. The logistics analysis of the frequency distribution of the alleles of the SAA1 gene demonstrated an increased risk of the C allele in formation of an aptitude to the oJIA variant (OR 1.94, 95% CI 1.00-3.76, p = 0.035). In the oJIA-B27 (+) group, the risk of an aptitude was also increased compared to the control (OR 2.29, 95% CI 1.05-5.04, p = 0.022).Conclusion:The data obtained confirm for the first time the involvement of the rs12218 polymorphism of the SAA1 gene in an aptitude to the oligoarthritis JIA clinical phenotype. The presented results require further replication researches using an enlarged number of patients from different population groups.Disclosure of Interests:None declared

Author(s):  
Iskander I. Zaidullin ◽  
Denis O. Karimov ◽  
Lilija K. Karimova ◽  
Milyausha F. Kabirova ◽  
Rasima R. Galimova ◽  
...  

The susceptibility to the development and progression of inflammatory periodontal diseases, which depends on genetic and external factors (smoking, stress, oral hygiene), varies widely. In the development of these diseases, an important role is played not only by the presence of periodontal pathogenic microorganisms, but also by the presence of congenital or acquired immunodeficiency, immunoregulatory defects. The immune system plays a key role in the physiological and pathological processes of periodontal tissues. In this regard, IL17, produced by CD4+ Th cells, which has both Pro-inflammatory and protective activity, is of particular interest in the pathogenesis of periodontitis. The aim of study was to identify the relationship between polymorphic loci of the IL-17A (rs2275913) and MMP-1 (rs1799750) genes and clinical manifestations of chronic periodontitis in petrochemical workers. Dental examination was performed in 92 ethylene oxide production workers with chronic periodontitis and 74 patients with chronic periodontitis who did not come into contact with chemical factors (control group). Genotyping of polymorphisms rs2275913 of the IL17A gene and rs1799750 of the MMP1 gene was performed by allele-specific real-time polymerase chain reaction (PCR). Hygienic assessment of the degree of air pollution of the working area with harmful substances was carried out by gas chromatography according to the guidelines for the determination of harmful substances in the air № 5098-89, № 3119-84. When comparing the results of studies of both groups, there were no statistically significant differences in the frequency distributions of allelic variants and genotypes of the IL-17A and MMP-1 genes. The AA/AG genotypes of the IL-17A gene were associated with an increased risk of severe disease compared to the GG genotype in workers in the main group (OR=6.1; 95% CI 1.33-28.5; p=0.021) and in the control group (OR=7.26; 95% CI 1.34-39.25; p=0.016). Carriers of the A allele in the control group increased the risk of severe chronic periodontitis by 2.4 times compared to carriers of the G allele (OR=2.41; 95% CI 1.19-4.87; p=0.014). During the dental examination of employees of the ethylene oxide plant, the clinical course of periodontal diseases was more severe in comparison with the control group, and the number of patients with severe periodontitis was twice as high. It was found that the AA/AG genotypes of the IL-17A gene and the carrier of the A allele are associated with increased susceptibility to the development of severe chronic periodontitis. The association between the MMP-1 gene polymorphism and the risk of severe forms of chronic periodontitis has not been established. A risk factor for the development of inflammatory periodontal diseases in employees of the petrochemical complex is a complex of harmful production factors.


2019 ◽  
Vol 13 (4) ◽  
pp. 55-60
Author(s):  
E. S. Fedorov ◽  
M. Yu. Krylov ◽  
S. O. Salugina ◽  
E. Yu. Samarkina ◽  
A. N. Latypova

