A proinflammatory CD4+ T cell phenotype in gestational diabetes mellitus
Numerous adaptations of the maternal immune system are necessary during pregnancy to maintain immunological tolerance to the semi-allogeneic fetus. Several complications of pregnancy have been associated with dysregulation of these adaptive mechanisms. While gestational diabetes mellitus (GDM) has been associated with upregulation of circulating inflammatory factors linked to innate immunity, polarisation of the adaptive immune system has not been extensively characterised in this condition. We aimed to characterise pro- and anti-inflammatory CD4+ (T helper [Th]) T cell subsets in women with GDM vs women without GDM (of similar BMI), during and after pregnancy, and examine the relationship between CD4+ subsets and severity of GDM.
This is a prospective longitudinal case–control study of 55 women with GDM (cases) and 65 women without GDM (controls) at a tertiary maternity hospital. Quantification of proinflammatory (Th17, Th17.1, Th1) and anti-inflammatory (regulatory T cell [Treg]) CD4+ T cell subsets was performed on peripheral blood at 37 weeks gestation and 7 weeks postpartum, and correlated with clinical characteristics and measures of blood glucose.
Women with GDM had a significantly greater percentage of Th17 (median 2.49% [interquartile range 1.62–4.60] vs 1.85% [1.13–2.98], p = 0.012) and Th17.1 (3.06% [1.30–4.33] vs 1.55% [0.65–3.13], p = 0.006) cells compared with the control group of women without GDM. Women with GDM also had higher proinflammatory cell ratios (Th17:Treg, Th17.1:Treg and Th1:Treg) in pregnancy compared with the control group of women without GDM. In the control group, there was a statistically significant independent association between 1 h glucose levels in the GTT and Th17 cell percentages, and also between 2 h glucose levels and percentage of Th17 cells. The percentage of Th17 cells and the Th17:Treg ratio declined significantly after delivery in women with GDM, whereas this was not the case with the control group of women. Nevertheless, a milder inflammatory phenotype persisted after delivery (higher Th17:Treg ratio) in women with GDM vs women without.
Dysregulation of adaptive immunity supports a novel paradigm of GDM that extends beyond hyperglycaemia and altered innate immunity.
KeywordsAdaptive immunity Diabetes Gestational diabetes mellitus Inflammation Pregnancy T cells Th17
Glucose challenge test
Gestational diabetes mellitus
Large for gestational age
Peripheral blood mononuclear cell
Small for gestational age
Regulatory T cell
The authors would like to thank S. L. Lau (Department of Diabetes and Endocrinology, Westmead Hospital, Westmead, NSW, Australia) for reviewing the manuscript and P.-A. Sierro (Les Rocailles, Heremence, Switzerland) for technical assistance.
AS acquired, analysed and interpreted data and contributed to drafting the article. YC acquired, analysed and interpreted the data and revised the article. AF, MB, CW, YFC, WH, HW and PB acquired and/or interpreted data and revised the manuscript. UP interpreted data, was involved in study design and revised the article. FS and SML designed and supervised the study, acquired and analysed the data and wrote the article. All authors approved the final version of the article. FS and SML are responsible for the integrity of the work as a whole.
This study was supported by an Australasian Diabetes in Pregnancy Society research grant and a Prince of Wales Hospital Foundation grant.
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
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