Infections in infancy and the presence of antinuclear antibodies in adult life.
Edwards CJ., Syddall H., Goswami R., Goswami P., Dennison EM., Cooper C.
There has been limited success defining environmental factors important to the development of connective tissue diseases such as systemic lupus erythematosus (SLE). Recent work has suggested that the perinatal environment may be important. To investigate this we measured antinuclear antibodies (ANA) in a general population with well-defined early lives to see whether fetal and infant growth and infections were associated with ANA positivity in adult life. Included in our investigation were 1334 individuals (668 men, 666 women) from the Hertfordshire cohort study. ANA was measured using an ANA ELISA and confirmed using immunofluorescence. We investigated associations between the presence of ANA and early growth and infectious exposure in infancy in men and women combined, but with adjustment for gender throughout. A positive ANA was present in 73 (10.9%) of men and 81 (12.2%) women. Of these, 26 women and 14 men were positive using IF on HEP2 cells. Sharing a bedroom during childhood was associated with a higher risk of being ANA positive (odds ratio (OR), 1.42, 95% confidence interval (CI) 1.00-2.01, P = 0.05). A record of diarrhoeal illness (OR 2.12 95% CI 1.07, 4.23, P = 0.03) and rubella or mumps during the first year of life (OR 16.12, 95% CI 2.92, 88.94, P = 0.001) was also significantly associated with ANA in adult life. Higher ANA titres by Inova ELISA were associated with infections in the first year of life from mumps (2.74-fold higher, 95% CI 0.98, 7.64, P = 0.05) and rubella (3.90-fold higher, 95% CI 1.89, 8.04, P < 0.001). In addition, higher ANA titres were also associated with mumps (1.26-fold higher, 95% CI 1.02, 1.56, P = 0.03) between one and five years of age. Our results suggest that a developing immune system exposed to increased infection is more likely to produce ANA in adult life and perhaps begin the pathological process that leads to SLE.