Juvenile idiopathic arthritis (JIA) is a multifactorial immune-mediated inflammatory disease in childhood, the most common type of rheumatic disease in children. It is characterized by the polygenic type of hereditary predisposition.Objective: to study the association of STAT4 rs7574865 G/T and IRF5 rs2004640 G/T polymorphisms with the predisposition to certain JIA subtypes in the Russian pediatric population.Patients and methods. The investigation enrolled 177 patients, including 66 patients diagnosed with JIA and 111 healthy unrelated volunteers (a control group). Of the 66 patients with JIA there were 30 (45%) with oligoarthritis: 20 (67%) with human leukocyte antigen B27(HLA-B27)-positive JIA (that was associated with enthesitis, HLA-B27 positive JIA (JIA-B27), 10 (33%) with anterior uveitis concurrent with antinuclear antibody-positive JIA (JIA-uveitis); 20 (30%) with polyarticular JIA (JIA-poly), seronegative for rheumatoid factor; and 16 (24%) with systemic JIA (JIA-sys). As a control for genotyping STAT4 rs7574865 G/T and IRF5 rs2004640 G/T polymorphisms, the investigators studied 103 and 111 DNA samples from healthy adult volunteers, respectively. STAT4 rs7574865 G/T and IRF5 rs2004640 G/T polymorphisms were investigated using allele-specific real-time polymerase chain reaction (RT-PCR).Results and discussion. In the oligoarticular JIA group, the frequency of the STAT4 T allele was significantly higher than that in the control group (38.3 and 20.4%, respectively; p=0.004). This allele was also significantly more common in the JIA-B27 (35.0 and 20.4%, respectively; p=0.044) and JIA-uveitis (45.0 and 20.4%, respectively; p=0.021) groups compared with the control one. No significant differences were found in the frequency of the mutant STAT4 T allele between the control group and the JIA-sys and JIA-poly groups. Regression analysis showed that the identification of the STAT4 T allele was associated with the high risk of a predisposition to oligoarticular JIA as a whole (odds ratio, OR 2.43; 95% confidence interval (CI) 1.23–4.70; p=0.007), as well as to the antinuclear antibody-positive oligoarticular JIA with uveitis (JIA-uveitis): the risk in T allele carriers was 3.2 times higher than that in the control (OR 3.19; 95% CI 1.09–9.06; p= ). A high risk for predisposition was also found in the JIA-B27 subgroup compared with the control (OR 2.10; 95% CI 0.38–4.60; p=0.070). There were no statistical differences in the frequency of genotypes and alleles of the IRF5 rs2004640 G/T polymorphism between the entire group of JIA as a whole and its individual clinical types, as well as the control group.Conclusion. This pilot study confirmed that the STAT4 rs7574865 G/T polymorphism was associated with the risk of oligoarticular JIA, mainly that of JIA-uveitis and JIA-B27.


2019 ◽  
Vol 7 (1) ◽  
pp. 33-37
Author(s):  
Hakim Bahlok Jebur ◽  
Mirza Masroor ◽  
Hafiz Ahmad ◽  
Naushad Ahmad Khan ◽  
Juheb Akther ◽  
...  

BACKGROUND: C-reactive protein (CRP) is an inflammatory marker associated with T2DM, obesity, insulin resistance, and cardiovascular disease. AIM: The present study evaluates the association of CRP +1059 G/C polymorphism of the CRP gene in 100 T2D cases and 100 healthy controls. METHODS: Present study was done by allele specific PCR method to study the CRP gene polymorphism in study subjects. RESULTS: Study found that CRP (+1059 G/C) genotype distribution among case and controls was found to be significant (p=0.001), Higher CRP C allele frequency (0.16) was observed compared to controls (0.04). CRP +1059 GC and CC had 2.72 (1.12-6.61), 20.56 (1.16-362.1) risk for T2D. It has been observed, HTN, Obesity, Smoking and alcoholism was found to be associated with increased risk of T2D, and a significant difference was observed in biochemical parameters. CONCLUSION: Study concluded that CRP gene polymorphism was found to be associated with risk of Type 2 Diabetes and risk was linked with heterozygosity and mutant homozygosity. Hypertension, Obesity, Smoking and alcoholism increases the risk of occurrence of Type 2 Diabetes.


10.12737/5910 ◽  
2014 ◽  
Vol 21 (3) ◽  
pp. 100-104
Author(s):  
Апагуни ◽  
A. Apaguni ◽  
Бахадова ◽  
E. Bakhadova ◽  
Карпов ◽  
...  

