All Articles

Gavin Yuen*, Saundarai Bhanot^#, Jeremy Steen, Minahil Syed, Austin Mardon^#

Sharpen the Quill, Ontario, Canada

Vaccination is a powerful inducer of immunity against SARS-CoV-2 and its recent variants. However, it is important to expand the defensive repertoire against this virus as vaccination is not always efficacious or accessible to everyone. Protein therapeutics in the form of monoclonal antibodies have been used to neutralize the Spike protein, but their efficacy has been limited with rapidly evolving mutations. Cocktail antibodies have been used to combat antigenic escape through diversifying antigen recognition and the overall neutralization capacity. However, the production of cocktail antibodies can be costly and requires a high dosage to achieve the desired therapeutic effect. Alternatively, bispecific antibodies have been used, which contain two recognition specificities within the same molecule. This effectively reduces the cost of production and dosage required to achieve a target therapeutic effect. Bispecific antibodies were reported to bind SARS-CoV-2 antigen with nanomolar affinities. The neutralization potentials (IC50 values) within the same studies were generally more efficacious than their cocktail antibody counterparts. Some studies showed that bispecific antibodies could also confer additional neutralization effector functions, such as recruiting the complement system. Although the recognition of variants was diverse, to our knowledge, there is no data to suggest that bispecific antibodies have a broader recognition of variant strains than cocktail antibodies. Future studies should aim to explore the clinical benefits of bispecific antibodies for SARS-CoV-2 and the emerging variant strains to better understand its benefits in treatment.

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

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) genes have been associated with susceptibility and protection against a number of cancers. Here we used an immunogenetic epidemiological approach to evaluate the overall influence of 127 HLA Class I and II alleles on 30 types of cancer. We found a preponderance of protective alleles (negatively correlated with cancer prevalences), especially for HLA Class I. Of the 30 cancers investigated, 13 were associated with mostly protective HLA effects whereas only 2 were associated with mostly susceptibility HLA alleles. Taken together, these findings highlight the broad influence of HLA on cancer and the complexity of HLA-cancer associations.­­

Raquel García-Belmonte, Daniel Pérez-Núñez, Yolanda Revilla^*

Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Microbes in Health and Welfare Department, c/ Nicolás Cabrera, 1, 28049 Madrid, Spain

Yuxi Yan^1#, Quan Zhao^1#, Ya Huang¹, Janine Y. Yang², Jie Zou¹, Chunxia Ao¹, Xiaojuan Chai¹, Renhong Tang¹ and WenQing Yang^1*

¹State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, Jiangsu, China.

²Massachusetts Eye and Ear, Harvard Medical School, USA

Background and objective

Experimental autoimmune encephalomyelitis (EAE) is the most commonly used model for studying autoimmune-mediated myelin degradation in multiple sclerosis (MS). Here, we evaluated the pharmacologic responses of several anti-inflammatory drugs with varying mechanisms of actions (MOAs) using EAE models induced by different MOG immunogens to reveal differential pharmacologic characteristics of the disease models and provide a general guidance in animal model selection for MS research.

Methods

The pharmacologic responses of anti-inflammatory drugs with different mechanisms of actions (MOAs) were evaluated using EAE models induced by either myelin oligodendrocyte glycoprotein p35-55 (MOG_35-55)  or p1-128 (MOG_1-128). EAE animal models were developed in mice with C57BL/6 background. The animals were treated with different anti-MS medications, including 3 B cell-mediated agents and 2 T cell-mediated agents, respectively. Clinical symptoms were monitored and scored, and pharmacodynamic markers including cytokine secretion, inflammatory cell infiltration, and demyelination in spinal cord were analyzed.

Results

In MOG_35-55 peptide-induced EAE model, T cell modulating agents Secukinumab and Fingolimod significantly alleviated clinical symptoms, while B cell-depleting agents, BTK inhibitors PRN2246 and Telitacicept, displayed minimal therapeutic effects or even exacerbated disease progression. In contrast, both T cell-modulating agents and B cell-depleting agents ameliorated disease severity in MOG_1-128-induced EAE model. T cell and B cell infiltration in spinal cord increased with disease progression in MOG_1-128-induced EAE model.

Conclusions

Our results demonstrated that induction of EAE by different myelin antigens resulted in differential pharmacologic responses to drugs with specific MOAs. The MOG_35-55 peptide-induced EAE model only responded to T cell-modulating drugs, whereas the MOG_1-128 protein-induced EAE model exhibited therapeutic sensitivity to both T cell- and B cell-modulating agents. These data suggest the MOG_35-55 peptide-induced EAE model is suitable for assessing T cell-modulating agents while MOG_1-128 protein-induced model can be employed to evaluate both T cell- and B cell-modulating agents.

