scholarly journals Hypothetical COVID-19 protection mechanism: hints from centenarians

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Franca Rosa Guerini ◽  
Matteo Cesari ◽  
Beatrice Arosio
Keyword(s):  
Adaptive Immune Response ◽  
Human Leukocyte ◽  
Human Longevity ◽  
Biological Mechanisms ◽  
Protection Mechanism ◽  
Leukocyte Antigen ◽  
Adaptive Immune ◽  
Life Threatening ◽  
Coronavirus Infection ◽  
Rule Out

AbstractThe risk of serious complications and the fatality rate due to COVID-19 pandemic have proven particularly higher in older persons, putting a further strain in healthcare system as we dramatically observed.COVID-19 is not exclusively gerophile (géro “old” and philia “love”) as young people can be infected, even if older people experience more severe symptoms and mortality due to their greater frailty. Indeed, frailty could complicate the course of COVID-19, much more than the number of years lived. As demonstration, there are centenarians showing remarkable capacity to recover after coronavirus infection.We hypothesize that centenarian’s portfolio could help in identifying protective biological mechanisms underlying the coronavirus infection.The human leukocyte antigen (HLA) is one of the major genetic regions associated with human longevity, due to its central role in the development of adaptive immune response and modulation of the individual’s response to life threatening diseases. The HLA locus seems to be crucial in influencing susceptibility and severity of COVID-19.In this hypothesis, we assume that the biological process in which HLA are involved may explain some aspects of coronavirus infection in centenarians, although we cannot rule out other biological mechanisms that these extraordinary persons are able to adopt to cope with the infection.

Narcolepsy: Differential Diagnosis or Etiology in Some Cases of Bipolar Disorder and Schizophrenia?

CNS Spectrums ◽  
2003 ◽  
Vol 8 (2) ◽  
pp. 120-126 ◽  
Author(s):  
Alan B. Douglass
Keyword(s):  
Bipolar Disorder ◽  
Differential Diagnosis ◽  
Psychiatric Patients ◽  
Human Leukocyte ◽  
Sleep Paralysis ◽  
Leukocyte Antigen ◽  
Psychotic Features ◽  
Hypnagogic Hallucinations ◽  
Rule Out

AbstractDoes narcolepsy, a neurological disease, need to be considered when diagnosing major mental illness? Clinicians have reported cases of narcolepsy with prominent hypnagogic hallucinations that were mistakenly diagnosed as schizophrenia. In some bipolar disorder patients with narcolepsy, the HH resulted in their receiving a more severe diagnosis (ie, bipolar disorder with psychotic features or schizoaffective disorder). The role of narcolepsy in psychiatric patients has remained obscure and problematic, and it may be more prevalent than commonly believed. Classical narcolepsy patients display the clinical “tetrad”—cataplexy, hypnagogic hallucinations, daytime sleep attacks, and sleep paralysis. Over 85% also display the human leukocyte antigen marker DQB10602 (subset of DQ6). Since 1998, discoveries in neuroanatomy and neurophysiology have greatly advanced the understanding of narcolepsy, which involves a nearly total loss of the recently discovered orexin/hypocretin (hypocretin) neurons of the hypothalamus, likely by an autoimmune mechanism. Hypocretin neurons normally supply excitatory signals to brainstem nuclei producing norepinephrine, serotonin, histamine, and dopamine, with resultant suppression of sleep. They also project to basal forebrain areas and cortex. A literature review regarding the differential diagnosis of narcolepsy, affective disorder, and schizophrenia is presented. Furthermore, it is now possible to rule out classical narcolepsy in difficult psychiatric cases. Surprisingly, psychotic patients with narcolepsy will likely require stimulants to fully recover. Many conventional antipsychotic drugs would worsen their symptoms and make them appear to become a “chronic psychotic,” while in fact they can now be properly diagnosed and treated.

