Risk Of Juvenile Idiopathic Arthritis Research Articles

Relationships among gut microbiota, plasma metabolites, and juvenile idiopathic arthritis: a mediation Mendelian randomization study.

The objective of this study is to investigate the causal relationship between gut microbiota and juvenile idiopathic arthritis, and to identify and quantify the potential role of plasma metabolites as mediators. Using summary-level data from genome-wide association studies, a two-sample Mendelian randomization was conducted involving 131 gut microbiota genus, 1,400 plasma metabolites, and juvenile idiopathic arthritis. Additionally, a two-step approach was employed to quantify the proportion of the effect of gut microbiota on juvenile idiopathic arthritis mediated by plasma metabolites. Effect estimation primarily utilized Inverse Variance Weighting, with further validation using Bayesian weighted Mendelian randomization. In our MR analysis, a positive correlation was observed between Rikenellaceae and the risk of juvenile idiopathic arthritis, while Dorea showed a negative correlation with juvenile idiopathic arthritis risk. Mediation analysis indicated that Furaneol sulfate levels acted as a mediator between Dorea and juvenile idiopathic arthritis, with an indirect effect proportion of 19.94, 95% CI [8.86-31.03%]. Our study confirms a causal relationship between specific microbial genus and juvenile idiopathic arthritis, and computes the proportion of the effect mediated by plasma metabolites, offering novel insights for clinical interventions in juvenile idiopathic arthritis.

Etiological Theories of Juvenile Idiopathic Arthritis (JIA): A Narrative Review

Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease. It can be classified by diverse clinical presentations across subtypes classified by inflammation, swelling, and pain. This review examines current perspectives on factors impacting JIA etiology and future areas of development. Genetic and environmental factors, including early-life nutrition (i.e. breastmilk), mode of infant delivery, antibiotic exposure, and infections have been proposed as etiological candidates in the literature. Various human leukocyte antigen (HLA) genes and non-HLA genes related to immune signaling are risk factors for specific JIA subtypes. The impact of infection on JIA development has also been examined; it remains unclear whether infection plays a protective or harmful role. Moreover, shorter durations of breastfeeding during childhood may be associated with an increased risk of JIA development, given that breast milk consumption favorably increases bifidobacterium, changes the composition of the microbiome, and increases microbial diversity. Additionally, mode of delivery can play a role in the onset of JIA as birth delivery through Cesarean section puts children at a higher risk of JIA compared to infants born vaginally. Lastly, antibiotic exposure and its dose- and timedependent relationship also play a role in the microbiome and JIA pathogenesis. This research is significant, as an increased understanding of the etiology of clinically heterogeneous JIA subtypes may improve future treatments. Current limitations, research gaps, and future directions in the field are also discussed.

Роль вітаміну D при ювенільному ідіопатичному артриті

Considering the role of vitamin D in mineral metabolism and its extracellular effects, including immunomodulation with a tendency to suppress the immune response, there is significant interest in determining its role in developing autoimmune diseases, including juvenile idiopathic arthritis (JIA). Purpose - to determine the role of vitamin D in the development and course of JIA based on a systematic analysis of literature sources over the last 7 years. A search was conducted on PubMed for articles on the role of vitamin D in the development and course of JIA, using combinations of the following terms: “vitamin D” and “juvenile idiopathic arthritis”. The review included scientific publications with available full texts published from January 2017 to August 2023. The analysis results showed significant variations in the level of 25(OH)D among patients with JIA, and the vitamin D status in the majority of JIA patients was not optimal. However, the percentage of patients with suboptimal levels and vitamin D deficiency, according to the majority of studies, was not more significant than in the general population. Nevertheless, a correlation was found between low 25(OH)D concentration and high activity of JIA. Additional vitamin D supplementation did not impact the reduction of JIA activity or the improvement of indicators of bone mineral density. However, some publications emphasize the positive effect of sun exposure in reducing the risk of JIA. Further research is needed to clarify the necessity of additional vitamin D supplementation involving a larger number of patients, standardization, selection of optimal doses, and treatment duration. No conflict of interests was declared by the authors.

Inflammatory arthritis and eye diseases: a Mendelian randomization study.