Dave M. Mathew BS, Kathryn S. Varghese BS, Serena M. Mathew, Roshan Pandey, Sarah Ahmed, Stephanie A. Salazar BS, Dillon O. Rogando BS, Peter J. Fusco BS, Kenneth H. Levy BS, Adham Ahmed BS*

City University of New York (CUNY) School of Medicine, New York, New York

Jin Hyang Kim^1,2#, Grace Park³, Bhavna Paratala^1,4, Rene Rijnbrand^1,5, Michael J. Sofia¹ and Hie-Won Hann^3*

¹Arbutus Biopharma Corporation, 701 Veterans Circle, Warminster, Pennsylvania, 18974, US

²Current address: Bristol Myers Squibb, 3401 Princeton Pike, Lawrenceville, NJ 08648, US

³Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, US

⁴Current address: Adaptimmune LLC, 351 Rouse Boulevard, Philadelphia, PA 19112, US

⁵Current address: Dicerna Pharmaceuticals, 33 Hayden Ave, Lexington, MA 02421

Hepatitis B virus (HBV) is a main cause of hepatocellular carcinoma (HCC) development. Although controversial, it is increasingly recognized that the immune responses directed against infected hepatocytes drive hepatic inflammation and tissue injury. Here we extended our previous findings to report that serum surface antigen (HBsAg) levels are a biomarker not only for HBV-specific immunity, but also for ongoing non-specific immune activation. We found that the HBV-specific T cell responses in patients with HBsAg < 500 IU/mL, while significantly higher than those in patients with HBsAg > 50,000 IU/mL, had already reached levels comparable to patients with seroclearance. In addition, lower HBsAg levels were associated with reduced non-specific immune activation, while no further reduction was observed with HBsAg < 500 IU/mL. We propose HBsAg is a therapeutic target for reducing inflammation.

Paul F. Cotter

Cotter Laboratory, Arlington, MA, 02476, USA

The aim is to describe the array of plasmacytes (PC), cells known as the source of antibody, occurring in the bone marrow (BM) of lame ducklings. The method is by a light microscopic examination of touch preparation slides made from femur samples and stained with Wright-Giemsa. Samples were obtained on site at commercial farms where slide preparations were made; reducing the possibility that observations are technical artifacts.

The results: indicate that PC occur in a multitude of sizes, shapes, nuclear/cytoplasmic (N/C) ratios, ploidy, and nuclear and cytoplasmic conditions. Normal PC are illustrated first, followed by atypical forms. Some PC are presented in the context of neighboring BM cells of the granulocyte, erythrocyte, and reticulum cell (histiocyte) series.

More than 100 Mott-type PC were measured in a single sample from a 13-day lame duck; and several distinct forms were identified. Size, as measured by their longest axis, varied from 6.1 to 28 μm and it appears to be normally distributed. Moreover, N/C ratios were distributed across a three-fold range (0.3 – 0.9) indicating Mott phenotypes can occur at multiple developmental stages. Motts differed in Russell Body (RB) size, and nuclear condition. A novel Mott type, “orb” form, with partially lysed nuclei is also described.

PC were often found in association with giant granulated histiocytes (ggh) and non-granulated giant histiocytes (gh). Other atypical forms are “hand-mirror” PC, trinucleate and binucleate PC resembling cells seen in multiple myeloma (MM) and lymphomas.

 Collectively these PC variants constitute “reactive plasmatosis” (RP) likely arising as a consequence of the presence of various bacteria including Streptococcus and E. coli.            

The conclusions: It is demonstrated that RP as occurs in lame ducklings suffering from bacterial infections, provides a unique theater for the study of PC variability. Atypical PC, some resembling neoplastic types, were common in RP BM. The significance of the study relates to the importance of PC in disease and immunity; therefore, these observations should interest those who specialize in these areas. They expand the knowledge of avian plasmacyte morphology.

Nicholas Noverati¹, Daniel Garrido^1,2, Dina Halegoua-DeMarzio^1,2, Hie-Won Hann^1,2,3*

¹Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107 USA

²Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107

³Liver Disease Prevention Center, Thomas Jefferson University Hospital, Philadelphia, PA 19107 USA

Introduction: Chronic hepatitis B virus (HBV) infection is prevalent worldwide and up to 40% is known to progress to serious complications including cirrhosis and hepatocellular carcinoma (HCC). The outcome of the remaining infected individuals is not well documented. Our case series describes a longer cohort of chronic HBV infections that have remained asymptomatic with no progression of liver disease.