scholarly journals Toxic epidermal necrolysis

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 951 ◽  
Author(s):  
Wolfram Hoetzenecker ◽  
Tarun Mehra ◽  
Ieva Saulite ◽  
Martin Glatz ◽  
Peter Schmid-Grendelmeier ◽  
...  
Keyword(s):  
Cell Death ◽  
Mortality Rate ◽  
Toxic Epidermal Necrolysis ◽  
Human Leukocyte ◽  
Best Supportive Care ◽  
Drug Induced ◽  
Leukocyte Antigen ◽  
Mucosal Involvement ◽  
Keratinocyte Cell ◽  
Life Threatening

Toxic epidermal necrolysis (TEN) is a rare, life-threatening drug-induced skin disease with a mortality rate of approximately 30%. The clinical hallmark of TEN is a marked skin detachment caused by extensive keratinocyte cell death associated with mucosal involvement. The exact pathogenic mechanism of TEN is still uncertain. Recent advances in this field have led to the identification of several factors that might contribute to the induction of excessive apoptosis of keratinocytes. In addition, specific human leukocyte antigen types seem to be associated with certain drugs and the development of TEN. As well-controlled studies are lacking, patients are treated with various immunomodulators (e.g. intravenous immunoglobulin) in addition to the best supportive care.

scholarly journals Epidemiological Profile of COVID-19 in Brazil and Worldwide

2021 ◽  
Vol 9 (2) ◽  
Author(s):  
Carla De Freitas ◽  
Gabriela Calanca ◽  
Elias Jirjoss Ilias ◽  
Arthur Sousa Bezerra
Keyword(s):  
High Capacity ◽  
Adaptive Immune Response ◽  
Hormonal Changes ◽  
Age Group ◽  
Health It ◽  
Susceptibility To Infection ◽  
Adaptive Immune ◽  
Fourth Decade ◽  
Coronavirus Infection ◽  
Epidemiological Profile

Introduction: COVID-19, caused by the new coronavirus or SARSCoV-2, has a high capacity for dissemination, which brings about an emergency scenario in public health. It manifests itself in a multifaceted manner, with a great variability in the profile of the affected population, which may be associated with biological, social and economic factors. Objective: To know the epidemiological profile of the population affected by COVID-19, in order to promote better assistance.   Methods: This is a literature review, starting in 2020, using the SciELO, PubMed, Google Scholar, DATASUS databases and the website of the Brazilian Institute of Geography and Statistics (IBGE).   Results: Studies show a higher prevalence of SARS-CoV-2 infection in men, in the age group after the fourth decade of life and among whites.   Discussion: The first studies showed a prevalence of coronavirus infection in males. One of the hypotheses drawn was that men present more cardiopulmonary diseases and smoke more. Another study shows that women's lower susceptibility to infection is due to the X chromosome and sex hormones, which are essential for the innate and adaptive immune response. As for the age group, most studies show a higher prevalence after the fourth decade of life, due to increased expression of angiotensin 2 receptors (ACE2), hormonal changes in aging and associated comorbidities.   Conclusion: Studies show with greater assertiveness a predominance of involvement by COVID-19 in males, individuals from the fourth decade of life and in whites. However, it is important to investigate the epidemiological profile in order to offer better assistance and prevention.

scholarly journals Protective effects of HLA-DRB1*04 subtypes in Parkinson's and Alzheimer's diseases implicate acetylated Tau PHF6 sequences

2021 ◽  
Author(s):  
Yann Le Guen ◽  
Guo Luo ◽  
Aditya Ambati ◽  
Vincent Damotte ◽  
Iris Jansen ◽  
...  
Keyword(s):  
Adaptive Immune Response ◽  
Human Leukocyte ◽  
Postmortem Brain ◽  
Neuritic Plaque ◽  
Protective Effects ◽  
Hla Association ◽  
Leukocyte Antigen ◽  
Genome Wide ◽  
Association Data ◽  
Lateral Sclerosis

