The role of extracellular histones in systemic-onset juvenile idiopathic arthritis

Systemic onset juvenile idiopathic arthritis (SoJIA) encompasses ∼10% of cases of arthritis that begin in childhood. The disease is unique in terms of clinical manifestations, severity of joint involvement, and lack of response to tumor necrosis factor blockade. Here, we show that serum from SoJIA patients induces the transcription of innate immunity genes, including interleukin (IL)-1 in healthy peripheral blood mononuclear cells (PBMCs). Upon activation, SoJIA PBMCs release large amounts of IL-1β. We administered recombinant IL-1 receptor antagonist to nine SoJIA patients who were refractory to other therapies. Complete remission was obtained in seven out of nine patients and a partial response was obtained in the other two patients. We conclude that IL-1 is a major mediator of the inflammatory cascade that underlies SoJIA and that this cytokine represents a target for therapy in this disease.

Download Full-text

Faculty Opinions recommendation of Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1031253.793491940 ◽

2014 ◽

Author(s):

Timothy Beukelman

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Clinical Response ◽

Interleukin 1 ◽

Systemic Onset

Download Full-text

Relationship of genetic polymorphism of the acute phase marker of inflammation rs12218 of the SAA1 gene with clinical phenotypes of juvenile idiopathic arthritis

Modern Rheumatology Journal ◽

10.14412/1996-7012-2021-2-23-28 ◽

2021 ◽

Vol 15 (2) ◽

pp. 23-28

Author(s):

M. Yu. Krylov ◽

E. S. Fedorov ◽

S. O. Salugina

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Clinical Phenotype ◽

Control Group ◽

Chain Reaction ◽

Clinical Phenotypes ◽

Clinical Variants ◽

Polymerase Chain ◽

Relationship Of ◽

Systemic Onset

Objective: to test the hypothesis of a possible relationship between the rs12218 polymorphism of the SAA1 gene and a predisposition to different clinical phenotypes of juvenile idiopathic arthritis (JIA).Patients and methods. Genetic typing of rs12218 polymorphism was carried out in 142 children: 77 of them were diagnosed with JIA, including 30 patients with oligoarthritis (oJIA), 20 with polyarthritis (pJIA), and 27 with systemic onset (sJIA). Sixty five healthy volunteers were included in the control group. The rs12218 polymorphism of the SAA1 gene was investigated using real-time polymerase chain reaction.Results and discussion. A high risk of developing the clinical phenotype of oJIA in carriers of the C mutant allele of the rs12218 T/C polymorphism of the SAA1 gene was established. Statistically significant differences between the clinical phenotypes of oJIA and sJIA in the frequency distribution of genotypes and alleles of rs12218 T/C polymorphism of the SAA1 gene are shown.Conclusion. The results of the studies have confirmed the important role of the rs12218 T/C polymorphism of the SAA1 gene in the formation of susceptibility to clinical variants of JIA.

Download Full-text