scholarly journals Inborn errors of immunity to infection

2005 ◽  
Vol 202 (2) ◽  
pp. 197-201 ◽  
Author(s):  
Jean-Laurent Casanova ◽  
Laurent Abel
Keyword(s):  
Immune System ◽  
Natural Selection ◽  
Life Expectancy ◽  
Infectious Diseases ◽  
Life Span ◽  
Human Life ◽  
Human History ◽  
Inborn Errors ◽  
Inborn Errors Of Immunity ◽  
Human Life Span

The immune system's function is to protect against microorganisms, but infection is nonetheless the most frequent cause of death in human history. Until the last century, life expectancy was only ∼25 years. Recent increases in human life span primarily reflect the development of hygiene, vaccines, and anti-infectious drugs, rather than the adjustment of our immune system to coevolving microbes by natural selection. We argue here that most individuals retain a natural vulnerability to infectious diseases, reflecting a great diversity of inborn errors of immunity.

scholarly journals Is Financial Inclusion a Determinant of Life Expectancy? Evidence from West African Region

2021 ◽  
Vol 23 (1) ◽  
pp. 22-37
Author(s):  
Aderopo Raphael Adediyan
Keyword(s):  
Life Expectancy ◽  
Life Span ◽  
Financial Services ◽  
Human Life ◽  
Production Quality ◽  
West African ◽  
Financial Inclusion ◽  
African Region ◽  
African Countries ◽  
Human Life Span

This study is a contribution to the debate on the significance of financial inclusion with much emphasis on its impacts on human life span. The sample used for the analyses consisted of 14 West African countries over the period 2010 and 2018. The study employed a dynamic 2-Step System GMM approach, and under different model specifications, control for public and private health expenditure, food production quality, population, access to electricity, and the number of people practicing open defecation. The estimated results, among others, showed considerable evidence of positive feedback of financial inclusion on human life span. As such, substantial improvement in the access to and use of financial services is key to a high life expectancy in the region.

Is Human DNA Special?

2020 ◽  
pp. 83-99
Author(s):  
Alan McHughen
Keyword(s):  
Life Span ◽  
Human Evolution ◽  
Human Life ◽  
Human Beings ◽  
Human History ◽  
Genetic Purity ◽  
Human Dna ◽  
Use Of Technology ◽  
Genetic Features ◽  
Human Life Span

Chapter 3 explores “Human DNA” and the genetic features of human beings. Genetic inheritance in humans follows the same patterns and principles as those of other animals and plants, but far more scientists have studied humans than have studied any other species. Thus, scientists have accumulated a hugely disproportionate amount of information directly relevant to humans. This chapter examines some curious features of human evolution. Is there a genetic basis for human race and genetic “purity”? Are telomeres ticking time bombs inside cells limiting the human life span? How did most humans end up with Neanderthal DNA in their genomes? It’s just the way the DNA cookie crumbles. This chapter also introduces the use of technology based on DNA, from human DNA fingerprinting to probing human history.

scholarly journals Inborn errors of immunity—recent advances in research on the pathogenesis

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Motoi Yamashita ◽  
Kento Inoue ◽  
Tsubasa Okano ◽  
Tomohiro Morio
Keyword(s):  
Immune System ◽  
Hematopoietic Cell Transplantation ◽  
Epigenetic Modification ◽  
Genetic Disorder ◽  
Loss Of Function ◽  
Inborn Errors ◽  
Whole Genome Analysis ◽  
Curative Therapy ◽  
Inborn Errors Of Immunity ◽  
Recent Advances