Using genome-wide association data, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's (PD) or Alzheimer's (AD) disease versus controls across ancestry groups. A shared genetic association was observed across diseases at rs601945 (PD: odds ratio (OR)=0.84; 95% confidence interval, [0.80; 0.88]; p=2.2x10-13; AD: OR=0.91[0.89; 0.93]; p=1.8x10-22), and with a protective HLA association recently reported in amyotrophic lateral sclerosis (ALS). Hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03, and absent for HLA-DRB1*04:05. The same signal was associated with decreased neurofibrillary tangles (but not neuritic plaque density) in postmortem brain and was more strongly associated with Tau levels than Aβ42 levels in the cerebrospinal fluid. Finally, protective HLA-DRB1*04 subtypes strongly bound aggregation-prone Tau PHF6 sequence, but only when acetylated at K311, a modification central to aggregation. A HLA-DRB1*04-mediated adaptive immune response, potentially against Tau, decreases PD, AD and ALS risk, offering the possibility of new therapeutic avenues.

scholarly journals The Interplay between Host Defense, Infection, and Clinical Status in Septic Patients: A Narrative Review

2022 ◽  
Vol 23 (2) ◽  
pp. 803
Author(s):  
Alessandro Lazzaro ◽  
Gabriella De Girolamo ◽  
Valeria Filippi ◽  
Giuseppe Pietro Innocenti ◽  
Letizia Santinelli ◽  
...  
Keyword(s):  
Clinical Status ◽  
Adaptive Immune Response ◽  
Narrative Review ◽  
Burn Patients ◽  
Adaptive Immune ◽  
Threatening Condition ◽  
Recent Developments ◽  
Life Threatening ◽  
Diagnostic Approaches ◽  
The Complement System

Sepsis is a life-threatening condition that arises when the body’s response to an infection injures its own tissues and organs. Despite significant morbidity and mortality throughout the world, its pathogenesis and mechanisms are not clearly understood. In this narrative review, we aimed to summarize the recent developments in our understanding of the hallmarks of sepsis pathogenesis (immune and adaptive immune response, the complement system, the endothelial disfunction, and autophagy) and highlight novel laboratory diagnostic approaches. Clinical management is also discussed with pivotal consideration for antimicrobic therapy management in particular settings, such as intensive care unit, altered renal function, obesity, and burn patients.

scholarly journals Convalescent Plasma: A Potential Treatment for COVID-19

2020 ◽  
pp. 109-115
Author(s):  
Mohiuddin Ahmed Khan ◽  
Mafruha Akter
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Infections ◽  
Adaptive Immune Response ◽  
Case Series ◽  
Severe Illness ◽  
Neutralization Activity ◽  
Adaptive Immune ◽  
Life Threatening Illness ◽  
Life Threatening ◽  
Specific Standard

As no specific standard therapies have been approved for Coronavirus disease 2019 (COVID-19), so prevention and supportive care dominate the approach to COVID-19. Exposure to this severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in an adaptive immune response that commonly include antibodies with neutralization activity. Treatments directly targeting the virus and the inflammatory response to it remain investigational. Convalescent plasma (CP) is such a therapy that had been reported hundred years back in studies from the Spanish influenza era. So the idea of convalescent plasma from subjects who have recovered from viral infections has been used to both prevent or treat disease. Over the past two decades’ notable examples of the successful use of convalescent plasma (CP) include influenza, measles, Middle East respiratory syndrome (MERS), Ebola and severe acute respiratory syndrome (SARS). Two case series were recently published by China examining the therapeutic use of CP in patients with COVID-19. In the context of pandemic situation, the Food and Drug Administration (FDA) allowed to use COVID-19 convalescent plasma as Investigational New Drug (IND) since April 2020 to help patients with serious or immediately life-threatening illness associated with COVID- 19. Case series studying convalescent plasma use in the treatment of COVID-19 have been promising, but additional, high-quality studies are needed to determine the efficacy of the treatment when applied for prophylaxis, for early phases of illness and for severe illness. Bangladesh also started program to use convalescent plasma for severe and critical COVID-19 patients under limited clinical trial. J Bangladesh Coll Phys Surg 2020; 38(0): 109-115

scholarly journals HLA Immune Function Genes in Autism

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Anthony R. Torres ◽  
Jonna B. Westover ◽  
Allen J. Rosenspire
Keyword(s):  
Immune Responses ◽  
Autoimmune Diseases ◽  
Human Leukocyte ◽  
Chromosome 6 ◽  
Genetic Studies ◽  
Leukocyte Antigen ◽  
Adaptive Immune ◽  
Hla Genes ◽  
Genetic Complexity ◽  
Antigen Presenting

