All Articles

Wolters ECh¹, de Hoo K², Kramer BW³, de Munter JPJM^2,4

¹Department of Neurology, UniversitatsSpital Zurich, Zurich, Switzerland

²Neuroplast BV, Urmond, The Netherlands

³Department of Paediatrics, Maastricht University Medical Centre, Maastricht, The Netherlands

⁴School for Mental Health and NeuroScience, Maastricht University, Maastricht, The Netherlands 

A cytokine release syndrome (CRS), associated with elevated circulating levels of several cytokines including interleukin (IL)-6 and interferon (IFN)-γ, might be seen in some infectious insults, for instance in severe acute respiratory syndrome (SARS) induced by Coronavirus (Cov)-2, as well as following administration of natural and bispecific antibodies and, more recently, following adoptive T-cell therapies for cancer. Normally, inflammatory conditions activate the innate and adaptive immune systems, which results in the release of cytokines, responsible for the phagocytosis of apoptotic vesicles and resolution of inflammation. Pro-inflammatory cytokines such as IL-1β, tumor necrosis factor alpha (TNFα) and, especially in chronic inflammatory diseases, autoimmune diseases, cancer and cytokine storms, IL-6 play crucial roles in inflammation. In some instances, however, this release gets out of hand, and features of overzealous immune responses (macrophage activation syndromes) might occur, leading to cytokine release syndromes (CRS) with inflammatory signs such as fever, fatigue, nausea, and sometimes secondary organ dysfunction or multi-organ failure. Apart from specific vaccines and maybe the anti-viral remdesivir and/or dexamethasone for treatment of CRS, there are no convincing disease-modifying interventions. So far, though, non-antiviral and immune-targeted interventions, also affecting non-target cells, were found associated with many side effects. A more targeted or focused approach is thus needed. Pending the site of the CRS-inducing insult, CRSs may occur systemic or compartmental. Recently, preclinical research yielded a beneficial anti-inflammatory effect of fresh naive bone marrow-derived stem cells (bm-SCs) in the treatment of various compartmental CRSs in the immune-privileged central nervous system (CNS). Therefore, it is argued that bm-SCs might also play a disease-modifying role in the systemic CRS. Bm-SCs have the advantage of targeting only the cells of interest as they are very selective in their actions. In addition, they actively move to the sight of inflammation.

Priyanka Ray¹, Noor Haideri², Inamul Haque², Omar Mohammed², Saborni Chakraborty², Snigdha Banerjee^2,3#, Mohiuddin Quadir^1#, Amanda E. Brinker ^4,5, and Sushanta K. Banerjee^2,3*

¹Department of Coatings and Polymeric Materials, North Dakota State University, Fargo, ND

²Cancer Research Unit, VA Medical Center, Kansas City, MO

³Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS

⁴Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS

⁵Institute for Advancing Medical Innovation, University of Kansas Cancer Center, Kansas City, KS

Since the early days marking the first use of nanomedicine in the early 80s, there has been a meaningful change in the scientific field involving the Fabrication, characterization, and application of nanomaterials to treat many diseases, including cancers and genetic disorders. As unique and attractive properties of this novel class of materials unraveled, significant advances and discoveries were made over time. Addressing several challenges posed by conventional therapy, which were the only available treatment option for ailing patients, nanomedicine provided enhanced benefits, including reduced dosing, improved pharmacokinetics, and superior targeting efficiency. Several such formulations have successfully made their way to clinics and have shown promise in prolonging terminally ill patient populations' survival rates. However, the complex immune system and its various components, including various proteins and surface receptors, have made nanomaterials' journey from benchtop to the bedside a treacherous one. The innate and adaptive immune system interactions with nanomaterials are still under investigation and full of mysteries. This review highlights the various aspects of therapeutic nanocarriers and their current understanding of their immune systems' interactions.

