Influence of Maternal Hyperglycaemia on Cord Blood Mononuclear Cells in Response to Diabetes‐associated Autoantigens

Abstract

Perfect maternal diabetes compensation is crucial for the outcome of the baby. However, little is known how hyperglycaemia influences the specific immune response. Furthermore, babies of type 1 diabetes (T1D) mothers have less risk of development T1D than babies with a T1D father. This study aimed to analyze the effect of maternal hyperglycaemia on newborns with focus on the response to diabetes‐associated autoantigens. Populations: (1) Newborns of T1D mothers split into groups according to maternal diabetes compensation during the 3rd trimester: perfect (n = 15) or acceptable (n = 25) compensation. (2) newborns with T1D father (n = 12) (3) newborns with a mother treated for either gestational or type 2 diabetes (n = 10) (4) control newborns (n = 25). Spontaneous as well as diabetes‐associated autoantigen‐stimulated production of 23 cytokines and chemokines were tested using protein microarray. In addition, the influence of glucose on cytokine and chemokine responsiveness was analyzed in vitro. The study groups differed in their spontaneous as well as stimulated cytokine and chemokine spectra. A prominent Th1 response (high IFN‐gamma) from autoantigen stimulation was observed especially in babies of T1D fathers (P = 0.001) and also in mothers with perfect diabetes compensation during the 3rd trimester (P = 0.016) in comparison with control newborns. By contrast, cord blood mononuclear cells cultivated in vitro in high glucose concentration decreased the diabetogenic stimulated Th1 cytokine response. Maternal ‘sweet’ as well as ‘autoimmune environment’ may both lead to lower occurrence of T1D within their offspring. Further studies will reveal the exact immunological mechanism of this observation.

Identification and validation of genes involved in gastric tumorigenesis

“…Custom antibody arrays Quantibody ™ array (Catalogue number: QAA-CUST) based on a multiplex ELISA system for quantitative measurement of multiple proteins purchased from Ray Biotech, Inc, USA was used to study protein expression levels in gastric tissues and plasma samples [ 22 , 23 ]. The following genes (CXCL5/ENA-78, CXCL8/IL8, CXCL10/IP10, CXCL9/MIG, CCL3/MIP-1α, CCL15/MIP-1δ, EpCAM, MMP3, SPP1/OPN, TIMP1, Adipsin/CFD, CCL4/MIP-1β, CCL20/MIP-3α, PDGFR-B and IGFBP-3) found to be overexpressed in gastric cancers relative to PN and AN (with the exception of CFD/Adipsin which was overexpressed in PN relative to gastric cancers and AN) were studied for their protein levels in tumour, corresponding PN and in AN tissues.…”

Not Only Glycaemic But Also Other Metabolic Factors Affect T Regulatory Cell Counts and Proinflammatory Cytokine Levels in Women with Type 1 Diabetes

“…Notably, we evaluated the effect of maternal glycaemic control on the cytokine profile of newborn cord blood mononuclear cells (CBMCs). The result of this study demonstrated that nonstimulated or diabetogenic autoantigen-stimulated newborn CBMCs of T1D mothers with poor glycaemic control exhibited lower cytokine and chemokine production compared to those of mothers with well-stabilized glycaemic control [5]. Consistent with this conclusion was the demonstration that high glucose concentration in culture media that mimicked “hyperglycaemia” also dampened the production of cytokines and chemokines [5].…”

“…The result of this study demonstrated that nonstimulated or diabetogenic autoantigen-stimulated newborn CBMCs of T1D mothers with poor glycaemic control exhibited lower cytokine and chemokine production compared to those of mothers with well-stabilized glycaemic control [5]. Consistent with this conclusion was the demonstration that high glucose concentration in culture media that mimicked “hyperglycaemia” also dampened the production of cytokines and chemokines [5]. This study not only contributed to our increasing knowledge on foetal cell reprogramming and the importance of an intrauterine environment for the future health status of the child [6], but it also raised important questions concerning the impact of other metabolic disturbances on the immune system.…”

Autoimmunity: limited progress for the patient, despite decades of research

“…For example, a similar search in MedLine indicated that 40 papers on autoimmunity were published over the past two and one‐half years [11–50]. While 19 of these deal primarily with general immunology [11–26] genetics [27] and technologies [28, 29], the remaining 21 papers [30–50] focus on specific autoimmune diseases. Not surprising, the more popular topics have been multiple sclerosis/experimental autoimmune encephalomyelitis (six manuscripts) [30–35] diabetes/Addison’s disease (four manuscripts) [36–39] and rheumatic diseases/collagen‐induced arthritis (four manuscripts) [40–43].…”

“…While 19 of these deal primarily with general immunology [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] genetics [27] and technologies [28,29], the remaining 21 papers focus on specific autoimmune diseases. Not surprising, the more popular topics have been multiple sclerosis ⁄ experimental autoimmune encephalomyelitis (six manuscripts) [30][31][32][33][34][35] diabetes ⁄ Addison's disease (four manuscripts) [36][37][38][39] and rheumatic diseases ⁄ collagen-induced arthritis (four manuscripts) [40][41][42][43]. Which of these manuscripts have or will make a difference for the autoimmune patient?…”