The clinical and neuropsychological examination of 78 victims after suffering mine explosive wounds (MEW), which included 75 men and 3 women, was carried out. The 1st group consisted of the patients with MEW in combination with traumatic brain injury mild and accompanying complications – 51 (65,4%) patients; the 2nd group was the patients with MEW with peripheral lesion (limb amputation) – 27 (34,6%) patients. The basic number of patients were age 30-40 years (69,2%). The study identified the neurological changes that showed by the manifestation of brain syndrome, cerebral symptomatic, epilepsy syndromes, vegetative dystonia syndrome and its combinations. Average number of associated symptoms of vegetative dysfunction in the patients of the 1st and 2nd groups were significantly (p<0,05) higher relative to the control group. The authors note that the study of the vegetative nervous system identified supra-segmental disorders differed by poly-consistency and a high degree of expressiveness of vegetative dysfunction, with a significant (p<0,05) difference from the parameters of the control group. Disorders in the mental sphere and the failure of adaptation mechanisms in the form of increase of the level of fear and anxiety were identified. The most pronounced changes were observed in patients with MEW and brain injury. Identified dysfunction of the autonomic nervous system in most cases led to an increased risk of desadaptation, which further intensified manifestations of psychopathological disorders.


2017 ◽  
Vol 214 (11) ◽  
pp. 3449-3466 ◽  
Author(s):  
Alma-Martina Cepika ◽  
Romain Banchereau ◽  
Elodie Segura ◽  
Marina Ohouo ◽  
Brandi Cantarel ◽  
...  

The etiology of sporadic human chronic inflammatory diseases remains mostly unknown. To fill this gap, we developed a strategy that simultaneously integrates blood leukocyte responses to innate stimuli at the transcriptional, cellular, and secreted protein levels. When applied to systemic juvenile idiopathic arthritis (sJIA), an autoinflammatory disease of unknown etiology, this approach identified gene sets associated with specific cytokine environments and activated leukocyte subsets. During disease remission and off treatment, sJIA patients displayed dysregulated responses to TLR4, TLR8, and TLR7 stimulation. Isolated sJIA monocytes underexpressed the IL-1 inhibitor aryl hydrocarbon receptor (AHR) at baseline and accumulated higher levels of intracellular IL-1β after stimulation. Supporting the demonstration that AHR down-regulation skews monocytes toward macrophage differentiation, sJIA monocytes differentiated in vitro toward macrophages, away from the dendritic cell phenotype. This might contribute to the increased incidence of macrophage activation syndrome in these patients. Integrated analysis of high-dimensional data can thus unravel immune alterations predisposing to complex inflammatory diseases.


Open Medicine ◽  
2010 ◽  
Vol 5 (1) ◽  
pp. 36-40 ◽  
Author(s):  
Chris Pruunsild ◽  
Kaire Heilman ◽  
Kersti Zilmer ◽  
Karin Uibo ◽  
Hille Liivamägi ◽  
...  

AbstractTo examine the plasma levels of MPO in oligoarthritis and polyarthritis subtypes of JIA in comparison with healthy age-matched controls. Thirty-eight JIA patients (25 girls and 13 boys) aged 9.1–11.8 years and 23 healthy controls (8 girls and 15 boys) participated in the study. Twenty-one patients had oligoarthritis (8 with extended oligoarthritis) and 17 had polyarthritis (among them three were seropositive). The plasma concentration of MPO was measured by the ELISA technique (OxisResearchTM, BIOXYTECH® MPO-EIATM, Portland, OR USA). The mean plasma concentration of MPO in the JIA group was significantly higher than in the control group (76.6±24.8 µg/L versus 62.7±15.6 µg/L; p=0.01). Patients with polyarthritis presented a significantly higher mean plasma MPO level than patients with oligoarthritis (81.3±25.6 µg/L and 62.1±27.1 µg/L, respectively; p=0.02). Different subtypes of JIA may have different MPO-related backgrounds. MPO is a new potent inflammatory marker. Patients with polyarthritis have higher mean plasma MPO levels than patients with oligoarthritis and may therefore have an enhanced risk for subclinical oxidative stress-related atherogenic promotion.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1794.1-1795
Author(s):  
E. Tadiotto ◽  
C. Mansoldo ◽  
G. Bellisola ◽  
F. Caldonazzi ◽  
G. Aiello ◽  
...  