Lisa M. James^1,2,3, Rachel A. Johnson¹, Scott M. Lewis^1,4, Adam F. Carpenter^1,4, Brian E. Engdahl^1,2,5, Hollis E. Krug^6,7, Apostolos P. Georgopoulos^1,2,3,4*

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

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

⁶Department of Rheumatology, Department of Veterans Affairs Health Care System, Minneapolis, MN, 55417, USA

⁷Department of Rheumatology, University of Minnesota Medical School, Minneapolis, MN 55455, USA

Mounting evidence suggests that autoimmune mechanisms may underlie the chronic symptoms characteristic of Gulf War Illness (GWI). The presence of antiphospholipid antibodies including Lupus Anticoagulant (LA) are often associated with autoimmune disorders. Here we evaluated and compared blood samples from veterans with GWI and veterans with other autoimmune conditions including relapsing remitting multiple sclerosis, rheumatoid arthritis, Sjögren’s syndrome, and lupus for the presence of LA using Silica Clotting Time and dilute Russell’s Viper Venom Time assays. Positive LA was identified in one-quarter of veterans with GWI; this proportion was not statistically different from the proportion of positive LA identified in patients diagnosed with the other autoimmune conditions. The present findings add to the literature implicating autoimmune mechanisms in GWI and point to the presence of prothrombotic antiphospholipid antibodies as a common contributing factor in GWI and other autoimmune disorders. Furthermore, activation of the coagulation system suggests new potential avenues for treatment for LA-positive Gulf War veterans.

Christian B. Auclair^* & Annette Ives^#

AC BioScience SA, Biopôle, Route de la Corniche 4 – Lysine, 1066 Epalinges, Switzerland

Brandon C. Smith^1,2 & Jessica L. Williams^1*

¹Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

²Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, OH, USA

Despite an increase in approved therapies for treating the inflammatory and neurodegenerative disease multiple sclerosis (MS), many of which have efficacy in the early, acute phases, there are no reliable treatments for the chronic, progressive stages of the disease. A deeper understanding of the biological underpinnings that govern differences between acute and chronic stages of MS and an animal model of MS, experimental autoimmune encephalomyelitis, will inform therapeutic development and personalized treatment strategies. It is well-known that the effects of inflammation are complex and the implications vary between stages. Complimentary to our recent publication, we will discuss here the pleiotropic effects of the cytokine interferonγ across disease states, along with the implications of downstream mechanisms of action.

Shinya Tanaka^1*, Wataru Ise², Yoshihiro Baba¹, Tomohiro Kurosaki^2,3#

¹Division of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, 812-0054, Japan

²Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka, Suita, 565-0871,Japan

³Laboratory of Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan

Gene expression must be strictly controlled during cell differentiation and function in mammalian systems. DNA methylation plays an important role in this process, and its pattern is shaped by balancing the activity of methyltransferases and demethylases. Ten-eleven translocation (TET) was identified as a demethylase that catalyzes the oxidation reaction of the methyl group of 5-methylcytosine (5mC), converting it to 5-hydroxymethylcytosine (5hmC). Recently, indispensable roles of TET proteins in the regulation of immune cells have been identified. Here, we review recent studies on the biological consequences of dysregulation of TET proteins in the immune system, with a particular focus on B cell biology. Finally, we discuss future perspectives in this research field.

Giovanna L. Gallo^1*, Julieta S. Roldán², Laura R. Delgui^3,4

¹Centro de Virología Animal (CEVAN)-CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas).

²Instituto de Investigaciones Biotecnológicas "Dr. Rodolfo A. Ugalde" (IIBIO), Universidad Nacional de San Martín (UNSAM) - CONICET, San Martín, Buenos Aires, Argentina.

³Instituto de Histología y Embriología de Mendoza (IHEM-CONICET). Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina.

⁴Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Mendoza, Argentina.

Mammarenavirus genus groups viruses causing human haemorrhagic diseases, including the New World (NW) Junín virus (JUNV), and the Old World (OW) viruses Lassa (LASV), among others. The high mortality and morbidity rates associated to pathogenic mammarenaviruses, the absence of vaccines and the constant threat of new emerging species, make these viruses a public health concern in endemic areas. Autophagy is a widely-known intracellular metabolic pathway involved in maintaining the cellular homeostasis in response to several stress conditions.