The aim of this study was to determine causal associations between inflammatory arthritis and eye diseases (disorders of sclera, cornea, iris, and ciliary body [DSCIC] and disorders of choroid and retina [DCR]). Genome-wide association studies' summary data of rheumatoid arthritis (RA) from a large-scale meta-analysis were used to identify genetically predicted RA. UK Biobank source data predicted ankylosing spondylitis (AS), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA). Furthermore, data from the FinnGen Biobank were used to identify genetically predicted eye diseases. Two-sample Mendelian randomization analysis was used to assess the causal relationship between inflammatory arthritis and eye diseases in the European population. Inverse-variance weighting (IVW) was used as the primary method, while MR-Egger, weighted median, and MR-PRESSO outlier test were used to detect heterogeneity and pleiotropy. Genetically determined RA was indeed observed to have a causal effect on DSCIC (odds ratio [OR] = 1.084, p = 2.353 × 10-10) and DCR (OR = 1.151, p = 1.584 × 10-19). AS was causally associated with DSCIC (OR = 1.068, p < 2.024 × 10-8). In addition, PsA was also found to have a causal association with an increased risk of 17.9% for the development of DSCIC (OR = 1.179, p = 0.003). On the flip side, DSCIC increased the risk of JIA (OR = 2.276, p = 0.003). Our study provided genetic evidence for the causal associations of RA, AS, and PsA with an increased risk of DSCIC, and a causal association between RA and DCR was also identified. In addition, DSCIC greatly increased the risk of JIA.

IL12B and IL17 genes polymorphisms associated with differential susceptibility to juvenile idiopathic arthritis and juvenile-onset systemic lupus erythematosus in Chinese children

Genetic factors play a crucial role in the immune response of juvenile idiopathic arthritis (JIA) and juvenile-onset systemic lupus erythematosus (JSLE). This study aimed to investigate the association of IL12B (rs3212227, rs6887695) and IL17 (rs2275913, rs763780) gene polymorphisms with the susceptibility of JIA and JSLE in Chinese children. A total of 303 healthy controls and 304 patients including 160 JIA and 144 patients were analyzed, and the genetic polymorphisms were genotyped by using a Sequenom MassArray system. There was a significant association between the IL12B rs3212227 genotype and the increased risk of JSLE (P = .01). For rs6887695, the minor allele C was significantly associated with the increased risk of JIA (odds ratio = 1.48, 95% confidence interval [CI] = 1.12–1.95, P = .005). Moreover, rs6887695 genotype was significantly associated with both JIA and JSLE susceptibility (P &lt; .05). Besides, IL12B haplotype GC significantly associated with the increased risk of JIA (P = .016). However, no significant difference was found between the IL17 (rs2275913, rs763780) gene polymorphisms and JIA or JSLE susceptibility (P &gt; .05). And similar genotype distributions of IL12B and IL17 polymorphisms were found between the patients with nephritis and without nephritis in JSLE (P &gt; .05). Our results indicated that IL12B polymorphisms was associated with an increased risk for the development of JIA and JSLE in Chinese children, highlighting the involvement of inflammation in the pathogenesis of JIA and JSLE. Moreover, there was a risk haplotype in IL12B which could increase the risk of JIA.

Antibiotic exposure in prenatal and early life and risk of juvenile idiopathic arthritis: a nationwide register-based cohort study

ObjectivesEarly antibiotic exposure influences the gut microbiota which is believed to be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). We aimed to investigate the association between systemic antibiotics...

