OBJECTIVE: To evaluate the differential expression of RNA in blood monocytes in patients with Juvenile idiopathic arthritis (JIA) treated with TNF antagonists (TNFi), and to explore the effect and mechanism of gene expression on the efficacy of JIA. METHODS: A total of 29 children with JIA treated with methotrexate (MTX) and TNFi in Guangzhou Women and Children's Medical Center of Guangzhou Medical University from April 2021 to November 2023 were enrolled. After 6 months, the children were divided into two groups according to the treatment effect, i.e., 13 cases in the ineffective group and 16 cases in the effective group, the peripheral blood of the children was collected, the blood mononuclear cells were isolated for transcriptome sequencing, the differentially expressed genes between the groups were analyzed, the signaling pathways and metabolic pathways related to the efficacy of TNFi were analyzed by GO and KEGG enrichment, and the mechanism related to the efficacy of TNFi was explored. This study was approved by Medical Ethics Committee of the Guangzhou Women and Children's Medical Center of Guangzhou Medical University (Ethics No.: 2023-330B00). RESULTS: There was a statistically significant difference in the gender and age distribution between the two groups of children (P < 0.05), while no statistically significant differences were observed in disease duration, rheumatoid antibody levels, or JIA subtypes (P > 0.05). After sequencing data quality control and comparison of reference genomes, a total of 18 523 protein-coding genes were identified in all children's samples. A total of 705 differentially expressed genes (DEGs) were identified between the effective group and the invalid group through differential analysis, of which 579 were up-regulated in the effective group and 126 in the inactive group. GO function and KEGG pathway enrichment analysis showed that DEG was significantly enriched in 55 GO entries and 32 KEGG metabolic pathways, which were mainly related to IL-1β production and regulation, cytokine production and regulation, cytokine-cytokine receptor interaction, immune response regulation, and Toll-like receptor signaling pathway. CONCLUSION DEG between the effective and ineffective groups of TNFi treatment may be involved in the biological processes such as cytokine production and regulation, cytokine-receptor interaction, and immune response regulation, which will be helpful to predict the efficacy and prognosis of TNFi treatment for JIA.
Humans ; Arthritis, Juvenile/blood* ; Female ; Male ; Child ; Methotrexate/therapeutic use* ; Child, Preschool ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Transcriptome ; Adolescent ; RNA/genetics* ; Signal Transduction ; Gene Expression Profiling

Humans ; Arthritis, Juvenile/genetics* ; Intracellular Signaling Peptides and Proteins/genetics* ; Genetic Predisposition to Disease

OBJECTIVETo investigate the predisposing alleles of HLA-DRB1 genes in Han children with juvenile idiopathic arthritis (JIA) from Guangdong Province, China.

METHODSPolymerase chain reaction-specific sequence primers (PCR-SSP) method was used to type HLA-DRB1 subregions in 94 Han children with JIA and 226 Han healthy controls.

RESULTSThe frequency of HLA-DRB1*08 allele in the JIA group was significantly higher than that in the control group (P=0.0014, OR=2.26), in contrast, the frequency of HLA-DRB1*12 allele was significantly lower than that in the control group (P=0.032, OR=0.55). It was found that in children with So-JIA subset (P=0.023, OR=2.25) and polyarthritis JIA subset (P=0.034, OR=2.81), the allele HLA-DRB1*08 was expressed most commonly. The allele HLA-DRB1*15 was expressed in a lower frequency in children with So-JIA subset (P=0.049, OR=0.413) and oligoarthritis subset (P=0.045, OR=0.16) compared with that in the control group.

CONCLUSIONSHLA-DRB1*08 may be the susceptible allele of JIA, while HLA-DRB1*12 may be the protective allele of JIA in Han children from Guangdong Province. HLA-DRB1*08 is the susceptible allele of So-JIA and polyarthrits. HLA-DRB1*15 is the protective allele for systemic JIA and oligoarthritis.

Adolescent ; Adult ; Aged ; Alleles ; Arthritis, Juvenile ; genetics ; Female ; Genetic Predisposition to Disease ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Young Adult

OBJECTIVETo examine the expression of FLICE-inhibitory protein (FLIP) in juvenile idiopathic arthritis (JIA) and analyze its correlation with synovial inflammation.

METHODSThe expression of FLIP was assessed in 11 JIA and 3 normal synovial tissue samples by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The cell types expressing FLIP were further characterized, and the correlation of FLIP expression with the degree of synovial inflammation, as well as the activity of caspase 8 was then analyzed.

RESULTSRT-PCR revealed the expression of FLIP mRNA in all 11 JIA samples, but not in 3 normal synovial tissues. In JIA, FLIP expression could be found in both the lining and sublining layers, mainly in the macrophage-like cells. Moreover, the expression of FLIP in JIA synovial tissues was positively correlated with the degree of synovial inflammation (r = 0.563, P < 0.05).

CONCLUSIONThe expression of antiapoptotic FLIP in JIA synovial tissue and its correlation to accumulation of inflammatory cells in synovial tissue suggests that FLIP potentially extends the lifespan of synovial cells and thus contributes to the progression of joint destruction.

Adolescent ; Arthritis, Juvenile ; metabolism ; pathology ; CASP8 and FADD-Like Apoptosis Regulating Protein ; genetics ; metabolism ; Caspase 8 ; metabolism ; Child ; Female ; Humans ; Inflammation ; metabolism ; pathology ; Male ; Protein Isoforms ; genetics ; metabolism ; Synovial Membrane ; cytology ; metabolism ; pathology