R. Christina Smith, MD¹, Meera N. Patel², Richard Sigmon, MD³, Niraj C. Patel, MD, MS¹

¹Division of Pediatrics, Division of Pediatric Infectious Disease and Immunology, Atrium Health, Charlotte, NC, USA

²North Carolina School of Science and Math

³Department of Internal Medicine, Division of Gastroenterology, Atrium Health, Charlotte, NC, USA

The licensed rotavirus vaccines are live attenuated and are a component of the routine U.S. childhood immunization schedule. Live vaccines administered to infants of mothers who received biologic response modifiers (BRM) during pregnancy can potentially cause serious vaccine-associated disease. The Advisory Committee on Immunization Practices (ACIP) recommends infants born to women who received BRM during pregnancy avoid live viral vaccines during the first year of life. There is a paucity of information regarding adverse events following inadvertent administration of live viral vaccines in these infants. We report three infants, born to mothers receiving infliximab during pregnancy, who tolerated multiple doses of rotavirus vaccine. Live viral vaccines may be safe in infants who were exposed to BRM in utero. Further studies are needed to support this observation, as this could affect current ACIP recommendations.

Anurag Singh¹, Lakshya Gupta², Vandana Gupta¹*

¹Department of Microbiology, Ram Lal Anand College, University of Delhi, Benito Juarez Road, New Delhi 110021, India

²Department of Computer Science and Engineering, Indian Institute of Technology, Varanasi, Uttar Pradesh 221005, India

The coronavirus disease (COVID-19) emerged in China in December 2019 and has since spread to over 188 countries affecting millions of individuals. Several reports in favour or against the heterologous protection conferred by the BCG vaccine against COVID-19 came up in the initial days of the pandemic and continue to do so. In this study, we compared the three worst-affected nations: The USA, India, and Brazil, their current pandemic scenario, and their respective national BCG immunization policies. USA recommends BCG vaccine only to a specific group of people and never had a national immunization scheme in place. Meanwhile, India introduced a nationwide scheme as early as 1948 and continues to endorse BCG immunization at birth. Brazil used the oral route to administer the BCG vaccine till 1976, and then shifted to intradermal injection. The correlation coefficient for the total number of cases, cases per million, the total number of deaths, deaths per million and case fatality rate ranges between 0.81-0.98. This indicates a very strong positive correlation in the various epidemiological parameters between countries with no national immunization scheme (USA) and countries with stringent national policies on BCG vaccination. The strongest correlation exists between the USA and Brazil followed by Brazil and India which is very closely followed by the USA and India. We found no consistent evidence to infer in favour of the hypothesis that BCG provides any non-specific protection against COVID-19.

Abbreviations

BCG: Bacillus Calmette-Guérin

COVID-19: Coronavirus Disease 2019

DPT: Diphtheria, Pertussis, and Tetanus

HPV: Human Papillomavirus

HSV: Herpes Simplex Virus

ICTV: International Committee on Taxonomy of Viruses

OPV: Oral Poliovirus Vaccine

RSV: Respiratory Syncytial Virus

SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2

TB: Tuberculosis

WHO: World Health Organization

Sara B. Intner¹, Michelle Altrich², Niraj C. Patel¹

¹Department of Pediatrics, Levine Children’s Hospital, Atrium Health, Charlotte, NC, USA

