Characterization of microbiota in systemic-onset juvenile idiopathic arthritis with different disease severities

BACKGROUND Systemic-onset juvenile idiopathic arthritis (SoJIA) is one of most serious subtypes of juvenile idiopathic arthritis. Although the pathogenesis of SoJIA remains unclear, several studies have suggested a correlation between gut dysbiosis and JIA. Further understanding of the intestinal microbiome may help to establish alternative ways to treat, or even prevent, the disease. AIM To explore alterations in fecal microbiota profiles in SoJIA patients and to evaluate the correlations between microbiota and clinical parameters. METHODS We conducted an observational single-center study at the Pediatric Department of Peking Union Medical College Hospital. Children who were diagnosed with SoJIA at our institution and followed for a minimum period of six months after diagnosis were recruited for the study. Healthy children were recruited as a control group (HS group) during the same period. Clinical data and stool samples were collected from SoJIA patients when they visited the hospital. RESULTS The SoJIA group included 17 active and 15 inactive consecutively recruited children;the control group consisted of 32 children. Firmicutes and Bacteroidetes were the two most abundant phyla among the total sample of SoJIA children and controls. There was a significant difference among the three groups in observed species, which was the highest in the Active-SoJIA group, followed by the Inactive-SoJIA group and then HS group (Active-SoJIA vs HS: P = 0.000;and Inactive-SoJIA vs HS: P = 0.005). We observed a lower Firmicutes/Bacteroidetes ratio in SoJIA patients (3.28 ± 4.47 in Active-SoJIA, 5.36 ± 8.39 in Inactive-SoJIA,and 5.67 ± 3.92 in HS). We also observed decreased abundances of Ruminococcaceae (14.9% in Active-SoJIA, 17.3% in Inactive-SoJIA, and 22.8% in HS;Active-SoJIA vs HS: P = 0.005) and Faecalibacterium (5.1% in Active-SoJIA, 9.9% in Inactive-SoJIA, and 13.0% in HS;Active-SoJIA vs HS: P = 0.000) in SoJIA compared with HS. By contrast, the abundance of Bacteroidaceae was the highest in the Active-SoJIA group, followed by the Inactive-SoJIA and HS groups (16.5% in Active-SoJIA, 12.8% in Inactive-SoJIA, and 9.7% in HS;Active-SoJIA vs HS: P = 0.03). The Spearman correlation analysis revealed a negative correlation between Proteobacteria or Enterobacteriaceae and juvenile arthritis disease activity score on 27 joints (JADAS-27). CONCLUSION The composition of the intestinal microbiota is different in SoJIA patients compared with healthy children. The dysbiosis presents partial restoration in inactive status patients.

Effect of etanercept on refractory systemic-onset juvenile idiopathic arthritis

Background:Treatment of systemic-onset juvenile idiopathic arthritis(So-JIA)is challenging,and the effi cacy of injectable recombinant human tumor necrosis factor type 1 receptor-antibody fusion protein(etanercept)on So-JIA has been controversial.Methods:We retrospectively studied 12 patients with refractory systemic juvenile arthritis treated with etanercept at our hospital in the past 5 years.The 12 patients were divided into a corticosteroid-dependent group(n=7)and an ineffective group(n=5)on the basis of their responses to treatment before the administration of etanercept.Etanercept was added to the treatment without substantially changing the original regimens in general,and doses,and signs of efficacy including alleviation or resolution of symptoms such as high fever,infl ammatory arthropathy,eruption rash,hydrohymenitis,as well as changes in the levels of laboratory infl ammatory markers such as the white blood cell count,erythrocyte sedimentation rate,levels of C-reactive protein and serum ferritin were recorded.Results:Etanercept was withdrawn after the first dose from one patient in the corticosteroid-dependent group because of a systemic allergic rash,and was also withdrawn from one patient in the ineffective group after 2 months of treatment owing to ineffi cacy;the remaining 10 patients completed the entire treatment protocol,at which point etanercept was discontinued.At that time,clinical symptoms and laboratory infl ammatory markers of the remaining patients were within the normal range and the mean dose of prednisone was 0.18 mg/kg per day,an 81%decrease from the mean dose at baseline.At present,the corticosteroid has been discontinued and only methotrexate maintenance treatment is used in 3 patients;the other 7 patients are treated with prednisone and methotrexate maintenance therapy.All of the 10 patients are in a medicated remission with no recurrence.Conclusions:In the treatment of patients with refractory So-JIA,the principles of individual therapy and combinations of drugs should be followed.Etanercept is an important and valid candidate for use in such combined treatment strategies.