Case Series: Thirty-three patients (ages 31-84) with chronic HBV infection were identified. All patients had no significant elevations in transaminase levels and were followed over 32 years, collectively. 18/33 had a fluctuating greater magnitude of HBV viral load with no elevations in tumor marker or significant radiographic changes to their liver.

Discussion/Conclusion: Chronic HBV infection can lead to serious complications over time, the mechanism of which are not well understood. The variation in patients that do and do not develop these complications stresses the importance of the individual response to the virus and may highlight host immune response differences.

Spyros A. Charonis^1,2, Apostolos P. Georgopoulos^1,2*

¹The HLA SARS-CoV-2 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

Paul F. Cotter

Cotter Laboratory, Arlington, MA 02476, USA

The aim is to demonstrate a variety of apoptotic heterophils (equivalents of mammalian neutrophils) occurring in hemograms of 50 apparently healthy pullets housed in cages. These atypical cells are found in blood with normal total white cell levels (TWBC, ~20K) and in those ranging up to 100(K) a leukocytosis/leukemoid reaction level. Conversely heterophil/lymphocyte (H/L) ratios in all hens ranged between 0.14 – 0.50 (homeostasis). The Arneth index (a heterophil age measure) of 1.8 computed using only intact heterophils indicated a “left-shift”, suggesting inflammation even in the context of a normal hemogram.

The results: atypical heterophils with condensed (pyknotic) and fragmented nuclei (karyorrhexis), ruffled cytoplasmic membranes (zeiosis), apoptotic body formation, and other characteristics of apoptosis circulated in the blood of the study hens. Highly unusual cells as a monocyte containing a phagocytosed apoptotic body composed of heterophil granules, and a Mott cell (atypical plasmacyte) were also found.

More importantly, heterophils displaying thin, swollen and externalized nuclei suggestive of an unusual form of karyolysis were present. These cells were often seen in the company of free or RBC associated bacteria and fungi. There were also two examples of bacteria phagocytosed by apoptotic cells.

Other types of apoptotic cells were in 16/50 (32%) of hens from the study sample. These included small and medium size lymphocytes, monocytes, and metamyelocytes. Frank evidence of bacteremia (5/50, 10%) fungemia (4/50, 8%) and both (1/50, 2%) were detected. This suggests a relation between hematological atypia and the presence of circulating microorganisms possibly mediated through the release of toxins. Atypia of the circulation are sentinels, an alert to investigators or clinicians who are interested in the relation between the composition of blood and stress measurement or disease.

Conclusions: these observations apply to apparent morphologic plasticity of the heterophil, its role in the innate immune system, and its use in determining stress. In the cases described here the initial computation of the H/L ratios suggested the absence of stress. Moreover, this occurred in the context of either a normal or a high TWBC. However, heterophil age indicated a left-shift; a population predominated by young cells. This situation occurs when there is a demand to replace cells that have left the circulation either due to inflamed tissues or to death while circulating. Therefore, circulating apoptotic cells suggest stress even when the H/L is low and the TWBC is normal.

Kerstin S. Baun¹, Nathan T. Kearns², Jennifer K. Peterson¹, John M. Miguelez¹

¹Clinical Services, Advanced Arm Dynamics, Redondo Beach, CA, USA

²Department of Psychology, University of North Texas, Denton, TX, USA

Abstract

Purpose: 

To develop and psychometrically evaluate the Comprehensive Arm Prosthesis and Rehabilitation Outcomes Questionnaire (CAPROQ), a 28-item, self-report measure of three key facets associated with successful rehabilitation (perceived function, satisfaction, and pain) designed specifically for the adult upper limb loss (ULL) population.

Materials and Methods:

Using a national sample of adult ULL patients (N=240), factor structure, internal consistency, convergent/concurrent validity, and known group validity of the total CAPROQ score and three subscale scores were evaluated.

Results:

Confirmatory factor analysis indicated adequate-to-strong factor loading on each subscale: satisfaction (.623-.913), perceived function (.572-.860) and pain (.422-.834).  Internal consistencies for the total measure and measure subscales were good-to-excellent (.89-.95) and convergent validity indicated moderate-to-strong statistically significant associations between the CAPROQ subscales and relevant measures. Concurrent validity showed moderate associations between CAPROQ total score, prosthetic wear time, and psychosocial adjustment scores. Known group validity indicated significant differences on CAPROQ total score between initial and definitive fitting stages (p=.012).

