HLA, infections and inflammation in early stages of atherosclerosis in children with type 1 diabetes

Odermarsky, Michal; Pesonen, Erkki; Sorsa, Timo; Lernmark, Åke; Pussinen, Pirkko J.; Liuba, Petru

doi:10.1007/s00592-017-1063-1

Cited by 5 publications

(5 citation statements)

References 35 publications

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“…Obesity and T2D are characterized by a state of systemic chronic low-grade inflammation, that triggers a vicious circle involving insulin resistance, oxidative stress and endothelial dysfunction and lays the basis for early and accelerated atherosclerosis [ 46 ]. A low-grade inflammation is also observed in lean children with T1D, while increased levels of pro-inflammatory cytokines are described, either in T1D or T2D [ 48 , 49 ]. Continuous systemic chronic inflammation from childhood accelerates plaque formation and contributes to its growth [ 48 ].…”

Section: Inflammation In Children and Adolescents With Diabetesmentioning

confidence: 99%

“…A low-grade inflammation is also observed in lean children with T1D, while increased levels of pro-inflammatory cytokines are described, either in T1D or T2D [ 48 , 49 ]. Continuous systemic chronic inflammation from childhood accelerates plaque formation and contributes to its growth [ 48 ]. Nearly 700 adolescents aged between 10 and 17 years who had a recent diagnosis of T2D were studied, and a detrimental inflammatory profile that worsened over time was shown [ 50 ].…”

Section: Inflammation In Children and Adolescents With Diabetesmentioning

confidence: 99%

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The Impact of Diabetes Mellitus on Cardiovascular Risk Onset in Children and Adolescents

Pastore

Bolla

Montefusco

et al. 2020

IJMS

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The prevalence of diabetes mellitus is rising among children and adolescents worldwide. Cardiovascular diseases are the main cause of morbidity and mortality in diabetic patients. We review the impact of diabetes on establishing, during childhood and adolescence, the premises for cardiovascular diseases later in life. Interestingly, it seems that hyperglycemia is not the only factor that establishes an increased cardiovascular risk in adolescence. Other factors have been recognized to play a role in triggering the onset of latent cardiovascular diseases in the pediatric population. Among these cardiovascular risk factors, some are modifiable: glucose variability, hypoglycemia, obesity, insulin resistance, waist circumference, hypertension, dyslipidemia, smoking alcohol, microalbuminuria and smoking. Others are unmodifiable, such as diabetes duration and family history. Among the etiological factors, subclinical endothelial dysfunction represents one of the earliest key players of atherosclerosis and it can be detected during early ages in patients with diabetes. A better assessment of cardiovascular risk in pediatric population still represents a challenge for clinicians, and thus further efforts are required to properly identify and treat pediatric patients who may suffer from cardiovascular disease later in early adulthood.

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Section: Inflammation In Children and Adolescents With Diabetesmentioning

confidence: 99%

Section: Inflammation In Children and Adolescents With Diabetesmentioning

confidence: 99%

The Impact of Diabetes Mellitus on Cardiovascular Risk Onset in Children and Adolescents

Pastore

Bolla

Montefusco

et al. 2020

IJMS

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“…In addition to HLA‐conferred disease risk, lifestyle and environmental factors (eg, in the form of early childhood respiratory infections) are associated with an increased risk for the development of islet autoimmunity and T1D. Diabetic children with the DQ2/DQ8 risk haplotype have been shown to have worse endothelial cell dysfunction and atherosclerotic changes in vasculature after acute respiratory infections than healthy children indicating interplay between HLA and infections on the wall of blood vessels . In addition, class I HLA genes have been associated with T1D.…”

Section: Hla and Disease Associationsmentioning

confidence: 99%

“…Diabetic children with the DQ2/DQ8 risk haplotype have been shown to have worse endothelial cell dysfunction and atherosclerotic changes in vasculature after acute respiratory infections than healthy children indicating interplay between HLA and infections on the wall of blood vessels. 75 In addition, class I HLA genes have been associated with T1D. Young age, autoantibody profiles, and higher prevalence of non-HLA FUT2 (fucosyltransferase 2) SNPs with predisposing HLA-risk genes may characterize rapid disease progression in children.…”

