Differences in MBL levels between juvenile patients newly diagnosed with type 1 diabetes and their healthy siblings

Sildorf, Stine Møller; Eising, Stefanie; Hougaard, David M.; Mortensen, Henrik B.; Skogstrand, Kristin; Pociot, Flemming; Johannesen, Jesper; Svensson, Jannet

doi:10.1016/j.molimm.2014.06.001

Cited by 9 publications

(9 citation statements)

References 21 publications

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“…Regarding MBL, previous reports have shown it to be increased in T1D, specifically when comparing high-producing MBL genotypes (74), or when comparing T1D subjects with at-risk siblings (75). As our study did not involve genetic recognition of MBL genotypes, nor at-risk siblings, we were unable to explore these dimensions.…”

Section: Systemic Endotoxin and Acute Phase Responsesmentioning

confidence: 90%

Confirmation and Identification of Biomarkers Implicating Environmental Triggers in the Pathogenesis of Type 1 Diabetes

et al. 2020

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Multiple environmental triggers have been proposed to explain the increased incidence of type 1 diabetes (T1D). These include viral infections, microbiome disturbances, metabolic disorders, and vitamin D deficiency. Here, we used ELISA to examine blood plasma from juvenile T1D subjects and age-matched controls for the abundance of several circulating factors relevant to these hypotheses. We screened plasma for sCD14, mannose binding lectin (MBL), lipopolysaccharide binding protein (LBP), c-reactive protein (CRP), fatty acid binding protein 2 (FABP2), human growth hormone, leptin, total adiponectin, high molecular weight (HMW) adiponectin, total IgG, total IgA, total IgM, endotoxin core antibodies (EndoCAbs), 25(OH) vitamin D, vitamin D binding protein, IL-7, IL-10, IFN-γ, TNF-α, IL-17A, IL-18, and IL-18BPa. Subjects also were tested for prevalence of antibodies targeting adenovirus, parainfluenza 1/2/3, Coxsackievirus, cytomegalovirus, Epstein-Barr virus viral capsid antigen (EBV VCA), herpes simplex virus 1, and Saccharomyces cerevisiae. Finally, all subjects were screened for presence and abundance of autoantibodies targeting islet cell cytoplasmic proteins (ICA), glutamate decarboxylase 2 (GAD65), zinc transporter 8 (ZNT8), insulinoma antigen 2 (IA-2), tissue transglutaminase, and thyroid peroxidase, while β cell function was gauged by measuring c-peptide levels. We observed few differences between control and T1D subjects. Of these, we found elevated sCD14, IL-18BPa, and FABP2, and reduced total IgM. Female T1D subjects were notably elevated in CRP levels compared to control, while males were similar. T1D subjects also had significantly lower prevalence of EBV VCA antibodies compared to control. Lastly, we observed that c-peptide levels were significantly correlated with leptin levels among controls, but this relationship was not significant among T1D subjects. Alternatively, adiponectin levels were significantly correlated with c-peptide levels among T1D subjects, while controls showed no relationship between these two factors. Among T1D subjects, the highest c-peptide levels were associated with the lowest adiponectin levels, an indication of insulin resistance. In total, from our examination we found limited data that strongly support Harms et al. Confirmation and Identification of Biomarkers any of the hypotheses investigated. Rather, we observed an indication of unexplained monocyte/macrophage activation in T1D subjects judging from elevated levels of sCD14 and IL-18BPa. These observations were partnered with unique associations between adipokines and c-peptide levels among T1D subjects.

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Section: Systemic Endotoxin and Acute Phase Responsesmentioning

confidence: 90%

Confirmation and Identification of Biomarkers Implicating Environmental Triggers in the Pathogenesis of Type 1 Diabetes

et al. 2020

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“…We cannot rule out degradation over time, but it should then be the same for both patients and siblings (sampled in the same period). Different results of the influence of period on the other biomarkers examined in this particular assay are viewed in detail elsewhere . We might have overmatched, which could lead to an underestimation of the true difference between the two groups.…”

Section: Discussionmentioning

confidence: 99%

“…Different results of the influence of period on the other biomarkers examined in this particular assay are viewed in detail elsewhere. [23][24][25][26] We might have overmatched, which could lead to an underestimation of the true difference between the two groups. In the model, patients and siblings coming from the same family is accounted for by a working GEE approach and a benefit of comparing patients with siblings is-to a degree-avoidance of genetic confounding (other than HLA-DQB1 genotypes), which may influence the TREM-1 system.…”

Section: Discussionmentioning

confidence: 99%

Levels of soluble TREM-1 in children with newly diagnosed type 1 diabetes and their siblings without type 1 diabetes: a Danish case-control study

et al. 2016

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“…MBL is an essential component of the innate immune response; the protein is the major recognition molecule of the lectin pathway of complement activation and is activated by binding sugar moieties [ 3 ]. Enhanced glycation results in increased MBL activity and the subsequent activation of the complement system [ 4 ] and high levels of cytokines specific to type 1 diabetes [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous pancreas–kidney transplantation in patients with type 1 diabetes reverses elevated MBL levels in association with MBL2 genotype and VEGF expression

et al. 2016

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Aims/hypothesisHigh levels of circulating mannan-binding lectin (MBL) are associated with the development of diabetic nephropathy and hyperglycaemia-induced vasculopathy. Here, we aimed to assess the effect of glycaemic control on circulating levels of MBL and the relationship of these levels with vascular damage.MethodsWe assessed MBL levels and corresponding MBL2 genotype, together with vascular endothelial growth factor (VEGF) levels as a marker of vascular damage, in type 1 diabetes patients with diabetic nephropathy before and after simultaneous pancreas–kidney (SPK) transplantation. We included diabetic nephropathy patients (n = 21), SPK patients (n = 37), healthy controls (n = 19), type 1 diabetes patients (n = 15) and diabetic nephropathy patients receiving only a kidney transplant (n = 15). Fourteen diabetic nephropathy patients were followed up for 12 months after SPK.ResultsWe found elevated circulating MBL levels in diabetic nephropathy patients, and a trend towards elevated circulating MBL levels in type 1 diabetes patients, compared with healthy control individuals. MBL levels in SPK patients completely normalised and our data indicate that this predominantly occurs in patients with a polymorphism in the MBL2 gene. By contrast, MBL levels in kidney transplant only patients remained elevated, suggesting that glycaemic control but not reversal of renal failure is associated with decreased MBL levels. In line, levels of glucose and HbA1c, but not creatinine levels and estimated GFR, were correlated with MBL levels. VEGF levels were associated with levels of MBL and HbA1c in an MBL-polymorphism-dependent manner.Conclusions/interpretationTaken together, circulating MBL levels are associated with diabetic nephropathy and are dependent on glycaemic control, possibly in an MBL2-genotype-dependent manner.

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Differences in MBL levels between juvenile patients newly diagnosed with type 1 diabetes and their healthy siblings

Cited by 9 publications

References 21 publications

Confirmation and Identification of Biomarkers Implicating Environmental Triggers in the Pathogenesis of Type 1 Diabetes

Confirmation and Identification of Biomarkers Implicating Environmental Triggers in the Pathogenesis of Type 1 Diabetes

Levels of soluble TREM-1 in children with newly diagnosed type 1 diabetes and their siblings without type 1 diabetes: a Danish case-control study

Simultaneous pancreas–kidney transplantation in patients with type 1 diabetes reverses elevated MBL levels in association with MBL2 genotype and VEGF expression

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