A systematic review and meta-analysis of environmental factors associated with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease, thought to be influenced by both genetics and the environment. Identifying environmental factors associated with disease risk will improve knowledge of disease mechanisms and ultimately benefit patients. This review aimed to collate and synthesize the current evidence of environmental factors associated with JIA. MEDLINE (Ovid), EMBASE (Ovid), Cumulative Index of Nursing and Related Health Literature (EBSCOhost), science network (WOS, Clarivate Analytics), Chinese National Knowledge Infrastructure, and Chinese Biological Medical Database were systematically searched. Study quality was rated using the Newcastle-Ottawa Scale. Pooled estimates for each environmental factor were generated using a random-effects, inverse-variance method, where possible. The remaining environmental factors were synthesized in narrative form. This review includes environmental factors from 23 studies (6 cohorts and 17 case-control studies). Cesarean section delivery was associated with increased JIA risk (pooled relative risk [RR] 1.103, 95% CI 1.033-1.177). Conversely, maternal smoking of more than 20 cigarettes/day (pooled RR 0.650, 95% CI 0.431-0.981) and gestational smoking (pooled RR0.634, 95% CI 0.452-0.890) were associated with decreased JIA risk. This review identifies several environmental factors associated with JIA and demonstrates the huge breadth of environmental research. We also highlight the challenges of combining data collected over this period due to limited study comparability, evolution in healthcare and social practices, and changing environment, which warrant consideration when planning future studies.

Juvenile idiopathic arthritis-associated genetic loci exhibit spatially constrained gene regulatory effects across multiple tissues and immune cell types

Juvenile idiopathic arthritis (JIA) is an autoimmune, inflammatory joint disease with complex genetic etiology. Previous GWAS have found many genetic loci associated with JIA. However, the biological mechanism behind JIA remains unknown mainly because most risk loci are located in non-coding genetic regions. Interestingly, increasing evidence has found that regulatory elements in the non-coding regions can regulate the expression of distant target genes through spatial (physical) interactions. Here, we used information on the 3D genome organization (Hi-C data) to identify target genes that physically interact with SNPs within JIA risk loci. Subsequent analysis of these SNP-gene pairs using data from tissue and immune cell type-specific expression quantitative trait loci (eQTL) databases allowed the identification of risk loci that regulate the expression of their target genes. In total, we identified 59 JIA-risk loci that regulate the expression of 210 target genes across diverse tissues and immune cell types. Functional annotation of spatial eQTLs within JIA risk loci identified significant overlap with gene regulatory elements (i.e., enhancers and transcription factor binding sites). We found target genes involved in immune-related pathways such as antigen processing and presentation (e.g., ERAP2, HLA class I and II), the release of pro-inflammatory cytokines (e.g., LTBR, TYK2), proliferation and differentiation of specific immune cell types (e.g., AURKA in Th17 cells), and genes involved in physiological mechanisms related to pathological joint inflammation (e.g., LRG1 in arteries). Notably, many of the tissues where JIA-risk loci act as spatial eQTLs are not classically considered central to JIA pathology. Overall, our findings highlight the potential tissue and immune cell type-specific regulatory changes contributing to JIA pathogenesis. Future integration of our data with clinical studies can contribute to the development of improved JIA therapy.

PADI4 and IL-33 gene polymorphisms with susceptibility to systemic lupus erythematosus and juvenile idiopathic arthritis, a systematic review and meta-analysis.

This study evaluated the association between peptidyl arginine deiminase type IV (PADI4) and interleukin 33 (IL-33) with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA). We searched the PubMed, Web of Science, Embase and Cochrane Library databases to retrieve articles published up to January 20, 2023. Stata/SE 17.0 (College Station, TX) software was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). The cohort study, case-control study focusing on the PADI4, IL-33 polymorphism, and SLE, JIA were retrieved. The data included basic information of each study and the genotypes and allele frequencies. Studies in PADI4 rs2240340 = 2 and 3 IL-33(rs1891385 = 3, rs10975498 = 2, rs1929992 = 4) were found in 6 articles. Overall, only the IL-33 rs1891385 show significant association between SLE in all 5 models. The results were OR (95% CI) = 1.528 (1.312, 1.778), P = .000 in Allele model (C vs A), OR (95% CI) =1.473 (1.092, 1.988), P = .000 in Dominant model (CC + CA vs AA), 2.302 (1.583, 3.349), P = .000 in Recessive model (CC vs CA + AA), 2.711 (1.845, 3.983), P = .000 in Homozygote model (CC vs AA), 5.568 (3.943, 7.863), P = .000 in Heterozygote model (CA vs AA). PADI4 rs2240340, IL-33 rs10975498, IL-33 rs1929992 were not found to be association with the risk of SLE and JIA. In gene model, statistically significant association was found between IL-33 rs1891385 and SLE in sensitivity analysis. Egger's publication bias plot showed there was no publication bias (P = .165). Only in recessive model the heterogeneity test was significant (I2 = 57.9%, P ≤ .093) of IL-33 rs1891385. The current study suggests that in all 5 model, IL-33 rs1891385 polymorphism may be associated with genetic susceptibility to SLE. There was unclear association found between PADI4 rs2240340, IL-33 rs10975498, and IL-33 rs1929992 polymorphisms and SLE and JIA. Due to the limitations of included studies and the risk of heterogeneity, additional research is required to confirm our findings. CRD42023391268.