AbstractPrimary immunodeficiency (PID) is a genetic disorder with a defect of one of the important components of our immune system. Classical PID has been recognized as a disorder with loss of function of the immune system. Recent studies have unveiled disorders with immune dysfunction with autoimmunity, autoinflammation, allergy, or predisposition to malignancy. Some of them were caused by an augmented immune function or a defect in immune regulation. With this background, the term inborn errors of immunity (IEI) is now used to refer to PID in the International Union of Immunological Societies (IUIS) classification. More than 400 responsible genes have been identified in patients with IEI so far, and importantly, many of them identified lately were caused by a heterologous mutation. Moreover, the onset is not necessarily in childhood, and we started seeing more and more IEI patients diagnosed in adulthood in the clinical settings. Recent advances in genetic analysis, including whole-exome analysis, whole-genome analysis, and RNA-seq have contributed to the identification of the disease-causing gene mutation. We also started to find heterogeneity of phenotype even in the patients with the same mutation in the same family, leading us to wonder if modifier gene or epigenetic modification is involved in the pathogenesis. In contrast, we accumulated many cases suggesting genetic heterogeneity is associated with phenotypic homogeneity. It has thus become difficult to deduce a responsible gene only from the phenotype in a certain type of IEI. Current curative therapy for IEI includes hematopoietic cell transplantation and gene therapy. Other curative therapeutic modalities have been long waited and are to be introduced in the future. These include a small molecule that inhibits the gain-of-function of the molecule- and genome-editing technology. Research on IEI will surely lead to a better understanding of other immune-related disorders including rheumatic diseases and atopic disorders.

Role of Flow Cytometry in the Diagnosis of Inborn Errors of Immunity

2022 ◽  
Author(s):  
Thulasi Raman Ramalingam
Keyword(s):  
Flow Cytometry ◽  
Immune System ◽  
B Lymphocyte ◽  
Molecular Genetic ◽  
Clinical History ◽  
Final Diagnosis ◽  
Inborn Errors ◽  
Reliable Technique ◽  
Humoral Immunodeficiency ◽  
Inborn Errors Of Immunity

AbstractInborn errors of immunity (IEI) are a group of inherited heterogeneous disorders affecting the immune system characterized by increased susceptibility to infections, immune dysregulation, and lymphoproliferation. Flow cytometry (FCM) is a rapid and reliable technique for evaluation and enumeration of immune cells. It also helps in understanding the functional and signaling pathways of the immune system. Lymphocyte subset analysis is a simple and effective screening tool in suspected combined and humoral immunodeficiency patients. Qualitative phagocytic defects such as chronic granulomatous disease and leucocyte adhesion defect are easily diagnosed by FCM. Study of intracellular proteins (e.g., BTK, WASP, DOCK8), cytokine production, and signaling molecules (e.g., STAT3) by FCM is very useful but also quite challenging to establish. T and B lymphocyte interaction for normal class switching of B cells can be assessed and can help in diagnosis of combined variable immunodeficiency and hyperimmunoglobulin M syndrome. FCM is also used in posttransplant monitoring of IEI patients and also in prenatal diagnosis in suspected cases. It is also useful in validation of variants of uncertain significance obtained in exome sequencing. FCM results should always be interpreted with clinical history and, if needed, should be confirmed with molecular genetic studies before establishing the final diagnosis. Ensuring good sample quality and running parallel controls with patient samples will avoid the preanalytical and analytical errors. This review describes the applications of FCM in the diagnosis of various IEI.

scholarly journals Lethal Infectious Diseases as Inborn Errors of Immunity: Toward a Synthesis of the Germ and Genetic Theories

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Jean-Laurent Casanova ◽  
Laurent Abel
Keyword(s):  
Infectious Diseases ◽  
20Th Century ◽  
Mendelian Inheritance ◽  
Annual Review ◽  
Publication Date ◽  
Recurrent Infections ◽  
Late 19Th Century ◽  
Inborn Errors ◽  
Inborn Errors Of Immunity ◽  
Classical Genetics

It was first demonstrated in the late 19th century that human deaths from fever were typically due to infections. As the germ theory gained ground, it replaced the old, unproven theory that deaths from fever reflected a weak personal or even familial constitution. A new enigma emerged at the turn of the 20th century, when it became apparent that only a small proportion of infected individuals die from primary infections with almost any given microbe. Classical genetics studies gradually revealed that severe infectious diseases could be driven by human genetic predisposition. This idea gained ground with the support of molecular genetics, in three successive, overlapping steps. First, many rare inborn errors of immunity were shown, from 1985 onward, to underlie multiple, recurrent infections with Mendelian inheritance. Second, a handful of rare and familial infections also segregating as Mendelian traits but striking humans resistant to other infections were deciphered molecularly from 1996 onward. Third, a growing number of rare or common sporadic infections were shown to result from monogenic, but not Mendelian, inborn errors from 2007 onward. A synthesis of the hitherto mutually exclusive germ and genetic theories is now in view. This article has been accepted for publication on April 14, 2020. Changes may still occur before final publication. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 16 is January 24, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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