Volume Articles

Immunogenetic Epidemiology of Dementia and Parkinson’s Disease in 14 Continental European Countries: Shared Human Leukocyte Antigen (HLA) Profiles

Lisa M. James^1,2,3, Apostolos P. Georgopoulos^1,2,3,4*

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), which is critically involved in immune response to foreign antigens and in autoimmunity, has been implicated in dementia and Parkinson’s disease. Here we report on the correlations between the population frequencies of 127 HLA Class I and II alleles and the population prevalence of dementia and Parkinson’s disease in 14 Continental Western European countries, extending previous work^1,2. We used these correlations to construct and compare HLA profiles for each disease³. We found that (a) the HLA profiles of the two diseases were significantly correlated across both HLA Class I and Class II alleles, (b) negative (“protective”) HLA-disease correlations did not differ significantly for either HLA class, but (c) positive (“susceptibility”) HLA-disease correlations were significantly higher in dementia than in Parkinson’s disease for both HLA classes of alleles. These findings indicate that (a) dementia and Parkinson’s disease share immunogenetic HLA-related mechanisms, (b) HLA-related protective mechanisms (presumably against pathogens) do not differ between the two diseases, but (c) HLA-related susceptibility mechanisms (presumably underlying autoimmunity) are significantly stronger in dementia than in Parkinson’s disease.

SARS-CoV-2: Insights from the Immunopathogenesis and Current Clinical Diagnosis and Therapeutic Strategies

Shruti Sharma^1*, Ujjawal Sharma^2#, Anupama Chaudhary³, Manisha Naithani⁴, Priyanka Naithani⁵, Saurabh Prashar², Bunty Sharma⁶, Pramod Kumar Nagar⁷, Prudhvi Lal Bhukya⁸, Unnati Bhalerao⁸, Meenakshi Singh⁹, Manjita Srivastava⁸, Muneesh Kumar Barman¹⁰, Sampan Attri², Jitender Gairolla^2,11# 

¹Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

²Department of Community Medicine and School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India

³Orinin BioSystems, Karnal, India

⁴Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, India

⁵Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

⁶Chitkara School of Health Sciences, Chitkara University, Punjab, India

⁷Hematology Oncology Unit, Advance Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, Chandigarh, India

⁸National Institute of Virology, Pune, India

⁹Transplant Immunology and Immunogenetics Lab (HLA), ACTREC, Tata Memorial Centre

¹⁰Laboratory for HIV Research, National Centre for Cell Sciences, Pune-India

¹¹Department of Microbiology, All India Institute of Medical Sciences, Rishikesh, India

The global public health scenario is worsening gradually as the confirmed cases of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections are incessantly escalating with every passing day. The pathological condition caused by SARS-CoV-2 is termed as Coronavirus disease 2019 (COVID-19). The understanding of SARS-CoV-2 transmission dynamics, immunopathogenesis, and the need for early-stage diagnosis and the effective therapeutic regime are the few immediate challenges faced by healthcare professionals worldwide. More specifically, the role of SARS-CoV-2 in the host’s immunopathogenesis response is crucial to determine the disease severity and its clinical outcome in COVID-19 patients. In the present review, we provide insights into the SARS-CoV-2 pathology, host immune responses including innate, cellular, and humoral responses, and immunomodulatory functions of SARS-CoV-2 including cytokine storm and immune evasion. We also shed light upon the present clinical and laboratory-based applications enrolled in the SARS-CoV-2 diagnosis. Taking into consideration the pathogenesis and SARS-CoV-2 immune function, in the present review, we finally provide succinct insights into the SARS-CoV-2 transmission dynamics, immunopathogenesis, with the assessment of the current diagnostic and preventive/ therapeutic strategies.