Juvenile idiopathic arthritis in children and adolescents with atopic dermatitis: A Finnish nationwide registry study

Juvenile idiopathic arthritis in children and adolescents with atopic dermatitis: A Finnish nationwide registry study

Ассоциации гена VDR с клиническими проявлениями, осложнениями и обеспеченностью витамином D на фоне ювенильного идиопатического артрита у детей

Objective. To conduct an association search between genetic variants (c.1206T&gt;C, c.152T&gt;C, c.1174+283G&gt;A) of the VDR gene and clinical manifestations of juvenile idiopathic arthritis (JIA), need for genetically engineered biological drugs (GEBDs) and vitamin D status in children. Patients and methods. This study included 150 children (mean age: 9.11 ± 2.21 years) with JIA and 333 healthy controls. The determination of serum calcidiol concentrations was performed in all patients. Polymorphic variants of the VDR gene (c.1206T&gt;C, c.1175-9G&gt;T, c.152T&gt;C, c.1174+283G&gt;A) were tested by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) technique. Results. Carriers of the minor TT genotype of the genetic variant c.1206T&gt;C(A&gt;G) TaqI are 4 time more likely to develop systemic JIA, 5 time more likely to have high disease activity and uveitis, as well as 9.9 times more often require prescription of GEBDs. Carriers of the minor genotype TT of the genetic variant c.152T&gt;C FokI are 7.7 times more likely to develop systemic JIA and 4.3 times – polyarticular JIA, 6.2 times more likely to have high disease activity and 5.6 times – uveitis, 8 times more often have a severe calcidiol deficiency and 4 times more often require prescription of GEBDs. Carrying the minor AA genotype of the BsmlI polymorphism (c.1174+283G&gt;A) increases the risk of systemic-onset JIA by 17 times, high disease activity and uveitis – by 18 times, and need for GEBDs – by 15 times; carrying the AA and GA genotypes increases the risk of calcidiol deficiency by 5 times and severe calcidiol deficiency by 9 times. Conclusion. All studied genetic variants of the VDR gene verifiably affect the development of clinical manifestations, complications, calcidiol levels and response to therapy in JIA. Key words: VDR gene, juvenile idiopathic arthritis, children, vitamin D, autoimmune disease

PADI4 and IL-33 gene polymorphisms associated with differential susceptibility to juvenile-onset systemic lupus erythematosus and juvenile idiopathic arthritis in Chinese children

Juvenile systemic lupus erythematosus (JSLE) and juvenile idiopathic arthritis (JIA) are two common types of autoimmune diseases in children with unclear pathogenesis. Both peptidyl arginine deiminase type IV (PADI4) and interleukin 33 (IL-33) are the key molecular involved in immune responses in autoimmune diseases. Usually, it may share the same risk genetic alleles for autoimmune diseases. So measurement of PADI4 and IL-33 polymorphisms was conducted with 303 healthy controls, 144 JSLE patients and 160 JIA patients in this study. It demonstrated that there was a significant association between PADI4 genotypes (rs2240340: CT, CT + CC), IL-33 genotype (rs1929992: TT) and JSLE susceptibility in Southwest China population. While no significant association with the risk of JIA were observed no matter at allelic or genotypic levels. Our study reveals the importance of PADI4 and IL-33 polymorphisms with JSLE risk and their roles in the development of the diseases need more further researches.

Impact of Kawasaki disease on juvenile idiopathic arthritis in real-world patients: A population-based cohort study.

