Gut dysbiosis and inflammation in patients with Juvenile Idiopathic Arthritis-Enthesitis Related Arthritis: impact of HLA-B27 status.

BACKGROUND

HLA-B27 is a susceptibility factor for enthesitis-related arthritis. HLA-B27 transgenic rats do not develop disease in a germ-free state, suggesting involvement of the gut in the pathogenesis of the disease. There is limited data on the effect of HLA-B27 carriage and gut flora in JIA-ERA.

METHODS

Stool samples from 10 HLA-B27-positive and 5 HLA-B27-negative JIA-ERA patients, and 10 HLA-B27-negative healthy controls were collected after consent. Fecal calprotectin and serum LPS levels were measured using ELISA. The fecal flora was assessed using 16S rRNA based sequencing.

RESULTS

HLA-B27-positive patients had higher fecal calprotectin levels (p < 0.001) compared to HLA-B27-negative patients and HC. However, serum LPS levels were not different. Alpha and beta diversity of fecal flora were similar in HLA-B27-positive and negative patients, but different compared to HC. HLA-B27-positive patients had higher abundance of family Veillonellaceae, Prevotellaceae and genera Moryella, Intestinimonas, Fournierella, Leyella, Massiliprevotella, Segatella, and Bilophila and lower abundance of genera Bifidobacterium compared to HC. At the species level, the abundance of Coprococcus eutactus and Prevotella copri was higher while that of Dorea longicatena was lower in HLA-B27-positive patients compared to HC. In addition, there was lower abundance of the genera Fusicatenibacter and Lachnospiraceae NC2004 group, species belonging to genera Agathobacter, Fusicatenibacter, Butyricicoccus, and Acutalibacter and higher abundance of genera Leyella in HLA-B27-positive patients compared to HLA-B27-negative patients.

CONCLUSION

Lower abundance of anti-inflammatory and higher abundance of pro-inflammatory bacteria in HLA-B27-positive JIA-ERA patients by inducing gut inflammation may play a role in disease pathogenesis. Key Points • The presence of HLA-B27 in JIA-ERA patients is associated with a decline in the population of beneficial bacteria with anti-inflammatory properties and an increase in gut inflammation. • Exploration of supplementation with butyrate or SCFA to improve gut health may be beneficial in patients with JIA-ERA.