Conclusion:

Psychometric evaluation indicated that the CAPROQ and CAPROQ subscales were structurally sound, internally consistent, and demonstrated convergent validity with currently used assessments of perceived functioning, satisfaction, and pain.  CAPROQ is needed for guiding individual patient care, improving care models and future prosthesis selection and development.

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) 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.

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

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.

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.

Lisa M. James^1,2,3, Spyros A. Charonis^1,2, 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), 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.

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.

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.

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.

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.

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.

Priyanka Ray

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

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.

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.

Samuel Okiror¹*, John Ogange², Hemant Shukla³, Christine Lamoureau⁴, Mwaka Monze⁵, Amina Ismail², Anthony Kazoka⁶, Ben Nkowane³, Raoul Kamadjeu⁷, Obianuju Igweonu⁸, Joseph Okeibunor⁹, Chidiadi Nwogu¹

¹WHO Horn of Africa Coordination Office (HOA), Nairobi, Kenya

²World Health Organization, Kenya Country Office

³WHO Headquarters, Geneva

⁴Independent Consultant

⁵Polio Laboratory, Zambia

⁶World Health Organization, Tanzania Country Office

⁷UNICEF, New York

⁸University of Nigeria, Nsukka

⁹WHO Regional Office for Africa (WHO AFRO) Brazzaville, Congo

Background: The risk for importation and reintroduction wild poliovirus in areas that have been cleared of the wild poliovirus in the Horn of Africa will remain if the surveillance systems are weak and porous. Methods: Consequently, the Horn of Africa Polio Coordinating Office in Nairobi, together with partners conducted surveillance reviews for some of the countries in the Horn of Africa, especially Ethiopia, Kenya and Somalia to identify gaps in the polio surveillance and provided recommendations for improved surveillance. Structured questionnaires collected information about acute flaccid paralysis (AFP) surveillance resources, training, data monitoring, and supervision at provincial, district, and health facility levels. Other information collected included resource availability, management and monitoring of AFP surveillance.Results: The result revealed that although AFP surveillance systems were well established in these countries, a number of gaps and constraints existed. Widespread deficiencies and inefficient resource flow systems were observed and reported at all levels. There were also deficiencies related to provider knowledge, funding, training, and supervision, and were particularly evident at the health facility level. These weaknesses were corroborated with the sustained transmission of polioviruses in the region, where the surveillance systems were not sensitive enough to pick the viruses. Conclusion: The review teams made useful recommendations that led to strengthening of the surveillance systems in these countries, including the formation and use of village polio volunteers in the south and central zones of Somalia, where security was heavily compromised and surveillance officers lacked regular access to the communities.

Bernard Ntsama¹, Ado Bwaka², Reggis Katsande³, Regis Maurin Obiang⁴, Daniel Rasheed Oyaole⁵, Pascal Mkanda⁵, Joseph Okeibunor⁵

¹Data Manager, IST West Africa

²IVD/PEP Focal Point, IST West Africa

³Data Manager, AFRO

⁴Data Manager, IST Central Africa

⁵Data Manager, WHO Nigeria

The polio Eradication Initiative (PEI) is one of the most important public health interventions in Africa.  Quality data is necessary to monitor activities and key performance indicators and access year by year progress made. This process has been possible with a solid polio health information system that has been consolidated over the years.

This study describes the whole process to have data for decision making.  The main components are the data flow, the role of the different levels, data capture and tools, standards and codes, the data cleaning process, the integration of data from various sources, the introduction of innovative technologies, feedback and information products and capacity building. The results show the improvement in the timeliness of reporting data to the next level, the availability of quality data for analysis to monitor key surveillance performance indicators, the output of the data cleaning exercise pointing out data quality gaps, the integration of data from various sources to produce meaningful outputs and feedback for information dissemination.

From the review of the process, it is observed an improvement in the quality of polio data resulting from a well-defined information system with standardized tools and Standard Operating Procedures (SOPs) and the introduction of innovative technologies. However, there is room for improvement; for example, multiple data entries from the field to the surveillance unit and the laboratory. Innovative technologies are implemented for the time being in areas hard to reach due to the high cost of the investment. 

A strong information system has been put in place from the community level to the global level with a link between surveillance, laboratory and immunization coverage data. To maintain standards in Polio Information system, there is need for continuous training of the staff on areas of surveillance, information systems, data analysis and information sharing. The use of innovative technologies on web-based system and mobile devices with validation rules and information check will avoid multiple entries.