Early-pregnancy cytokines in mothers to children developing multiple, persistent islet autoantibodies, type 1 diabetes, or both before 7 years of age

Abstract

Problem: Increased levels of serum cytokines in early pregnancy may increase the risk of type 1 diabetes in the offspring.

Method of study: Early-pregnancy (between 10 and 16 gestational weeks) serum samples from non-diabetic index mothers (n = 48) of children who developed islet autoimmunity, type 1 diabetes, or both before 7 years of age were analyzed for IFN-γ, IL-10, IL-12, IL-13, IL-1β, IL-2, IL-4, IL-5, CXCL8, and TNF. Control mothers (n = 93) were matched for age, sampling date, and HLA-DQ genotypes.

Results: IFN-γ (P = 0.02) and IL-1β (P = 0.04) were elevated in the index mothers. All cytokines except IL-4 were highly correlated (P < 0.0001). IFN-γ [OR 1.39 (1.04, 1.85), P = 0.026] and possibly IL-2 [OR 1.21 (0.99, 1.48), P = 0.057] in early pregnancy were associated with an increased risk of multiple, persistent islet autoantibodies, type 1 diabetes, or both before 7 years of age in the offspring. However, the statistical significance for IL-2 was lost in the logistic regression when adjusted for gestational length at delivery and parity.

Conclusion: Increased Th1 cytokine levels during early pregnancy might contribute to an increased risk of islet autoimmunity, type 1 diabetes, or both in the offspring.