Plasma immunological markers in pregnancy and cord blood: a possible link between macrophage chemo-attractants and risk of childhood type 1 diabetes

Problem: Previous studies have suggested that immune perturbations during pregnancy can affect offspring type 1 diabetes (T1D) risk. We aimed to identify immunological markers that could predict offspring T1D or that were linked to T1D risk factors. Method of study: We quantified selected circulating immunological markers in mid-pregnancy (interleukin [IL]-1β, IL-1ra, IL-2Rα, IL-2, -4, -5, -6, -10, -12p70, 13, -17A, GM-CSF, IFN-γ, CXCL10, CCL 2, CCL3, CCL4, TNF) and cord blood plasma (neopterin and kynurenine/tryptophan ratio) in a case-control study with 175 mother/child T1D cases (median age 5.8, range 0.7-13.0 years) and 552 controls. Results: Pre-pregnancy obesity was positively associated with CCL4, CXCL10, kynurenine/tryptophan ratio and neopterin (P <.01). The established T1D SNPs rs1159465 (near IL2RA) and rs75352297 (near CCR2 and CCR3) were positively associated with IL-2Rα and CCL4, respectively (P <.01). There was a borderline association of CCL4 and offspring T1D risk, independent of maternal obesity and genotype. When grouping the immunological markers, there was a borderline association (P =.05) with M1 phenotype and no association between M2-, Th1-, Th2- or Th17 phenotypes and offspring T1D risk. Conclusion: Increased mid-pregnancy CCL4 levels showed borderline associations with increased offspring T1D risk, which may indicate a link between environmental factors in pregnancy and offspring T1D risk.