Curing Cancer with Nanotherapy Continues to be an Elusive Goal

Priyanka Ray

Department of Chemical, Biochemical and Environmental Engineering, University of Maryland, Baltimore County, Baltimore MD, 21250, USA

Importance of Interkingdom Interactions Among Oral Microbiome Towards Caries Development – A Review

Kalpana Balakrishnan^{1, 4}, Divya Sivanesan¹, Gaanappriya Mohan⁴, Sachin S Gunthe^2,3, Rama S Verma^1*

¹Department of Biotechnology, Indian Institute of Technology Madras, Chennai

²Department of Civil Engineering, Indian Institute of Technology Madras, Chennai

³Laboratory of Atmospheric and Climate Sciences, Institute of Technology Madras, Chennai

⁴Department of Biotechnology, K. S. Rangasamy College of Technology, Namakkal Tamil Nadu, India

The human microbiome plays a crucial role in health and disease conditions. These microbiomes constitute a structured, coordinated microbial network throughout the human body. The oral cavity harbors one of the extensively diverse bacteria in the human system. Although many studies emphasize bacteriome and its interaction with the host system, very little attention is given to candidate phyla radiation (CPR), fungal components, and its interkingdom interaction in the oral microecology even with advanced techniques. The interkingdom interactions among caries causing microbes trigger the pathogenesis of bacterial diseases and cause ecological shifts and affect the host system. Studying the complex relations among the diverse oral microbiome and its host, especially CPR phyla and fungi, would give a holistic view of the caries etiology. This review provides evidence on the interkingdom interaction that establishes a complex community that could help predict future oral and systemic diseases.

Immunogenetic Epidemiology of Multiple Sclerosis in 14 Continental Western European Countries

Lisa M. James^1,2,3, Apostolos P. Georgopoulos^1,2,3,4*

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), 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.

Association of Lupus Anticoagulant with Brain Atrophy in Gulf War Illness (GWI)

Lisa M. James^1,2,3, Peka Christova^1,2, Rachel A. Johnson¹, Brian E. Engdahl^1,2,4, Scott M. Lewis^1,5, Adam F. Carpenter^1,5, Apostolos P. Georgopoulos^1,2,3,5*

¹Brain 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 Psychology, University of Minnesota Medical School, Minneapolis, MN 55455, USA

⁵Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA

Separate lines of research have documented brain atrophy and evidence of autoimmune mechanisms in Gulf War Illness (GWI), including the presence of lupus anticoagulant (LAC), in veterans with GWI. Here we evaluated the possible association of LAC and brain volume in veterans with GWI. The presence of LAC was determined using Silica Clotting Time and dilute Russell’s Viper Venom Time assays. MRI data was acquired using a Philips 3T MR scanner from which total gray matter, total cortical gray matter, total subcortical gray matter, and total cerebral white matter were derived. The results demonstrated a statistically significant reduction of brain volume in all regions tested in GWI veterans with positive LAC, as compared to those without LAC. These findings add to the literature implicating autoimmune mechanisms in GWI and point to the presence of prothrombotic antiphospholipid antibodies as contributing to brain atrophy in GWI.

HPV Catch-up Vaccination is Effective but Cervical Screening Should Continue

Nick F. Hallam^*

Colposcopy Clinic, Women's Outpatients, Cumberland Infirmary, Carlisle, England, United Kingdom

This short communication reports additional research that extends the previously published article - Commentary: HPV Catch-Up Vaccination Reduces the Prevalence of HPV 16 and 18 Infections and Cervical Disease: A Retrospective Study.1 One limitation of that study was uncertainty as to whether the catch-up cohort had actually received HPV (human papillomavirus) vaccination. That information has now been obtained. 87 (59%) of the 147 patients in the catch-up cohort had received at least one dose of HPV bivalent vaccine. 69 of these (representing 79% of those vaccinated) had received three doses (as recommended at the time). Both the vaccinated and unvaccinated subsets of the catch-up cohort show a significant reduction in the prevalence of HPV 16 and/or 18 (with/without other high-risk types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) and of high grade cervical disease compared to an earlier unvaccinated cohort. These results confirm the efficacy of HPV catch-up vaccination and the existence of herd immunity following the introduction of national HPV vaccination campaigns. However, 34 patients (23%) in the catch-up cohort had high grade disease (cervical intraepithelial neoplasia [CIN] 2 or worse), 16 of whom had been vaccinated (12 with three doses, one with two doses and three with one dose of HPV bivalent vaccine) and four of those vaccinated had HPV 16 and/or 18 (with/without other high-risk types), the rest had other HPV high risk types. This emphasises the importance of maintaining cervical screening alongside HPV vaccination.