Understanding the genetic and epigenetic basis of common variable immunodeficiency disorder through omics approaches

Jin, Li; Wei, Zhi; Li, Yun R.; Maggadóttir, Sólrún Melkorka; Chang, Xiao; Desai, Akshatha; Hákonarson, Hákon

doi:10.1016/j.bbagen.2016.06.014

Cited by 25 publications

(19 citation statements)

References 69 publications

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“…The wide spectrum of immunological presentations of PAD constitutes B-cell lymphopenia, agammaglobulinemia, hyper-IgM syndrome, hypogammaglobulinemia, isotype deficiencies as well as a transient form of a humoral immunodeficiency (Figure 1). Several mutations in PAD patients that play key roles in B-cell activation, proliferation, differentiation, classswitch recombination, somatic hypermutation and apoptosis have been identified; however, the etiology remains unknown in a majority of the patients [4,[6][7][8][9][10].…”

Section: List Of Abbreviationsmentioning

confidence: 99%

Clinical implications of systematic phenotyping and exome sequencing in patients with primary antibody deficiency

Abolhassani

Aghamohammadi

Fang

et al. 2019

Genetics in Medicine

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Section: List Of Abbreviationsmentioning

confidence: 99%

Clinical implications of systematic phenotyping and exome sequencing in patients with primary antibody deficiency

Abolhassani

Aghamohammadi

Fang

et al. 2019

Genetics in Medicine

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“…Assuming that CVID endotypes present within these phenotypic clusters, the pathogenesis and genetic mechanisms underlying the disease may be related. Autoimmunity and immune deficiency have been shown to have genetic overlap and occur together beyond CVID (18)(19)(20), suggesting a common pathophysiologic mechanism underlying both forms of immune dysregulation. In this review, we focus on one aspect of immune dysregulation, the autoimmune manifestations of CVID, providing an overview of these complications as well as an update on research and treatment advances.…”

Section: Introductionmentioning

confidence: 99%

Current Understanding and Recent Developments in Common Variable Immunodeficiency Associated Autoimmunity

Gereige

Maglione

2019

Front. Immunol.

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Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency and comprises a group of disorders with similar antibody deficiency but a myriad of different etiologies, most of which remain undefined. The variable aspect of CVID refers to the approximately half of patients who develop non-infectious complications in addition to heightened susceptibility to infection. The pathogenesis of these complications is poorly understood and somewhat counterintuitive because these patients that are defined by their immune futility simultaneously have elevated propensity for autoimmune disease. There are numerous aspects of immune dysregulation associated with autoimmunity in CVID that have only begun to be studied. These findings include elevations of T helper type 1 and follicular helper T cells and B cells expressing low levels of CD21 as well as reciprocal decreases in regulatory T cells and isotype-switched memory B cells. Recently, advances in genomics have furthered our understanding of the fundamental biology underlying autoimmunity in CVID and led to precision therapeutic approaches. However, these genetic etiologies are also associated with clinical heterogeneity and incomplete penetrance, highlighting the fact that continued research efforts remain necessary to optimize treatment. Additional factors, such as commensal microbial dysbiosis, remain to be better elucidated. Thus, while recent advances in our understanding of CVID-associated autoimmunity have been exciting and substantial, these current scientific advances must now serve as building blocks for the next stages of discovery.

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“…Systems immunology and epigenomics are emerging fields that may greatly advance our current understanding of human immunology during health and disease ( 12 , 54 , 105 , 106 ). Longitudinal birth cohort studies that combine cutting-edge multidimensional approaches in epigenetics and immunology are needed to establish the timing, critical checkpoints and early exposures determining non-heritable variability in specific bone marrow-derived and peripheral immune cell populations and functions as well as immune responses in epithelial cells and other key components of the mucosal barriers in humans.…”

Section: Future Directionsmentioning

confidence: 99%

Epigenomics and Early Life Human Humoral Immunity: Novel Paradigms and Research Opportunities

et al. 2020

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The molecular machinery controlling immune development has been extensively investigated. Studies in animal models and adult individuals have revealed fundamental mechanisms of disease and have been essential to understanding how humans sense and respond to cellular stress, tissue damage, pathogens and their environment. Nonetheless, our understanding of how immune responses originate during human development is just starting to emerge. In particular, studies to unveil how environmental and other non-heritable factors shape the immune system at the beginning of life offer great promise to yield important knowledge about determinants of normal inter-individual immune variation and to prevent and treat many human diseases. In this review, we summarize our current understanding of some of the mechanisms determining early life antibody production as a model of an immune process with sequential molecular checkpoints susceptible to influence by non-heritable factors. We discuss the potential of epigenomics as a valuable approach that may reveal not only relevant gene-environment interactions but important clues about immune developmental processes and homeostasis in early life. We then highlight the novel paradigm of human immunology as a complex field that nowadays requires a longitudinal systems-biology approach to understand normal variation and developmental changes during the first few years of life.

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Understanding the genetic and epigenetic basis of common variable immunodeficiency disorder through omics approaches

Cited by 25 publications

References 69 publications

Clinical implications of systematic phenotyping and exome sequencing in patients with primary antibody deficiency

Clinical implications of systematic phenotyping and exome sequencing in patients with primary antibody deficiency

Current Understanding and Recent Developments in Common Variable Immunodeficiency Associated Autoimmunity

Epigenomics and Early Life Human Humoral Immunity: Novel Paradigms and Research Opportunities

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