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Outline. Children who get leukemia are exposed to fewer infections, but when they do get infections, are more susceptible to illness. Are children who contract leukemia born with altered “ at-risk ” immune systems?

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Outline

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  1. Outline Children who get leukemia are exposed to fewer infections, but when they do get infections, are more susceptible to illness. • Are children who contract leukemia born with altered “at-risk” immune systems? Infection can be a precipitating event in the year prior to leukemia, but no infection has been found in leukemia cells. • Is there a “hit and run” mechanism in leukemogenesis?

  2. Day care Attendance/Social Activity (ever/never) & Childhood ALL Combined OR = 0.77 95% CI = 0.66-0.88 Urayama et al., 2010

  3. Uk childhood cancer study findings “Physician diagnosed” infection is a risk factor, not protective factor JNCI 2007 Roman et al.

  4. Guthrie Cards Sample of blood taken immediately after birth (1-3 days) Available for all children born in California Used to trace back leukemia origin to fetal period

  5. Cytokine profiles at birth Is there a immune profile at birth different between cases and controls? 116 leukemia (ALL) case Guthrie cards, 116 birthdate, gender, and ethnicity-matched controls Protein extracts from cards, analyzed by Luminex Th1 IL2, IL12(p70), IFN-γ, TNF-α Th2: IL4, IL5, IL10, IL13 Th17: IL17, IL6 Other: GM-CSF Only 5 were detectable: IL4, IL6, IL10, IL12, IL13

  6. Correlation between cytokines Controls Cases

  7. Cytokine relation to leukemia status

  8. IL10 Produced by Monocytes, Regulatory T-cells, and B-1 cells Suppresses inflammatory Th1-type responses and enhances B-cell development and function Critical role in pregnancy – suppression of the immune rejection of the fetus New subtype of B-1 cells: “Regulatory B10 cells” – 20% of B-cells at birth (CD1dhiCD5+CD19hi) – predominant source of B-cell IL10 at birth

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