Recent research has demonstrated the commonality of several biological markers between Kawasaki disease (KD) and juvenile idiopathic arthritis (JIA), including interleukin-1β and -6. Therefore, in this cohort study, we assessed whether KD increases the risk of JIA. This study enrolled 7009 patients with and 56 072 individuals without KD in the period 2010-2018 from Taiwan's National Health Insurance Research Database. On the basis of sex, age, and comorbidities, we executed propensity score matching at the ratio 1:8. The adjusted hazard ratio (aHR) for JIA was determined through multiple Cox regression. Stratified analysis and sensitivity tests were also employed. When adjusting for age, sex, and comorbidities, the JIA risk was noted to be 2.02-fold greater in children with KD than it was in those without (aHR: 2.02, 95% confidence interval: 1.12-3.67, p = 0.0205). The sensitivity test and subgroup analysis obtained consistent findings in the different sex and comorbidity subgroups. Children's risk of JIA is higher if they have KD. Pediatricians should consider the possibility of JIA in this population. More investigations are necessary to identify the pathological mechanisms that link JIA and KD.

Vitamin D Levels and Risk of Juvenile Idiopathic Arthritis: A Mendelian Randomization Study.

Observational studies report mixed findings regarding the association between vitamin D and juvenile idiopathic arthritis (JIA) incidence or activity; however, such studies are susceptible to considerable bias. Because low vitamin D levels are common within the general population and easily corrected, there is potential public health benefit in identifying a causal association between vitamin D insufficiency and JIA incidence. To limit bias due to confounding and reverse causation, we examined the causal effect of the major circulating form of vitamin D, 25-hydroxy vitamin D (25-[OH]D), on JIA incidence using Mendelian randomization (MR). In this 2-sample MR analysis, we used summary level data from the largest and most recent genome-wide association study of 25-(OH)D levels (sample size 443,734), alongside summary data from 2 JIA genetic studies (sample sizes 15,872 and 12,501), all from European populations. To test and account for potential bias due to pleiotropy, we employed multiple MR methods and sensitivity analyses. We found no evidence of a causal relationship between genetically predicted 25-(OH)D levels and JIA incidence (odds ratio 1.00 [95% confidence interval (95% CI) 0.76, 1.33] per SD increase in standardized natural-log transformed 25-[OH]D levels). This estimate was consistent across all methods tested. Additionally, there was no evidence that genetically predicted JIA causally influences 25-(OH)D levels (-0.002 SD change in standardized natural-log transformed 25-[OH]D levels per doubling odds in genetically predicted JIA [95% CI -0.006, 0.002]). Given the lack of a causal relationship between 25-(OH)D levels and JIA, population level vitamin D supplementation is unlikely to reduce JIA incidence.

Genetic association between the PTPN22, IRF5 and TYK2 gene variants and susceptibility to juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) refers to a group of chronic childhood arthropathies of unknown etiology. In the present study, the genetic association between the variants in PTPN22, IRF5 and TYK2 genes and susceptibility to JIA was investigated. The distributions of 16 variants in PTPN22, IRF5 and TYK2 genes were analyzed by direct sequencing in 378 patients with JIA and 378 healthy controls. Odds ratios and 95% confidence intervals were used to evaluate the association between the gene variants and JIA. The gene-gene interactions were investigated using multifactor dimensionality reduction. All allelic and dominant models of PTPN22 rs1214414, rs1214418, rs1746853, rs3765598 and rs3811021 were significantly associated with JIA risk (P<0.05). IRF5 rs10954213 in both allelic and dominant models, as well as the allelic model of rs2004640, was significantly related to JIA risk (P<0.05). In addition, the allelic, recessive and dominant models of TYK2 rs280500, rs280519, rs2304256 and rs12720270 were significantly related to JIA risk (P<0.05). In addition, three haplotypes (HC A G T C C, HC A G T T C and HC G T T C T ) in PTPN22 gene, three haplotypes (HD T A A, HI T A C and HD T G C) in IRF5 gene and two haplotypes (HA G G A T and HG A G G T) in TYK2 gene were associated with the risk of JIA (P<0.05). Furthermore, a three-way interaction between IRF5 rs10954213, rs2004640 and PTPN22 rs1214414 was shown to be associated with JIA risk. In conclusion, PTPN22 rs1214418, rs1746853, rs3765598, IRF5 rs2004640, TYK2 rs280500, rs2304256 and a three-way interaction between IRF5 rs10954213, rs2004640 and PTPN22 rs1214414 may be risk factors for JIA.

