Association of Dementia Human Leukocyte Antigen (HLA) Profile with Human Herpes Viruses 3 and 7: An in-silico Investigation
Lisa M. James1,2,3, Spyros A. Charonis1,2, Apostolos P. Georgopoulos1,2,3,4*
1The HLA Research Group, Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, 55417, USA
2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA
3Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA
4Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
Human leukocyte antigen (HLA), the most highly polymorphic region of the human genome, is increasingly recognized as an important genetic contributor to dementia risk and resilience. HLA is involved in protection against foreign antigens including human herpes viruses (HHV), which have been widely implicated in dementia. Here we used an in silico approach1 to determine binding affinities of glycoproteins from 9 human herpes virus (HHV) strains to 113 HLA alleles, and to examine the association of a previously identified HLA-dementia risk profile2 to those affinities. We found a highly significant correlation between high binding affinities of HLA alleles to HHV 3 and 7 and the dementia risk scores of those alleles, such that the higher the estimated binding affinity, the lower the dementia risk score. These findings suggest that protection conferred by HLA alleles may be related to their ability to bind and eliminate HHV3 and HHV7 and point to the possibility that protection against these viruses may reduce dementia incidence.
DOI: 10.29245/2578-3009/2021/3.1218 View / Download Pdf Immunogenetic Epidemiology of Motor Neuron Diseases in 14 Continental Western European Countries
Lisa M. James1,2,3, Apostolos P. Georgopoulos1,2,3,4*
1The HLA Research Group, Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, 55417, USA
2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA
3Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA
4Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
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.
DOI: 10.29245/2578-3009/2021/3.1221 View / Download Pdf Immunogenetic Epidemiology of Type 1 Diabetes in 14 Continental Western European Countries
Lisa M. James1,2,3, Apostolos P. Georgopoulos1,2,3,4*
1The HLA Research Group, Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, 55417, USA
2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA
3Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA
4Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
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.
DOI: 10.29245/2578-3009/2021/3.1219 View / Download Pdf Coenzyme Q10 and Vitamin D Interventions Could Ameliorate COVID-19 Related Cellular Bioenergetic Dysfunction and Cytokine Storms
Darshna Yagnik*
Middlesex University, Department of Natural Sciences, School of Science and Technology, The Burroughs, London, NW4 4BT, UK
The immune response to SARS-CoV-2 varies from asymptomatic or mild symptoms of high temperature, muscle aches and coughs lasting 7 to 14 days to lower respiratory tract infections leading to pneumonia and serious respiratory distress as well as long COVID-19. Complications occur due to an abnormal immune response which involves upregulation of multiple cytokines leading to sustained inflammation which results in the spread of infection to vital organs. The double vaccine roll out has been rapid however vaccine mediated antibodies are not 100% effective against future coronavirus variants which may become increasingly more resistant and easily transmissible to overcome host immunity. Invariably supportive therapies will be needed. Research has shown that coenzyme Q10 and vitamin D deficiencies can have detrimental effects on immune cell defence, function and cytokine secretion promoting inflammation and sepsis especially against microbes. Early interventions including supplementation of these factors could mitigate cellular dysfunction especially in relation to mitochondria bioenergetics and help maintain cell immunity. This is particularly important as chronically ill COVID-19 patients seem to display abnormal immune cell phenotypes in infected organs indicating this could contribute to disease progression. The immune response and proposed roles of Vitamin D and Coenzyme Q10 in COVID-19 are discussed.
DOI: 10.29245/2578-3009/2021/3.1220 View / Download Pdf Inborn Errors of Immunity: What to Look for Beyond Infections
Fernanda Pinto-Mariz*, Ekaterini Goudouris2
IPPMG-Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
Inborn errors of immunity (IEI) are a heterogeneous group of more than 400 diseases, mostly genetically determined, whose main clinical manifestations are severe and / or recurrent infections. Despite the efforts of immunology societies worldwide, this group of diseases remains underdiagnosed. The present review attempts to describe, and call the attention of the physicians, for the infectious and non-infectious manifestations related to IEI. The main clinical manifestations, as well as others that are not so frequent, have been reported in this manuscript. In order to facilitate clinical reasoning, we created a table to illustrated some of them and subdivided the main manifestations into infectious, infectious associated with immune dysregulation, only related to dysregulation and others. The dissemination of knowledge about clinical manifestations, especially non-infectious ones, can contribute to early diagnosis of IEI and, consequently, to the reduction of their morbidity and mortality.
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