Neonatal cytokine profiles and risk of childhood acute lymphoblastic leukemia

[[abstract]]Purpose: Childhood acute lymphoblastic leukemia (ALL) is hypothesized to originate from abnormal immune responses to infectious agents resulting from lack of immune modulation during early childhood. It has been shown that a child's immune development begins in utero, and that a child's baseline immune function at birth may affect his/her response to subsequent infectious exposures. The current study examines the association between neonatal cytokine profiles and childhood ALL. Methods: Neonatal blood spots of 116 childhood ALL cases and 116 controls living in California were ascertained. 11 cytokines associated with Th1, Th2, and Th17 lymphocytes were measured using a multiplex beadbased assay. Unconditional logistic regression was performed to estimate the odds ratio (OR) measuring the association between neonatal cytokines and ALL adjusted for age, sex, race/ethnicity, and household income. Results: Of the 11 cytokines measured, 5 (IL4, IL6, IL10, IL12, and IL13) were detectable. Except for IL12, the other 4 cytokines were all significantly lower among cases compared to controls. In a multivariable model including the 5 cytokines, only IL10 remained independently associated with childhood ALL with an OR=0.04, 95% confidence interval: 0.01–0.18, comparing the highest tertile to the lowest tertile. Conclusion: IL10 is a key regulator for modulating the intensity and duration of immune responses. The current analysis shows that children with ALL may have a dysregulated immune function present at birth