Analysis of chromatin data supports a role for CD14+ monocytes/macrophages in mediating genetic risk for juvenile idiopathic arthritis

IntroductionGenome wide association studies (GWAS) have identified multiple regions that confer genetic risk for the polyarticular/oligoarticular forms of juvenile idiopathic arthritis (JIA). However, genome-wide scans do not identify the cells impacted by genetic polymorphisms on the risk haplotypes or the genes impacted by those variants. We have shown that genetic variants driving JIA risk are likely to affect both innate and adaptive immune functions. We provide additional evidence that JIA risk variants impact innate immunity.Materials and methodsWe queried publicly available H3K4me1/H3K27ac ChIP-seq data in CD14+ monocytes to determine whether the linkage disequilibrium (LD) blocks incorporating the SNPs that tag JIA risk loci showed enrichment for these epigenetic marks. We also queried monocyte/macrophage GROseq data, a functional readout of active enhancers. We defined the topologically associated domains (TADs) encompassing enhancers on the risk haplotypes and identified genes within those TADs expressed in monocytes. We performed ontology analyses of these genes to identify cellular processes that may be impacted by these variants. We also used whole blood RNAseq data from the Genotype-Tissue Expression (GTEx) data base to determine whether SNPs lying within monocyte GROseq peaks influence plausible target genes within the TADs encompassing the JIA risk haplotypes.ResultsThe LD blocks encompassing the JIA genetic risk regions were enriched for H3K4me1/H3K27ac ChIPseq peaks (p=0.00021 and p=0.022) when compared to genome background. Eleven and sixteen JIA were enriched for resting and activated macrophage GROseq peaks, respectively risk regions (p=0.04385 and p=0.00004). We identified 321 expressed genes within the TADs encompassing the JIA haplotypes in human monocytes. Ontological analysis of these genes showed enrichment for multiple immune functions. Finally, we found that SNPs lying within the GROseq peaks are strongly associated with expression levels of plausible target genes in human whole blood.ConclusionsThese findings support the idea that both innate and adaptive immunity are impacted by JIA genetic risk variants.

Risk of Juvenile Idiopathic Arthritis and Rheumatoid Arthritis in Patients With Celiac Disease: A Population-Based Cohort Study.

Celiac disease (CD) is associated with many immune-mediated conditions, but a definitive epidemiological association between CD and juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) has not been established. We quantified the risk of JIA and RA among patients with CD using a population-based cohort. We identified patients diagnosed with biopsy-proven CD between 2004 and 2017 using data from a national histopathology cohort in Sweden. Each patient was matched by age, sex, calendar year, and geographic region to reference individuals in the general population. We calculated the incidence and estimated the relative risk, through Cox proportional hazards models, of JIA in individuals with CD aged <18 and of RA in individuals with CD aged ≥18. We identified 24,014 individuals with CD who were matched to 117,397 reference individuals from the general population. Among individuals aged <18, the incidence rate of JIA was 5.9 per 10,000 person-years in patients with CD and 2.2 per 10,000 person-years in the general population (n events = 40 and 73, respectively; hazard ratio [HR] 2.68, 95% confidence interval 1.82-3.95) over a follow-up of 7.0 years. Among individuals aged ≥ 18, the incidence of RA was 8.4 per 10,000 person-years in CD and 5.1 per 10,000 person-years in matched comparators (n events = 110 and 322, respectively; HR 1.70, 95% confidence interval 1.36-2.12) over a follow-up of 8.8 years. Among children with CD, JIA develops nearly 3 times as often as it does in the general population, and among adults with CD, RA occurs nearly 2 times as often. Clinicians caring for patients with CD with joint symptoms should have a low threshold to evaluate for JIA or RA.

