The Childhood Arthritis group group aims to better understand how nature (genes) and nurture (environment) come together to determine a person's risk of developing disease. The group focuses on childhood immune disorders, primarily juvenile idiopathic arthritis (JIA), for three reasons.
Firstly, we know that genes are involved in JIA. Secondly the occurrence of child immune disorders has increased at such a rate that this cannot be due only to genetic changes, but must also be due to changes in the environment. Thirdly, it is much easier to collect accurate information about environment from conception to disease onset from children and their families, than from adults where recall can be a significant issue.
Through its research, the group strives to better understand what causes JIA and also the ways in which genes and environment interact to cause human disease, particularly in childhood.
The interaction of genes and environment in JIA
In this National Health and Medical Research Council-funded project (2012-2014) the group aims to identify environmental factors which increase a child's risk of developing juvenile idiopathic arthritis (JIA). Researchers are focusing especially on the role of vitamin D and sun exposure, given growing evidence that this factor affects risk of developing other autoimmune diseases including multiple sclerosis. The researchers will then aim to determine how those factors interact with known JIA genes to better understand the ways in which 'nature and nurture' come together to cause disease.
The role of epigenetics in JIA
This project, supported by the Australian Research Council from 2012 to 2016, aims to discover whether epigenetic marks, specifically DNA methylation, are different in children with JIA (cases) compared to their healthy peers (controls). The team are currently looking at methylation in CD4+ T cells of cases with active disease, but will soon extend these analyses longitudinally to samples collected at birth, at diagnosis, and across the course of disease. They will also determine whether differences in gene methylation between cases and controls correlate with differences in gene expression.
The Paediatric AutoImmune Disease (PAID) platform
This collaborative project brings together researchers on campus studying paediatric autoimmune diseases, including juvenile idiopathic arthritis, type 1 diabetes, inflammatory bowel disease, and multiple sclerosis. Biospecimens (plasma, viably stored peripheral blood mononuclear cells, DNA) and environmental data are collected across cases for each disease in a harmonised fashion. A healthy child control sample is similarly collected, and shared amongst participating diseases as a comparison group. The overall aim of the PAID platform is to create a paediatric autoimmune disease research resource that will enable the discovery of genetic, epigenetic and environmental risk factors specific to each disease, along with identifying those risk factors common across diseases.
- Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry. 2018
- Epigenetic dysregulation of naive CD4+ T-cell activation genes in childhood food allergy. 2018
- Juvenile idiopathic arthritis managed in the new millennium: one year outcomes of an inception cohort of Australian children. 2018
- The DNA methylation landscape of CD4+T cells in oligoarticular juvenile idiopathic arthritis. 2018
- A survey of national and multi-national registries and cohort studies in juvenile idiopathic arthritis: challenges and opportunities. 2017
- Environmental and genetic determinants of two vitamin D metabolites in healthy Australian children. 2017
- Familial Analysis of Epistatic and Sex-Dependent Association of Genes of the Renin-Angiotensin-Aldosterone System and Blood Pressure. 2017
- Genetic variation at the Th2 immune gene IL13 is associated with IgE-mediated paediatric food allergy. 2017
- Association of juvenile idiopathic arthritis with PTPN22 rs2476601 is specific to females in a Greek population. 2016
- Fc-gamma receptor polymorphisms differentially influence susceptibility to systemic lupus erythematosus and lupus nephritis. 2016
- Genome-wide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA-DRB1. 2016
- MicroRNAs in CD4(+) T cell subsets are markers of disease risk and T cell dysfunction in individuals at risk for type 1 diabetes. 2016
- Polymorphisms affecting vitamin D-binding protein modify the relationship between serum vitamin D (25[OH]D3) and food allergy. 2016
- Sex bias in paediatric autoimmune disease - Not just about sex hormones? 2016
- Variants in CXCR4 associate with juvenile idiopathic arthritis susceptibility. 2016
- DNA methylation at IL32 in juvenile idiopathic arthritis. 2015
- Epistasis amongst PTPN2 and genes of the vitamin D pathway contributes to risk of juvenile idiopathic arthritis. 2015
- Genetic sharing and heritability of paediatric age of onset autoimmune diseases. 2015
- Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases. 2015
- Sibling Exposure and Risk of Juvenile Idiopathic Arthritis. 2015
- The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females. 2015
- Gene-environment interaction in autoimmune disease. 2014
- In vitro exposure of human blood mononuclear cells to active vitamin D does not induce substantial change to DNA methylation on a genome-scale. 2014
- Effects of NRG1 and DAOA genetic variation on transition to psychosis in individuals at ultra-high risk for psychosis 2013
- Independent replication analysis of genetic loci with previous evidence of association with juvenile idiopathic arthritis 2013
- Association analysis of oestrogen receptor beta gene (ESR2) polymorphisms with female pattern hair loss 2012
- CLARITY: ChiLdhood Arthritis Risk factor Identification sTudY. Paediatric Rheumatology 2012
- Stress-sensitive neurosignaling in depression: an integrated network biology approach to candidate gene selection for genetic association analysis 2012