Section: Hla and Disease Associationsmentioning

confidence: 99%

The complexity and diversity of major histocompatibility complex challenge disease association studies

Lokki

Paakkanen

2018

HLA

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The major histocompatibility complex (MHC; 6p21.3) contains the most polymorphic genes, the most gene dense parts, and the highest diversity of functional gene clusters of the human genome. The clusters form haplotypes, which differ in linkage disequilibrium and show large variations in strength and extent between populations. Haplotype cis‐ and trans‐expression quantitative trait loci have increased the knowledge of regulatory interactions between multiple MHC genes. The detailed haplotype data offer a reference for future studies in immune‐mediated diseases and may unravel disease associations in conditions traditionally considered not to be immunologic. This article aims to describe the structural and functional variations of the MHC genes and haplotypes and their role on selected immune‐mediated diseases. In immune‐/inflammation‐mediated complex diseases, hundreds of common variants influence the development of the disease trait, but the individual variants have small effects on the disease phenotypes as seen in genome‐wide association studies. The genetic influence may still be significant on the cellular or molecular level. Nonetheless, the HLA alone is not sufficient as a susceptible genetic background to deduce the disease. For a comprehensive insight of the disease mechanisms, both immunological and genome assays methods are required.

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“…In addition to periodontitis, recent studies have shown aMMP-8 to be associated with chronic inflammation and inflammatory diseases including obesity, rheumatoid arthritis and cardiovascular diseases (Äyräväinen et al, 2018;Lauhio et al, 2016;Tuomainen et al, 2014). Furthermore, aMMP-8 has been observed to be associated with an elevated C-reactive protein level among subjects with the diabetes risk genotype HLA-DQ2/8 (Odermarsky et al, 2018).…”

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confidence: 99%

Human leukocyte antigens are associated with salivary level of active MMP‐8

Mauramo

Sorsa

et al. 2021

Clinical & Exp Dental Res

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Objectives: This case control study examined the associations of HLA antigens and periodontitis with the salivary level of active .Materials and Methods: A total of 202 subjects, registered as Swiss bone marrow donors, participated in the study. HLA-A, -B, and -C types were determined by serology or PCR. Saliva samples were collected from subjects, followed by a periodontal examination. The salivary level of aMMP-8 was determined with immunofluorometric assay. Results:The mean salivary level of aMMP-8 was directly comparable to the grade of periodontitis and increased from healthy to mild/moderate to severe (125.0 ± 132.1, 200.6 ± 170.2, 290.1 ± 202.3 ng/ml; p < 0.001 between each group, respectively).The only association between the HLA types and the salivary level of aMMP-8 was observed in subjects with HLA-A11. Subjects with healthy periodontium and HLA-A11 had a lower level of aMMP-8 (49.2 ± 32.5 ng/ml) compared with subjects without HLA-A11 (123.6 ± 119.2; p = 0.048). Among subjects with periodontitis, a higher level of aMMP-8 (394.2 ± 255.6 ng/ml) was observed in subjects with HLA-A11 compared with subjects without HLA-A11 (201.1 ± 146.1 ng/ml; p < 0.002). This finding was statistically significant also after adjusting for sex, age, smoking, tooth brushing and the number of medications (p < 0.05).Conclusions: HLA-A11 is associated with the salivary level of aMMP-8 which contributes to the subject's immune and inflammatory response in periodontium.

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HLA, infections and inflammation in early stages of atherosclerosis in children with type 1 diabetes

Cited by 5 publications

References 35 publications

The Impact of Diabetes Mellitus on Cardiovascular Risk Onset in Children and Adolescents

The Impact of Diabetes Mellitus on Cardiovascular Risk Onset in Children and Adolescents

The complexity and diversity of major histocompatibility complex challenge disease association studies

Human leukocyte antigens are associated with salivary level of active MMP‐8

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