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Immune Profiles in Childhood Leukemia: Investigating Infection Susceptibility and Immune System Alterations

Explore the relationship between childhood leukemia, infections, and immune profiles at birth. Investigate the potential immune system alterations in children with leukemia and their susceptibility to infections.

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Immune Profiles in Childhood Leukemia: Investigating Infection Susceptibility and Immune System Alterations

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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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