Jessica Miller1, Anne-Louise Ponsonby2, Angela Pezic1, Andrew Kemp1, Susan E Piper3, Jonathan D Akikusa4, Roger C Allen4, Jane E Munro4, Justine A Ellis2. 1. Murdoch Childrens Research Institute, Parkville, Victoria, Australia. 2. Murdoch Childrens Research Institute, Parkville, Victoria, Australia, and University of Melbourne, Melbourne, Victoria, Australia. 3. Monash Children's Hospital, Monash Medical Centre, Clayton, Victoria, Australia. 4. Murdoch Childrens Research Institute and Royal Children's Hospital, Parkville, Victoria, Australia.
Abstract
OBJECTIVE: Susceptibility to juvenile idiopathic arthritis (JIA) is presumed to be determined by both genes and environment. However, the environmental factors remain largely unknown. The hygiene hypothesis suggests that exposure to siblings, as a marker of exposure to microbes in early life, may protect against the development of later immune disorders. Some prior evidence suggests this may also be true for JIA. The present study was undertaken to test this hypothesis in detail. METHODS: We conducted a comprehensive analysis of the role of sibling exposure in JIA risk within the Childhood Arthritis Risk Factor Identification Study JIA case-hospital control sample (302 cases and 676 controls) from Victoria, Australia. RESULTS: We found that, compared to being an only child, having any siblings was protective against JIA, with an adjusted odds ratio (OR) of 0.46 (95% confidence interval [95% CI] 0.28-0.74) (P = 0.001). The protective association appeared to increase with increasing number of siblings (e.g., for ≥3 siblings, adjusted OR 0.25 [95% CI 0.13-0.48], P < 0.001). A protective association of siblings was also observed when we considered cumulative sibling years by age 6 (e.g., for ≥3 years of exposure versus no exposure, adjusted OR 0.49 [95% CI 0.30-0.79], P = 0.003). We also compared cases to a second control sample (n = 341) collected from the community and weighted to represent the child population of Victoria. Data remained supportive of an association between sibling exposure and protection against JIA, particularly for exposure to younger siblings. CONCLUSION: Increased exposure to siblings is associated with a reduced risk of disease in our sample. This suggests that increased microbial exposure in childhood may confer protection against the development of JIA.
OBJECTIVE: Susceptibility to juvenile idiopathic arthritis (JIA) is presumed to be determined by both genes and environment. However, the environmental factors remain largely unknown. The hygiene hypothesis suggests that exposure to siblings, as a marker of exposure to microbes in early life, may protect against the development of later immune disorders. Some prior evidence suggests this may also be true for JIA. The present study was undertaken to test this hypothesis in detail. METHODS: We conducted a comprehensive analysis of the role of sibling exposure in JIA risk within the Childhood Arthritis Risk Factor Identification Study JIA case-hospital control sample (302 cases and 676 controls) from Victoria, Australia. RESULTS: We found that, compared to being an only child, having any siblings was protective against JIA, with an adjusted odds ratio (OR) of 0.46 (95% confidence interval [95% CI] 0.28-0.74) (P = 0.001). The protective association appeared to increase with increasing number of siblings (e.g., for ≥3 siblings, adjusted OR 0.25 [95% CI 0.13-0.48], P < 0.001). A protective association of siblings was also observed when we considered cumulative sibling years by age 6 (e.g., for ≥3 years of exposure versus no exposure, adjusted OR 0.49 [95% CI 0.30-0.79], P = 0.003). We also compared cases to a second control sample (n = 341) collected from the community and weighted to represent the child population of Victoria. Data remained supportive of an association between sibling exposure and protection against JIA, particularly for exposure to younger siblings. CONCLUSION: Increased exposure to siblings is associated with a reduced risk of disease in our sample. This suggests that increased microbial exposure in childhood may confer protection against the development of JIA.
Authors: Anne-Louise Ponsonby; Angela Pezic; Fergus J Cameron; Christine Rodda; Andrew S Kemp; John B Carlin; Heikki Hyoty; Amirbabak Sioofy-Khojine; Terence Dwyer; Justine A Ellis; Maria E Craig Journal: PLoS One Date: 2018-04-17 Impact factor: 3.240
Authors: Christos Symeonides; Peter J Vuillermin; Emma Sciberras; Elizabeth Senn; Sarah M Thomson; Nicole Wardrop; Vicki Anderson; Angela Pezic; Peter D Sly; Anne-Louise Ponsonby Journal: BMJ Open Date: 2021-03-19 Impact factor: 2.692
Authors: Sarah L N Clarke; Katie S Mageean; Ilaria Maccora; Sean Harrison; Gabriele Simonini; Gemma C Sharp; Caroline L Relton; Athimalaipet V Ramanan Journal: Rheumatology (Oxford) Date: 2022-02-02 Impact factor: 7.580