Maria Vistnes1,2, German Tapia3, Karl Mårild3,4, Øivind Midttun5, Per M Ueland6,7, Marte K Viken8, Per Magnus3, Jens P Berg9,10, Kathleen M Gillespie11, Torild Skrivarhaug10,12, Pål R Njølstad13,14, Geir Joner10,12, Ketil Størdal3,15, Lars C Stene3. 1. Department of Internal Medicine, Diakonhjemmet Hospital, Oslo, Norway. 2. Institute for Experimental Medical Research, Oslo University Hospital, University of Oslo, Oslo, Norway. 3. Norwegian Institute of Public Health, Oslo, Norway. 4. Barbara Davis Center, University of Colorado, Aurora, CO, USA. 5. Bevital AS, Bergen, Norway. 6. Department of Clinical Science, University of Bergen, Bergen, Norway. 7. Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway. 8. Department of Immunology, Rikshospitalet, Oslo University Hospital, Oslo, Norway. 9. Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway. 10. Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 11. Diabetes and Metabolism, School of Clinical Sciences, Southmead Hospital, University of Bristol, Bristol, UK. 12. Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway. 13. KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway. 14. Department of Pediatrics and Adolescent Medicine, Haukeland University Hospital, Bergen, Norway. 15. Pediatric Department, Østfold Hospital Trust, Grålum, Norway.
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.
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.
Authors: German Tapia; Karl Mårild; Sandra R Dahl; Nicolai A Lund-Blix; Marte K Viken; Benedicte A Lie; Pål R Njølstad; Geir Joner; Torild Skrivarhaug; Arieh S Cohen; Ketil Størdal; Lars C Stene Journal: Diabetes Care Date: 2019-01-28 Impact factor: 19.112
Authors: Sari Niinistö; Maija E Miettinen; David Cuthbertson; Jarno Honkanen; Leena Hakola; Reija Autio; Iris Erlund; Petra Arohonka; Arja Vuorela; Taina Härkönen; Heikki Hyöty; Jeffrey P Krischer; Outi Vaarala; Mikael Knip; Suvi M Virtanen Journal: Front Immunol Date: 2022-05-25 Impact factor: 8.786
Authors: Ketil Størdal; Harry J McArdle; Helen Hayes; German Tapia; Marte K Viken; Nicolai A Lund-Blix; Margaretha Haugen; Geir Joner; Torild Skrivarhaug; Karl Mårild; Pål R Njølstad; Merete Eggesbø; Siddhartha Mandal; Christian M Page; Stephanie J London; Benedicte A Lie; Lars C Stene Journal: Sci Rep Date: 2018-06-13 Impact factor: 4.379
Authors: German Tapia; Tommi Suvitaival; Linda Ahonen; Nicolai A Lund-Blix; Pål R Njølstad; Geir Joner; Torild Skrivarhaug; Cristina Legido-Quigley; Ketil Størdal; Lars C Stene Journal: J Clin Endocrinol Metab Date: 2021-09-27 Impact factor: 5.958