The human leukocyte antigen (HLA) genes on chromosome 6 are instrumental in many innate and adaptive immune responses. The HLA genes/haplotypes can also be involved in immune dysfunction and autoimmune diseases. It is now becoming apparent that many of the non-antigen-presenting HLA genes make significant contributions to autoimmune diseases. Interestingly, it has been reported that autism subjects often have associations with HLA genes/haplotypes, suggesting an underlying dysregulation of the immune system mediated by HLA genes. Genetic studies have only succeeded in identifying autism-causing genes in a small number of subjects suggesting that the genome has not been adequately interrogated. Close examination of the HLA region in autism has been relatively ignored, largely due to extraordinary genetic complexity. It is our proposition that genetic polymorphisms in the HLA region, especially in the non-antigen-presenting regions, may be important in the etiology of autism in certain subjects.

scholarly journals TLR Agonists as Vaccine Adjuvants Targeting Cancer and Infectious Diseases

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 142
Author(s):  
Marina Luchner ◽  
Sören Reinke ◽  
Anita Milicic
Keyword(s):  
Immune Response ◽  
Transmembrane Domain ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Vaccine Adjuvants ◽  
Transmembrane Receptors ◽  
Tlr Agonists ◽  
Adaptive Immune ◽  
Endosomal Membranes ◽  
Life Threatening

Modern vaccines have largely shifted from using whole, killed or attenuated pathogens to being based on subunit components. Since this diminishes immunogenicity, vaccine adjuvants that enhance the immune response to purified antigens are critically needed. Further advantages of adjuvants include dose sparing, increased vaccine efficacy in immunocompromised individuals and the potential to protect against highly variable pathogens by broadening the immune response. Due to their ability to link the innate with the adaptive immune response, Toll-like receptor (TLR) agonists are highly promising as adjuvants in vaccines against life-threatening and complex diseases such as cancer, AIDS and malaria. TLRs are transmembrane receptors, which are predominantly expressed by innate immune cells. They can be classified into cell surface (TLR1, TLR2, TLR4, TLR5, TLR6) and intracellular TLRs (TLR3, TLR7, TLR8, TLR9), expressed on endosomal membranes. Besides a transmembrane domain, each TLR possesses a leucine-rich repeat (LRR) segment that mediates PAMP/DAMP recognition and a TIR domain that delivers the downstream signal transduction and initiates an inflammatory response. Thus, TLRs are excellent targets for adjuvants to provide a “danger” signal to induce an effective immune response that leads to long-lasting protection. The present review will elaborate on applications of TLR ligands as vaccine adjuvants and immunotherapeutic agents, with a focus on clinically relevant adjuvants.

scholarly journals A case of SARS-CoV-2 reinfection in a patient with obstructive sleep apnea managed with telemedicine

2021 ◽  
Vol 14 (2) ◽  
pp. e240496
Author(s):  
Isabelo Sicsic Jr ◽  
Andres R Chacon ◽  
Moe Zaw ◽  
Kori Ascher ◽  
Alexandre Abreu ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Acute Infection ◽  
Adaptive Immune Response ◽  
The Novel ◽  
Adaptive Immune ◽  
Obstructive Sleep ◽  
Coronavirus Infection ◽  
Novel Coronavirus

The novel coronavirus (SARS-CoV-2) has produced millions of infections and deaths worldwide. It is believed that adaptive immunity to the virus occurs although with variation in its pattern and duration. While uncommon, confirmed reinfection with the novel coronavirus has been reported. Telemedicine has emerged as a viable tool for the delivery of healthcare in lieu of in-person patient contact. The variable and occasionally rapid course of clinical disease raises safety concerns of using telemedicine in the clinical management of acute infection with the novel coronavirus. We present a case of novel coronavirus infection in an immunocompetent individual with obstructive sleep apnea (OSA) who failed to manifest an adaptive immune response to acute infection and was subsequently reinfected. The case highlights the use of telemedicine in managing novel coronavirus respiratory disease and the potential role of OSA as a disease facilitator.

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