²Viracor Eurofins, Lee’s Summit, MO, USA

Measurement of pneumococcal antibody concentration is a frequently used parameter for functional antibody response to vaccination. Antibody concentration in response to vaccination and strength of antigen-antibody (avidity) interaction are both important measurements of functional antibody response. Both antibody concentration and avidity contribute to immunity against invasive pneumococcal disease. Higher avidity is correlated with increasing bactericidal activity and opsonophagocytosis. On the other hand, patients with lower pneumococcal avidity may be more likely to develop clinically significant pneumococcal sinopulmonary infections. Nine patients with recurrent bacterial respiratory infections were identified by retrospective chart review as having adequate pneumococcal antibody concentrations, but with low avidity for multiple serotypes following immunization with pneumococcal vaccine polyvalent (PPSV23). We assessed response with IgG replacement therapy in these patients. The mean number of serotypes with a normal antibody response (>1.3 𝛍g/ml) among 9 children following immunization with pneumococcal vaccine polyvalent was 19.1 (range 12-22) of 23 serotypes while the mean number of serotypes with a normal avidity response (≥1.0) was 4.7 (range 2-7) of 23 serotypes. Flow cytometry was performed for 8 of the 9 patients prior to starting SCIG replacement therapy. 100% of the cohort experienced a significant decrease in yearly infection rate after starting immunoglobulin replacement. This is the first study to assess the clinical response to immune globulin replacement in patients with normal pneumococcal antibody response but poor pneumococcal avidity, and suggests that patients with poor pneumococcal avidity but apparent normal response by pneumococcal antibody following PPSV23 may benefit from IgG replacement therapy.

Lisa M. James^1,2,3,4, Effie-Photini C. Tsilibary^1,2, Spyros Charonis^1,2, Apostolos P. Georgopoulos^1,2,3,4*

¹ Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, USA

² Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA

³ Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA

⁴ Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, USA

Spyros S. Charonis ^1,2, Effie-Photini Tsilibary ^1,2, Apostolos P. Georgopoulos ^1,2*

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

SARS-CoV-2 causes COVID-19, urgently requiring the development of effective vaccine(s). Much of current efforts focus on the SARS-CoV-2 spike-glycoprotein by identifying highly antigenic epitopes as good vaccine candidates. However, high antigenicity is not sufficient, since the activation of relevant T cells depends on the presence of the complex of the antigen with a suitably matching Human Leukocyte Antigen (HLA) Class II molecule, not the antigen alone: in the absence of such a match, even a highly antigenic epitope in vitro will not elicit antibody formation in vivo. Here we assessed systematically in silico the binding affinity of epitopes of the spike-glycoprotein to 66 common HLA-Class-II alleles (frequency ≥ 0.01). We used a sliding epitope window of 22-amino-acid-width to scan the entire protein and determined the binding affinity of each subsequence to each HLA allele. DPB1 had highest binding affinities, followed by DRB1 and DQB1. Higher binding affinities were concentrated in the initial part of the glycoprotein (S1-S460), with a peak at S223-S238. This region would be well suited for effective vaccine development by ensuring high probability for successful matching of the vaccine antigen from that region to a HLA Class II molecule for CD4⁺ T cell activation by the antigen-HLA molecule complex.

Ioanna Zerva, Vasileia Pateraki, Irene Athanassakis*

Department of Biology, University of Crete, Vassilika Vouton, Heraklion 70013, Crete, Greece

Effective and side-effect-free vaccines are still difficult tasks to achieve for a great majority of antigenic stimuli. Pathogen manipulation to abort infectivity and antigen delivery to ensure immune responsiveness are the major components vaccine technology tries to resolve. However, the development of an immune response is still a complicated matter, lies on hundreds of parameters and any effort towards activation can easily lead to adverse effects, making immunotherapy very difficult to control. The present review attempts to highlight the major parameters affecting immune responsiveness and show that vaccine technology, except from pathogen manipulation and the development of antigen delivery systems, requires attention to additional check-points. Analyzing the recently described personalized implantable vaccine technology, it becomes obvious that the nature of each antigenic stimulus dictates different responsiveness to the organism, which discourages the use of universal adjuvant and antigen-delivery systems. On the contrary, the ex vivo tuning of the immune response proposed by the implantable vaccine technology, allows controllable amendment of the response. The development of personalized technologies is expected to provide valuable tools for the management of human pathology.

Priya Jeyaraj

Commanding Officer, Military Dental Centre (Gough Lines), Secunderabad, Telangana, Pin- 500015, India

Introduction: Establishing an accurate diagnosis and probable prognosis of ambiguous, extensive and destructive maxillary pathologies, is imperative for an appropriate, timely and effective treatment modality to be instituted. This is particularly true in the paediatric population, in order to ensure complete elimination of the lesion, with the least possible morbidity, debility, or interference with normal jaw growth.