Background:Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatic disease. Its most threatening complication is represented by uveitis, which could cause severe visual impairment if not diagnosed and treated promptly. It is an asymptomatic uveitis and the diagnosis is only instrumental. Therefore, regular ophthalmologic surveillance is crucial in the management of JIA. To date there are no specific predictive markers of uveitis development among JIA patients, including serologic subsets. Anti-Nuclear Antibodies (ANA) positive patients have the highest risk of iridocyclitis, but ANA are not specific. They could be found in patients with JIA without uveitis, in many other rheumatologic and inflammatory conditions and also in healthy subjects (6-12% of children). Anti-DFS70 antibodies (ANA forming a specific pattern in immunofluorescence) have been taken into consideration, but their role has not yet been established in a pediatric setting. Currently, there are few reports, involving small groups of patients and with non-univocal results. Some studies report anti-DFS70 antibodies more frequently in children with rheumatological diseases, in particular JIA-related uveitis; on the contrary, others describe them in healthy ANA positive patients.Objectives:1) To evaluate the correlation between anti-DFS70 autoantibodies and the risk of developing uveitis in a cohort of patients with JIA ANA + in pediatric age;2) to compare the prevalence of anti-DFS70 in patients with JIA, with a group of healthy ANA + children, to better define the role of these autoantibodies (potential risk factor or a protective factor for the development of AARDs in children?)Methods:We evaluated retrospectively 51 patients with JIA ANA +. We divided these patients in two groups, according to the presence (n=11) or the absence (n=40) of uveitis. For each patient we evaluated: gender, current age, age at diagnosis, type of JIA, therapy, presence of other diseases, dosage of ANA (with IF-Hep2), research of anti-ENA and anti-DFS70 antibodies (with chemiluminescence). Subsequently the whole group of patients with JIA was compared with a control group of healthy subjects aged ≤ 18 years (n=30), followed in the pediatric rheumatology clinic for occasional finding of ANA positivity, without pathologies at the moment of the study (in particular without rheumatological or autoimmune diseases).Results:Among patients with JIA without uveitis, anti-DFS70 autoantibodies were positive only in one patient. Anti-DFS70 were negative in all patients with JIA and uveitis. The difference between the two groups is not significant (p=1). In the group of healthy patients 6/30 (20%) presented a positivity of anti-DFS70 autoantibodies, in the absence of anti-ENA.Conclusion:Our data revealed no correlation between the positivity of anti-DFS70 autoantibodies and the risk of uveitis in patients with JIA ANA +, even if the number of patients is small. Further studies are needed to identify a reliable predictive marker of uveitis risk in JIA patients. The finding of a significant greater prevalence of anti-DFS70 autoantibodies in healthy ANA + subjects allows to suppose that this autoantibody could represent a possible protective marker for development of AARDs in asymptomatic children with isolated ANA positivity, as for adults. To confirm this hypothesis, it would be useful to carry on the study prospectively, encompassing children with other rheumatological diseases, and prolonging the clinical and laboratory follow up.References:[1]Clarke S, Sen ES, Ramanan AV. Juvenile idiopathic arthritis-associated uveitis. Ped Reumatol 2016; 14: 27.[2]Seeling CA, Bauer O, Seeling H-P. Autoantibodies Against DFS70/LEDGF Exclusion Markers for Systemic Autoimmune Rheumatic Diseases (SARD). Clin. Lab 2016;62:499- 517.[3]Schmeling H et al. Autoantibodies to Dense Fine Speckles in Pediatric Diseases and Controls. The Journal of Rheumatology 2015;42(12):2419-2426.Disclosure of Interests:None declared


2019 ◽  
Vol 13 (2) ◽  
pp. 47-54
Author(s):  
E. V. Chetina ◽  
N. V. Demidova ◽  
G. A. Markova

