Dataset Information

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

ABSTRACT:

Background

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.

Methods

So measurement of PADI4 and IL-33 polymorphisms was conducted with 303 healthy controls, 144 JSLE patients and 160 JIA patients in this study.

Results

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.

Conclusions

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.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC9771228 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Zhou Yu Y Liu Xinle X

Medicine 20221201 50

<h4>Background</h4>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.<h4>Methods</h4>So measurement of PADI4 and IL-33 polymorphisms was conducted with 303 ...[more]

PMID: 36550815

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Project description:BackgroundThis 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).MethodWe 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.ResultsStudies 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.ConclusionThe 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.Prospero registration numberCRD42023391268.

Project description:Background: Systemic-Onset Juvenile Idiopathic Arthritis (SJIA) is a rare disease associated with dysregulated interleukin (IL)-1 activity. Objectives: To assess the efficacy and safety of Anakinra, an IL-1 receptor antagonist in SJIA and its effects on gene expression profiling. Methods: We conducted a multicenter, randomized, double-blind placebo-controlled trial. The primary objective was to compare the efficacy of a one-month treatment with anakinra (2 mg/kg subcutaneoulsy daily, maximum 100 mg) to a placebo between 2 groups of 12 SJIA patients each. Response was defined by a 30% improvement of the pediatric American College of Rheumatology criteria for JIA, resolution of systemic symptoms and a decrease of at least 50% of both C-reactive protein and erythrocyte sedimentation rate compared to baseline. An intention-to-treat analyze was performed. After Month 1 (M1), patients taking placebo were switched to Anakinra. Secondary objectives included tolerance and efficacy assessment for 12 months. Results: At M1, concluding the randomized trial, there was a significant difference in the response rate between patients treated with Anakinra (8/12 responders) and placebo (1/12) (p=0.003). The number of adverse events, mainly pain to injections, was similar between both groups. Ten patients from the placebo group switched to Anakinra at M1; nine were responders at M2. Between M1 and M12, six patients stopped treatment for an adverse event (Crohn’s disease, hepatitis), a lack of efficacy or a disease flare (2 cases each). Blood gene expression profiling at enrollment and upon follow-up allowed us to identify one set of dysregulated genes that reverted to normal values in the clinical responders and a second set, including interferon-inducible genes, that was induced by Anakinra. Conclusion: Anakinra is an effective treatment of SJIA. Its effect is associated with normalization of blood gene expression profiles in clinical responders and de novo induction of an interferon signature. (Clinical trials registration number: NCT00339157)

Project description:Systemic onset Juvenile Idiopathic Arthritis (SoJIA) represents up to 20% of Juvenile Idiopathic Arthritis (JIA). We have previously reported that this disease is Interleukin 1 (IL1)-mediated, and that IL-1 blockade results in clinical remission in the majority of patients. The diagnosis of SoJIA, however, still relies on clinical findings as no specific diagnostic tests are available, which leads to delays in the initiation of specific therapy. To identify specific diagnostic markers, we analyzed gene expression profiles in 19 pediatric patients with SoJIA during the systemic phase of the disease (fever and/or arthritis), 25 SoJIA patients with no systemic symptoms (arthritis only or no symptoms), 39 healthy controls, 94 pediatric patients with acute viral and bacterial infections (available under GSE6269), 38 pediatric patients with Systemic Lupus Erythematosus (SLE), and 6 patients with a second IL-1 mediated disease known as PAPA syndrome. Statistical group comparison and class prediction identified genes differentially expressed in SoJIA patients compared to healthy children. These genes, however, were also changed in patients with acute infections and SLE. By performing an analysis of significance across all diagnostic groups, we generated a list of 88 SoJIA-specific genes (p<0.01 in SoJIA and >0.5 in all other groups). A subset of 12/88 genes permitted us to accurately classify an independent test set of SoJIA patients with systemic disease. We were also able to identify a group of transcripts that changed significantly in patients undergoing IL-1 blockade. Thus, analysis of transcriptional signatures from SoJIA blood leukocytes can help distinguishing this disease from other febrile illnesses and assessing response to therapy. Availability of accurate diagnostic markers for SoJIA patients may allow prompt initiation of effective therapy and prevention of long-term disabilities. Keywords: Disease state analysis 123 RNA samples extracted from PBMCs were studied. For more details on the clinical information, please refer to the paper (PudMed ID...).

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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