Objectives: To assess the diagnostic and prognostic value of Immunohistochemistry (IHC) as an adjunct to Histopathological examination (HPE), in cases of destructive paediatric maxillary pathologies. To use the information thus obtained, to select the most ideal and efficacious management protocol for each case.

Material & Methods: An extensive study was carried out on 25 cases of destructive (as evidenced clinically and radiographically) maxillary lesions, in children of ages between 5 and 16 years. Positivity for an IHC tumor marker, namely Calretinin, was employed to distinguish maxillary cysts from tumors. In addition, Labelling indices of two IHC cell proliferation markers, namely Ki-67 and PCNA, indicated the proliferative activity of constituent cells of the pathologies, which aided in predicting their aggressive nature and recurrence potential. On the basis of the above information, the choice between a conservative versus radical treatment approach was made for each individual case.

Results & Conclusion: IHC proved to be of immense value as a diagnostic marker and a prognostic indicator in the paediatric maxillary pathologies. In addition to aiding the pathologist in making an accurate confirmatory diagnosis, it also served as an invaluable tool to the surgeon, in guiding the treatment plan by indicating the likely prognosis and chances of recurrence of these lesions.

Oluwatoyin Adenike Adeyemo-Salami

Department of Biochemistry, College of Medicine, University of Ibadan, Oyo State, Nigeria

Anything that affects the absorption of nutrients and intestinal function will invariably affect the physical well-being or the health status of an individual. Cystic fibrosis is a disease condition that is autosomal recessive and affects organs that have epithelia including the gastrointestinal tract of which the intestine is part, and is the one that is primarily affected. The major aberration responsible for it is mutations in the cystic fibrosis transmembrane conductance regulator gene. Phenotypical evidence of cystic fibrosis in the intestine includes obstruction, microbial dysbiosis, inflammation, acidity in the intestinal tract, malnutrition, immune dysfunction, intestinal dysmotility, appendiceal aberrations and intussusception. All these manifestations result in maldigestion and malabsorption of lipid, protein and carbohydrate in the intestine. The effect of cystic fibrosis on the digestion of certain micronutrients was also reported.

In this review, the pathophysiology, manifestations of cystic fibrosis in the gastrointestinal tract with emphasis on the small intestine, and the effects on digestion of macronutrients and micronutrients would be discussed.

Chandreyee Datta, Ashish Bhattacharjee*

Department of Biotechnology, National Institute of Technology, Durgapur, 713209, West Bengal, India.

Corona virus disease 2019 (COVID-19), is a viral disease caused by novel corona virus known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). The disease was declared as a pandemic by the World Health Organisation (WHO) on March 11, 2020. Initial studies have shown the molecular resemblances in the receptor binding domains of SARS-CoV and SARS-CoV-2 which bind angiotensin converting enzyme 2 (ACE 2) receptors and helps the virus to enter into the host cells to cause infection. Illness caused by COVID19 ranges from mild common cold to life threatening acute respiratory distress syndrome (ARDS), multi-organ dysfunction and shock. The key step in converting mild disease to severe is immune dysfunction and cytokine dysregulation resulting in “cytokine storm syndrome”. Clinical investigations in patients with COVID-19 have shown that a strong upregulation of cytokine and interferon production is common feature in SARS-CoV2-induced pneumonia, with an associated cytokine storm syndrome. Consequently, spotting of existing approved therapies with proper safety profiles to treat hyperinflammation is very essential in order to reduce COVID-19 associated mortality. Till date, no specific therapeutic drugs or vaccines are available to treat COVID-19. In this review, we intended to describe how cytokine storm is associated with the severity of COVID-19 disease and also tried to find out the best possible way to manage the hyperinflammatory response due to cytokine storm during COVID-19 infection using several interleukin receptor antagonists, inhibitors, intravenous immunoglobulins, cytokine adsorption device and repurposing of pre-existing antiviral and some antimalarial drugs etc.

