Tumor necrosis factor-α -308 A/G gene polymorphism in children with juvenile idiopathic arthritis: relation to disease activity, damage, and functional status

Objective.Considering the relevance of tumor necrosis factor-α (TNF-α) in the pathophysiology of juvenile idiopathic arthritis (JIA), it is likely that polymorphisms in its promoter area may be relevant in disease susceptibility and activity. We investigated if clinical measures of JIA activity and TNF-α serum concentrations were associated with TNF-α −308 genotypes.Methods.Portuguese patients with JIA in 5 pediatric rheumatology centers were recruited consecutively, along with a control group of healthy subjects. Demographic and clinical data and blood samples were collected from each patient. DNA was extracted for analysis of TNF-α gene promoter polymorphisms at position −308 by restriction fragment-length polymorphism.Results.One hundred fourteen patients and 117 controls were evaluated; 57% of patients presented the oligoarticular subtype, 25% the polyarticular subtype, 8% the systemic subtype, and 9% had enthesitis-related arthritis and 5% psoriatic arthritis. Twenty-four percent of the patients presented the −308 GA/AA genotypes and 76% the −308 GG genotype, similar to findings in controls. Patients with the −308 GA/AA genotype had higher degree of functional impairment, erythrocyte sedimentation rate, 100-mm visual analog scale score for disease activity, and TNF-α levels compared to those with the −308 GG genotype.Conclusion.TNF-α −308 GA/AA genotypes were found to be related to higher inflammatory activity and worse measures of disease activity in Portuguese patients with JIA. They were not associated with susceptibility to JIA.

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FRI0374 PLASMA LEVELS OF 14-3-3 PROTEIN, S100A8/S100A9-PROTEIN, INTERLEUKIN-6, INTERLEUKIN-18, INTERLEUKIN-4, INTERLEUKIN-17, INTERLEUKIN-1Β AND TUMOR NECROSIS FACTOR-Α IN CHRONIC NON-BACTERIAL OSTEOMYEILITIS AND NON-SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6469 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 784.3-784

Author(s):

M. Kostik ◽

M. Makhova ◽

D. Kozlova ◽

D. Vasilyev ◽

L. Sorokina ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Tumor Necrosis Factor ◽

Interleukin 6 ◽

Plasma Levels ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Systemic Juvenile Idiopathic Arthritis ◽

Immune Mediated ◽

Factor Α ◽

Necrosis Factor

Background:Chronic non-bacterial osteomyelitis (CNO) is an immune-mediated disease associated with cytokine dysbalance.Objectives:The aim of our study was to evaluate the cytokines levels in CNO and compare to juvenile idiopathic arthritis (JIA) – disease with immune-mediated mechanism.Methods:The diagnosis of CNO made with criteria, proposed by Jansson (2007, 2009), after the exclusion of other causes of bone disease [1]. We included 42 patients with NBO, 28 patients with non-systemic juvenile idiopathic arthritis (JIA). We evaluated plasma levels of 14-3-3 protein, S100A8/S100A9-protein, interleukine-6 (IL-6), interleukine-18 (IL-18), interleukine-4 (IL-4), interleukine-17 (IL-17), interleukine-1β (IL-1 β) and tumor necrosis factor-α (TNFα) in 2 groups by the ELISA. Statistical analysis was carried out with Statistica 10.0 software. We utilized descriptive statistics (Me; IQR), Mann-Whitney tests.Results:We have found differences in the proinflammatory biomarkers between CNO, JIA. Patients with NBO had lower levels of studied cytokines, exclude14-3-3-protein, S100A8/S100A9 and interleukin-6 compare to JIA patients (table 1).Table 1.Comparison the cytokine levels between CNO, JIA NParameterNBO (n=42)JIA (n=28)pHemoglobin, g/l112 (104; 124)120 (114.5; 126.0)0.02WBC x 109/l7.9 (7.0; 10.5)8.0 (6.7; 10.0)0.86PLT x 109/l347 (259; 408)336.5 (274.0; 390.5)0.98ESR. mm/h25.0 (9.0; 46.0)8.5 (2.5; 13.0)0.013CRP, mg/l6.1 (0.6; 2.4)1.8 (0.4; 11.9)0.02714-3-3, ng/ml21.4 (18.5; 27.1)19.9 (18.0; 27.8)0.77S100A8/S100A9, ng/ml5.9 (5.2; 6.5)5.9 (5.0; 6.2)0.76IL-6, ng/ml126,2 (112.8; 137.5)132.4 (117.4; 142.9)0.16IL-18, ng/ml270.1 (200.1; 316.1)388.3 (373.9; 405.1)0.0000001IL-4, ng/ml15.3 (11.5; 18.2)18.7 (16.2; 20.2)0.003IL-17, ng/ml83.1 (71.1; 97.3)99.2 (87.3; 115.8)0.003IL-1b, ng/ml47.4 (42.0; 51.3)70.8 (65.3; 73.6)0.0000001TNFa, ng/ml19.4 (17.8; 21.3)23.1 (20.2; 25.9)0.0006Conclusion:Patients with CNO had less proinflammatory activity then JIA patients, besides IL-6 and S100A8/S100A9. Further investigations required for finding new more precise biomarkers and finding possible molecular targets for treatment.This work supported by the Russian Foundation for Basic Research (grant № 18-515-57001)References:[1]Jansson AF, et al. Clinical score for nonbacterial osteitis in children and adults. Arthritis Rheum. 2009;60(4):1152-9.Disclosure of Interests:None declared

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