Objective: To examine perinatal and childhood risk factors for the presence of rheumatoid factor in healthy children.
Methods: The Diabetes Autoimmunity Study in the Young (DAISY) is a longitudinal study of children at increased risk of type 1 diabetes, based on possession of human leucocyte antigen (HLA)-DR4 and DR3 alleles or a family history of diabetes. 651 children who participated in DAISY, with an average age of 6.4 (range 1–15) years, were tested for the presence of rheumatoid factor in their most recent serum sample. 23 children were positive for rheumatoid factor. Exposure data were collected prospectively by interview. HLA-DR4 alleles were identified using polymerase chain reaction-based Class II genotyping.
Results: While exploring risk factors for rheumatoid factor positivity in a multivariate model, several important interaction terms involving HLA-DR4 status suggested the need to evaluate risk factors in HLA-DR4-positive and HLA-DR4-negative children separately. In HLA-DR4-negative children, rheumatoid factor-positive infants were less likely to have been breast fed for >3 months (odds ratio (OR) 0.18; 95% confidence interval (CI) 0.04 to 0.99), more likely to have been exposed to non-parental tobacco smoke (OR 5.38; 95% CI 0.93 to 31.27) and more likely to be a race/ethnicity other than non-Hispanic white (OR 6.94; 95% CI 1.10 to 43.88) compared with rheumatoid factor-negative children, after adjusting for age, sex and maternal education. In HLA-DR4-positive children, there were no significantly associated risk factors for rheumatoid factor positivity.
Conclusions: Risk factors for rheumatoid factor positivity in children vary by HLA-DR4 genotype. In HLA-DR4-negative children, breast feeding may decrease the risk, and environmental tobacco smoke may increase the risk, of autoimmunity.
- BMI, body mass index
- DAISY, Diabetes Autoimmunity Study in the Young
- HLA, human leucocyte antigen
- JRA, juvenile rheumatoid arthritis
- T1DM, type 1 diabetes autoimmunity
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Funding: These studies were supported by National Institutes of Health Autoimmunity Prevention Center grants AI50864, R01 DK32493, and R01 DK49654, Diabetes Endocrine Research Center, Clinical Investigation and Bioinformatics core P30 DK57516, and the Smyth Professorship in Rheumatology.
Competing interests: None declared.
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