Nick F. Hallam¹*, Janet A. Parker²

¹Colposcopy Clinic, Women's Outpatients, Cumberland Infirmary, Carlisle, England, United Kingdom

²Manchester Cytology Centre, Division of Laboratory Medicine, Manchester University, NHS Foundation Trust, Manchester, England, United Kingdom

Malgorzata Kloc*^1,2,3, Rafik M. Ghobrial^1,2, Jacek Z Kubiak*^4,5

¹The Houston Methodist Research Institute, Houston, Texas 77030, USA

²The Houston Methodist Hospital, Department of Surgery, Houston, Texas, USA

³The University of Texas, M.D. Anderson Cancer Center, Department of Genetics, Houston Texas, USA

⁴Laboratory of Regenerative Medicine and Cell Biology, Military Institute of Hygiene and Epidemiology (WIHE), Warsaw, Poland

⁵UnivRennes, UMR 6290, CNRS, Institute of Genetics and Development of Rennes, Cell Cycle Group, Faculty of Medicine, Rennes, France

The interferons (IFNs) are the main antiviral immune factors. Currently, various IFNs therapies are used for the treatment of human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV), cancer, and autoimmune diseases. Recently, it has been suggested that IFN-α therapy should be used to lessen the respiratory symptoms in the SARS-CoV-2 virus- infected (COVID-19) patients. The SARS-CoV-2 enters the cells by binding to the Angiotensin-converting enzyme 2 (ACE2), which by recognizing the spike S1 protein of the virus, acts as a virus receptor. Because the expression of ACE2 is induced by IFN-α, the SARS-CoV-2 virus may exploit the anti-viral response by subverting the IFN functions to further its own propagation and infectability. We discuss here how the SARS-CoV-2 may also subvert the immune response of the lung macrophages, which also express ACE2, to exacerbate the severity of the COVID-19 respiratory symptoms.

Dana Khdr Sabir¹*, Nabaz R. Khwarahm², Shakhawan M. Ali³, Hayman J Abdoul⁴, Kochar I. Mahmood⁵, Rimantas Kodzius^6,7*

¹Department of Medical Laboratory Sciences, Charmo University, 46023 Chamchamal, Kurdistan Region, Iraq

²Department of Biology, College of Education, University of Sulaimani, Sulaimani, Kurdistan Region, Iraq

³Department of Oral and Maxillofacial Surgery, School of Medicine, Faculty of Dentistry, University of Sulaimani,Sulaimani, Kurdistan Region, Iraq

⁴Department of Pharmaceutical Chemistry, Charmo University, 46023 Chamchamal, Kurdistan Region, Iraq

⁵Charmo Centre for Research, Training and Consultancy, Charmo University, 46023 Chamchamal, Kurdistan Region, Iraq

⁶Kaunas Technology University (KTU), 37164 Panevezys, Lithuania

⁷Ludwig Maximilian University of Munich (LMU), 80539 Munich, Germany

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is a novel strain of coronavirus that is recently identified as an etiological agent for the current pandemic respiratory illness called coronavirus disease 2019 (COVID-19). The disease might have a zoonotic origin and has infected > 19 million people around the globe with > 700,000 deaths. The published data indicate that children are generally less susceptible to contracting COVID-19. Here, we are providing a review on current hypotheses that have tried to explain the low mortality and morbidity rate among children. We believe that understanding the immunological base of children’s protection can prevent further spread of the disease.

Paola Roxana Lev^1,2, Nora Paula Goette¹, Rosana Fernanda Marta^1,2*

¹Institute of Medical Research A. Lanari, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina

²Department of Hematology Research, Institute of Medical Research (IDIM), National Scientific and Technical Research Council (CONICET), University of Buenos Aires, Buenos Aires, Argentina

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by the decrease in peripheral blood platelet count below 100 x 10⁹/L, and an increased bleeding risk when thrombocytopenia drops below 30 x 10⁹/L. The mechanisms leading to ITP in adults, although not completely elucidated, involves an imbalance between effector and regulatory cells that results in a breakdown of the immune tolerance. Autoantibodies are considered the main responsible for thrombocytopenia, although direct T-cell cytotoxic effect and lysis by Complement attachment and activation could also contribute to platelet elimination from circulation. In addition to increased peripheral clearance, abnormalities in platelet production also favors platelet count reduction. This review is intended to describe some specific knowledge about peripheral and bone marrow mechanisms leading to thrombocytopenia in adult ITP.