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, which is characterized by chronic erosive arthritis (synovitis) and systemic inflammation of the viscera. Methotrexate (MTX) is the drug of choice for RA treatment. However, it is currently impossible to predict the efficacy of MTX in a particular patient; the drug fails to produce the desired effect or causes adverse reactions in a considerable number of patients. The identification of patients who are responsive to MTX could significantly improve the results of therapy.Objective: to investigate the specific features of baseline (pretreatment) expression of genes responsible for major metabolic and energy production pathways in RA patients with different disease activity and to identify the genes, the baseline expression of which could serve as a predictor for remission attainment.Patients and methods. Blood from 40 RA patients (mean age 47.5 years; mean disease duration 7.9 weeks) who had not previously received MTX and 26 healthy donors (mean age 45.1 years). All the patients had used MTX (15 mg/week) for 2 years. Clinical response was evaluated by DAS28 and the serum levels of anti-cyclic citrullinated peptide antibodies, C-reactive protein, and rheumatoid factor. Remission was diagnosed according to ACR/EULAR and DAS28 (DAS28 <2.6). Joint structural changes were radiographically evaluated. Gene expression was determined in peripheral blood cells by real-time reverse transcriptase-polymerase chain reaction. A control group consisted of 26 randomly recruited gender- and sex-matched patients without autoimmune diseases and a family history.Results and discussion. MTX treatment significantly decreased disease activity according to DAS28. At the end of the investigation, the majority of patients had moderate disease activity (3.2≤ DAS28 ≤5.1), 4 had high disease activity, while 12 attained remission (DAS28 <2.6). Gene expression analysis showed that RA patients who had achieved clinical remission after MTX therapy displayed higher baseline expression of the genes associated with glycolysis (Glut1, PKM), inflammation (TNF-α), autophagy (ULK1), apoptosis (caspase 3, p21), and hypoxia (HIF1α), compared with patients who had not attained remission and with healthy individuals. In addition, in patients who had achieved remission, the baseline expression of the CD1 gene was significantly higher than in healthy individuals, while in the remaining patients the expression of this gene was significantly lower than in the controls. While the disease activity remained high, the baseline expression of the p21, caspase 3, TGFβ1, and RUNX2 genes was significantly lower than in healthy individuals and other patients with RA.Conclusion. Remission achievement in RA patients who had not previously received MTX was associated with higher baseline (pretreatment) gene expression associated with glycolytic activity, inflammation, autophagy, apoptosis, and hypoxia compared with patients who failed to attain remission. Elevated baseline expression of the CD1 gene compared with that in healthy individuals may serve as a predictor of sensitivity to MT therapy. 


2021 ◽  
Author(s):  
Joanna Lipinska ◽  
Marcin Kaszkowiak ◽  
Beata Malachowska ◽  
Joanna Swidrowska-Jaros ◽  
Elzbieta Smolewska

Abstract AIM: The goal of the study was to assess the diagnostic and prognostic utility of survivin in patients with Juvenile Idiopathic Arthritis (JIA).METHODS: Seventy children with JIA – 59 newly diagnosed and 11 biologically treated (46 girls and 17 boys) aged 1.5-18 years and 29 healthy children as a control group, appropriately matched in terms of sex and age, were included into the study. The disease activity was established on the basis of JADAS-27 criteria. Concentration of survivin was assessed by an ELISA test in serum and also 18 matched synovial fluid samples collected from patients with JIA.RESULTS: Children with JIA were divided according to the subtype of the JIA. In 65.7% of patients oligoarthritis was diagnosed. The largest group comprised children of low disease activity (62.9%) according to JADAS-27. The serum concentration of survivin was significantly higher in children with JIA compared to the controls (p<0.001). Concentration of survivin was higher among patients positive for anti-cyclic citrullinated peptide autoantibodies (ACPA) (p=0.001). In all synovial fluid samples the concentration of survivin was higher than in matched serum (p=0.003). Serum survivin concentration was not significantly associated with radiological damage status or active synovitis assessed by joint ultrasonography. Survivin level was not significantly associated with disease duration time or treatment with TNF-α inhibitors in DMARD’s non-responders. CONCLUSIONS: Survivin should be considered as a biomarker of joint inflammation helpful in the diagnosis of oligo- and polyatricular JIA and probably not dependent of treatment with TNF-α inhibitors.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lina N. Zaripova ◽  
Angela Midgley ◽  
Stephen E. Christmas ◽  
Michael W. Beresford ◽  
Eileen M. Baildam ◽  
...  

AbstractJuvenile idiopathic arthritis (JIA) is the most common paediatric rheumatological disorder and is classified by subtype according to International League of Associations for Rheumatology criteria. Depending on the number of joints affected, presence of extra-articular manifestations, systemic symptoms, serology and genetic factors, JIA is divided into oligoarticular, polyarticular, systemic, psoriatic, enthesitis-related and undifferentiated arthritis. This review provides an overview of advances in understanding of JIA pathogenesis focusing on aetiology, histopathology, immunological changes associated with disease activity, and best treatment options. Greater understanding of JIA as a collective of complex inflammatory diseases is discussed within the context of therapeutic interventions, including traditional non-biologic and up-to-date biologic disease-modifying anti-rheumatic drugs. Whilst the advent of advanced therapeutics has improved clinical outcomes, a considerable number of patients remain unresponsive to treatment, emphasising the need for further understanding of disease progression and remission to support stratification of patients to treatment pathways.


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