Association between Interleukin-17F 7488A/G and 7383A/G polymorphisms and susceptibility to juvenile idiopathic arthritis

BackgroundInterleukin-17F (IL-17F), one of the cytokines, is crucial in the pathophysiology of juvenile idiopathic arthritis (JIA). Therefore, we aimed to determine the relation between IL17F 7488A/G and IL17F 7383A/G single-nucleotide polymorphisms and JIA susceptibility and to explain their impact on the disease activity.MethodsGenomic DNA of 70 patients with JIA and 70 age and sex-matched controls were extracted and typed for IL17F 7488A/G and IL17F 7383A/G single-nucleotide polymorphisms, using polymerase chain reaction with sequence-specific primers method, and compared between patients and controls.ResultsWhen compared to AA participants, children with the AG genotype of the IL17F 7488A/G and IL17F 7383A/G polymorphisms showed a substantially greater risk of JIA. Furthermore, children with the G allele were 2.8 folds more likely to have JIA than the A allele for IL17F 7488A/G polymorphism and 3.72 folds for IL17F 7383A/G polymorphism. Children with AG genotype of IL17F 7383A/G polymorphism were far more likely to have high activity JIA.ConclusionsThe G allele of both IL17F 7488A/G and IL17F7383 A/G polymorphisms is associated with increased JIA susceptibility, and JIA at High Disease Activity was more likely to develop in AG subjects of the IL17F 7383 A/G polymorphism.ImpactThe relationship between Interleukin-17F 7488A/G and 7383A/G polymorphisms and risk for JIA has not been recognized before.Impact of Interleukin-17F 7488A/G and 7383A/G genotypes on JIA disease activity.The G allele of both IL17F 7488A/G and IL17F7383 A/G polymorphisms are associated with increased JIA susceptibility.AG genotype of Interleukin-17F 7383 A/G polymorphism compared to AA patients, had a higher probability of developing JIA at a High Disease Activity (HDA) level.

Causal analysis of serum polyunsaturated fatty acids with juvenile idiopathic arthritis and ocular comorbidity.

To investigate the causal effects of plasma Polyunsaturated fatty acids (PUFAs) on the risk of juvenile idiopathic arthritis (JIA) and ocular comorbidity through Mendelian randomization (MR) analysis. Genetic variants (formerly single nucleotide polymorphisms, SNPs) that are strongly associated with PUFAs levels (P < 5×10-8) were selected as instrumental variables. Summary-level MR was performed with outcome estimates for JIA (n = 31,142) and JIA associated iridocyclitis (n = 94,197). The inverse variance-weighted (IVW) method was employed as the main approach to combine the estimation for each SNP. Two set of models with summary statistics were conducted and multiple sensitivity analyses were applied for testing of pleiotropic bias. In model 1, genetically predicted n-6 PUFAs linoleic acid (LA) and arachidonic acid (AA) were associated with lower and higher risk of JIA associated iridocyclitis using IVW (ORLA = 0.940, 95% CI: 0.895-0.988, P = 0.015; ORAA = 1.053, 95% CI: 1.007-1.101, P = 0.024). No such association was observed between each plasma PUFAs and JIA susceptibility (P > 0.05). In further MR analysis, results from model 2 also showed a consistent trend. Besides, multiple sensitivity analyses revealed that there was no obvious evidence for unknown pleiotropy (P > 0.05). Our MR study provides genetic evidence on the possible causality that plasma LA level might protect against JIA associated iridocyclitis, whereas AA was responsible for opposite effect.

Association of juvenile idiopathic arthritis with maternal infection: a case control study

ObjectiveMaternal infection has been posited as a risk factor for childhood autoimmune disease such as type I diabetes. Given that similar studies in JIA are scant, our objective was to evaluate the association between Juvenile Idiopathic Arthritis (JIA) and maternal infection.MethodsThis case–control study used an existing database that included 1290 JIA cases and 6072 controls matched on birth year. Maternal infection information was obtained from Washington State birth records. JIA diagnosis and categories were confirmed through chart review. Logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsJIA was not associated with maternal infection (OR = 1.02, 95%CI: 0.8–1.3). There was no association between JIA and maternal infection for persistent oligoarticular, RF negative polyarticular, or enthesitis-related JIA. There was suggestive evidence of an increased association of maternal infection with JIA in females in sex-stratified analysis.ConclusionsWe did not observe an increased risk of JIA in children exposed to maternal infection. Suggestive evidence of differential sex-specific results warrants further study.