Rowland Utulu¹*, Joseph Urang³, Aishat Usman^1,2, Neni Aworabhi¹, Ugochukwu Osigwe², Muhammad Shakir Balogun^1,2, Eniola A. Bamgboye⁴

¹Nigeria Field Epidemiology and Laboratory Training Program

²African Field Epidemiology Network (AFENET), Abuja

³Rivers State Primary Healthcare Management Board, Port-Harcourt, Rivers state, Nigeria

⁴Department of epidemiology and medical statistics, faculty of public health, University of Ibadan, Nigeria

Background: WHO African region set a target for elimination of measles by 2020 and recommended member states adopt a case-based surveillance system. WHO AFRO guidelines for measles surveillance state that an optimally performing surveillance system is crucial to elimination of measles. Rivers State is one of the high burden states for measles in southern Nigeria.

Objective: This study assessed the performance of the measles case-based surveillance in Rivers state, Nigeria.

Methods: We reviewed measles case-based surveillance data in Rivers state, Nigeria from year 2011-2018.

Results: A total of 1,731 suspected cases were reported with 1,128 (65.2%) confirmed cases of measles. Majority were confirmed by epidemiologic linkage 907 (80.4%) while laboratory confirmed cases constituted 206 (18.3%). Age group 1-4 years was the most affected 443 (42.6%). For cases with vaccination status available 425 (53.1%) were unvaccinated. No discarded cases were reported from 2016 to 2018. Non-measles febrile rash illness rate target of ≥2 per 100,000 was not achieved at any point in the eight-year period. The proportion of districts/LGAs reporting >2 Non Measles-Non Rubella Febrile Rash Illness cases/year was above the minimum target of 80% in just four years.

Conclusion: The surveillance system performed poorly with sensitivity and representativeness less than optimal. Measles elimination must leverage upon existing structures for polio elimination to improve surveillance. A more detailed analysis of the system is essential to identify all the gaps that may retard elimination efforts.

Hlaing Nwe Thynn, Xiao-Feng Chen, Shan-Shan Dong, Yan Guo, Tie-Lin Yang*

Key Laboratory of Biomedical Information Engineering of Ministry of Education, Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P. R. China

Antonia I. Athanasiou*, Adamantios Athanasiou, Steven D. Spandorfer

Ronald O. Perelman and Claudia Cohen Centre for Reproductive Medicine, Weill Cornell Medicine, New York, USA

Basil Rigas¹*, Wei Huang^2,3, Robert A. Honkanen²

¹Departments of Preventive Medicine, Stony Brook University, Stony Brook, NY, 11794-8175; USA

²Departments of Ophthalmology, Stony Brook University, Stony Brook, NY, 11794-8175; USA

³Second Xiangya Hospital, Central South University, Changsha, Hunan, CN, China

Elisa Claeys, Kurt Vermeire*

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium

Organ transplantation is a life-saving therapeutic intervention that contributes to a better quality of life in patients with end-stage organ failure. Drastically improved outcome after organ transplantation occurred with the discovery and use of immunosuppressive drugs to prevent or treat allograft rejection. Development of several immunosuppressive agents offers the option for a multidrug approach with non-overlapping toxicities. Still, the side effects of these agents can be severe, resulting in a shorter life expectancy for transplant patients compared to the general population. Therefore, the development of new immunosuppressive therapies that promote immune tolerance without the side effects observed today is needed. In this review, we will discuss the mechanism of allograft rejection as well as the mode of action and side effects of currently used immunosuppressive agents.

Abbreviations

APC, antigen-presenting cell; ATG, antithymocyte globulin; IL, interleukin; MHC, major histocompatibility complex; MMF, mycophenolate mofetil; mTOR, mammalian target of rapamycin; NFAT, nuclear factor of activated T cells; Th, T helper; Treg, regulatory T