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

Maria Vistnes, German Tapia*, Karl Mårild, Øivind Midttun, Per M. Ueland, Marte K. Viken, Per Magnus, Jens P. Berg, Kathleen M. Gillespie, Torild Skrivarhaug, Pål R. Njølstad, Geir Joner, Ketil Størdal, Lars C. Stene

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

3 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Article numbere12802
Number of pages11
JournalAmerican Journal of Reproductive Immunology
Volume79
Issue number3
Early online date20 Dec 2017
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • cord blood
  • cytokine
  • human
  • inflammatory markers
  • Norwegian Mother and Child Cohort Study
  • pregnancy
  • type 1 diabetes

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