Immunogenetic Epidemiology of Type 1 Diabetes in 14 Continental Western European Countries

2021 ◽  
Vol 5 (3) ◽  
pp. 29-35
Author(s):  
Lisa M. James ◽  
Apostolos P. Georgopoulos
Keyword(s):  
Type 1 Diabetes ◽  
Pancreatic Beta Cells ◽  
Human Leukocyte ◽  
Population Level ◽  
Hla Class I ◽  
European Countries ◽  
Pathogen Elimination ◽  
Western European

Human leukocyte antigen (HLA) is widely recognized to influence individual Type 1 diabetes (T1D) risk. Here we utilized an immunogenetic epidemiological approach to evaluate the influence of HLA on T1D at the population level. Specifically, we evaluated the correlations between the population frequencies of 127 HLA Class I and II alleles and the population prevalence of T1D in 14 Continental Western European countries to identify a population-level HLA profile for T1D. The results of these analyses generally corroborated prior findings regarding the influence of HLA on T1D risk and protection and revealed several novel HLA-T1D associations. The findings, discussed within the context of the role of HLA in pathogen elimination and autoimmunity, point to a contributory role of exposure to pathogens in the absence of protective HLA in underlying the autoimmune destruction of pancreatic beta cells in T1D.

scholarly journals Immunogenetic Epidemiology of Multiple Sclerosis in 14 Continental Western European Countries

2021 ◽  
Vol 5 (2) ◽  
pp. 40-46
Author(s):  
Lisa M. James ◽  
Apostolos P. Georgopoulos
Keyword(s):  
Multiple Sclerosis ◽  
Human Leukocyte ◽  
Hla Class I ◽  
European Countries ◽  
Class I ◽  
Hla Alleles ◽  
Susceptibility Effect ◽  
Pathogen Elimination ◽  
Western European

Human leukocyte antigen (HLA), a system involved in immune response to foreign antigens and in autoimmunity, has been strongly implicated in multiple sclerosis (MS). Prior research has shown that HLA DRB1*15:01 exerts the strongest susceptibility effect, although other HLA alleles have been implicated in both susceptibility to, and protection against, MS. Here we utilized an immunogenetic epidemiological approach to evaluate correlations between the population frequencies of 127 HLA Class I and II alleles and the population prevalence of MS in 14 Continental Western European countries to identify an HLA profile for MS. The results of these analyses, which largely corroborated prior findings and revealed several novel and highly robust HLA associations with MS, revealed a larger number of protective HLA alleles than susceptibility alleles, particularly for HLA Class I. Given the role of HLA in pathogen elimination and autoimmunity, these findings point to a contributory role of exposure to pathogens in the absence of protective HLA in underlying the inflammation and autoimmunity associated with MS.

scholarly journals Immunogenetic Epidemiology of Motor Neuron Diseases in 14 Continental Western European Countries

2021 ◽  
Vol 5 (3) ◽  
pp. 22-28
Author(s):  
Lisa M. James ◽  
Apostolos P. Georgopoulos
Keyword(s):  
Motor Neuron ◽  
Human Leukocyte ◽  
Population Level ◽  
Hla Class I ◽  
European Countries ◽  
Class I ◽  
Motor Neuron Diseases ◽  
Population Prevalence ◽  
Susceptibility Effects ◽  
Western European

Very few studies have evaluated associations of human leukocyte antigen (HLA) with motor neuron diseases (MND). Using an immunogenetic epidemiological approach, we identified a population-level HLA profile for MND by evaluating the correlations between the population frequencies of 127 HLA Class I and II alleles and the population prevalence of MND in 14 Continental Western European countries. The results demonstrated that significantly more HLA alleles, particularly for Class I, were negatively associated with the population prevalence of MND, suggesting a preponderance of protective vs susceptibility effects. The findings add to the limited literature implicating HLA in MND and considering the role of HLA in immune system responses to pathogens, suggest a potential influence of pathogens in MND.

scholarly journals Juxtaposition of Coeliac Disease and Type 1 Diabetes; the Role of Shared Non-Human Leukocyte Antigen Loci

2018 ◽  
Vol 3 (1) ◽  
pp. 1-8
Author(s):  
Iraj Shahramian ◽  
Hossein Shahdadi ◽  
Ali Bazi ◽  
Nosratollah Masinaeinejad ◽  
Mojtaba Delaramnasab
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Human Leukocyte Antigen ◽  
Coeliac Disease ◽  
Adaptor Protein ◽  
Human Leukocyte ◽  
Substantial Impact ◽  
Leukocyte Antigen

Although extensive studies have been performed to explore the role of various alleles within the human leukocyte antigen (HLA) in susceptibility to coeliac disease (CD) and type 1 diabetes (T1D), less attention has been dedicated to the role of shred non-HLA loci. In present report, we have provided a review on the role of genetic variants in seven shared non-HLA loci in determination the risk of either CD or T1D. The literature search was done on the Web of Knowledge, PubMed, and Scopus databases using keywords of polymorphism, coeliac disease, and type 1 diabetes. The literature published within 2000-2017 were recruited. Seven discussed shared loci between CD and T1D were those resided within cytotoxic T-lymphocyte associated protein 4 (CTL4), regulator of G protein signaling (RGS1), SH2B adaptor protein (SH2B3), T cell activation Rho GTPase activating protein (TAGAP), interleukin 18 receptor accessory protein (IL18RAP), protein tyrosine phosphatase, non-receptor type (PTPN2), and C-C motif chemokine receptor (CCR5). Interaction between polymorphisms of these genes seems to exert a substantial impact on determination the risk of CD and T1D in context of each other. Polymorphisms residing in these loci can exert synergistic or opposing effects toward either protection or predisposition to CD and T1D. The majority of these polymorphisms affect the function of cytokine signaling or T cell activating pathways. The net outcome deems to be delineated by a complex interaction between these adaptor arms, as well as the modulatory effects of other components of immune system, in particular HLA alleles.

scholarly journals Impaired Innate Immunity in Pediatric Patients Type 1 Diabetes—Focus on Toll-like Receptors Expression

2021 ◽  
Vol 22 (22) ◽  
pp. 12135
Author(s):  
Katarzyna Kurianowicz ◽  
Maria Klatka ◽  
Agnieszka Polak ◽  
Anna Hymos ◽  
Dominika Bębnowska ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cd8 T Cells ◽  
Pancreatic Beta Cells ◽  
Pediatric Patients ◽  
Early Stage ◽  
Newly Diagnosed ◽  
The Relationship ◽  
B And T Lymphocytes

Type 1 diabetes (DM1) is classified as an autoimmune disease. An uncontrolled response of B and T lymphocytes to the body’s own tissues develops in the absence of immune tolerance. The main aim of the study was to evaluate the effect of the duration of type 1 diabetes in children on the expression of TLR receptors and the relationship with the parameters of glycemic control in patients. As a result, we showed significant differences in the level of TLR2, TLR4 and TLR9 expression in patients with DM1 in the early stage of the disease and treated chronically compared to the healthy group. Additionally, in this study, we found that the numbers of CD19+ B cells, CD3+ CD4+, CD3+ CD8+ T cells and NK cells are different for newly diagnosed DM1 individuals, patients receiving chronic treatment and for healthy controls, indicating an important role of these cells in killing pancreatic beta cells. Moreover, higher levels of IL-10 in patients with newly diagnosed DM1 have also been found, confirming the reports found in the literature.

scholarly journals Enteroviral Pathogenesis of Type 1 Diabetes: The Role of Natural Killer Cells

2020 ◽  
Vol 8 (7) ◽  
pp. 989 ◽  
Author(s):  
Magloire Pandoua Nekoua ◽  
Arthur Dechaumes ◽  
Famara Sane ◽  
Enagnon Kazali Alidjinou ◽  
Kabirou Moutairou ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Nk Cells ◽  
Pancreatic Beta Cells ◽  
Cytotoxic T Cells ◽  
Hla Class I ◽  
Surface Expression ◽  
Cytolytic Activity ◽  
Cell Surface Expression ◽  
Group B

Enteroviruses, especially group B coxsackieviruses (CV-B), have been associated with the development of chronic diseases such as type 1 diabetes (T1D). The pathological mechanisms that trigger virus-induced autoimmunity against islet antigens in T1D are not fully elucidated. Animal and human studies suggest that NK cells response to CV-B infection play a crucial role in the enteroviral pathogenesis of T1D. Indeed, CV-B-infected cells can escape from cytotoxic T cells recognition and destruction by inhibition of cell surface expression of HLA class I antigen through non-structural viral proteins, but they can nevertheless be killed by NK cells. Cytolytic activity of NK cells towards pancreatic beta cells persistently-infected with CV-B has been reported and defective viral clearance by NK cells of patients with T1D has been suggested as a mechanism leading to persistence of CV-B and triggering autoimmunity reported in these patients. The knowledge about host antiviral defense against CV-B infection is not only crucial to understand the susceptibility to virus-induced T1D but could also contribute to the design of new preventive or therapeutic approaches for individuals at risk for T1D or newly diagnosed patients.

scholarly journals The role of apoptosis in pathogenesis of type 1 diabetes mellitus

2010 ◽  
Vol 13 (1) ◽  
pp. 45-49
Author(s):  
Elena Vladimirovna Pekareva ◽  
Tatiana Vasil'evna Nikonova ◽  
Olga Mikhailovna Smirnova
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Beta Cell ◽  
Type 1 Diabetes Mellitus ◽  
Beta Cells ◽  
Cell Apoptosis ◽  
Pancreatic Beta Cells ◽  
Beta Cell Apoptosis

Type 1 diabetes mellitus (DM1) is known to be associated with progressive destruction of pancreatic beta-cells. Apoptosis plays the key role in this destructiveprocess. The paper focuses on major mechanisms underlying activation of beta-cell apoptosis and its role in regulation of immune processes inpatients with DM1.

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