scholarly journals The role of HLA genes: from autoimmune diseases to COVID-19

2020 ◽  
Vol 66 (4) ◽  
pp. 9-15
Author(s):  
Ekaterina A. Troshina ◽  
Marina Yu. Yukina ◽  
Nurana F. Nuralieva ◽  
Natalia G. Mokrysheva
Keyword(s):  
Immune System ◽  
Autoimmune Diseases ◽  
Genetic Predisposition ◽  
Human Leukocyte ◽  
Normal Functioning ◽  
Leukocyte Antigen ◽  
Hla Genes ◽  
Histocompatibility Complex ◽  
Hla Molecules

Genes of HLA system (Human Leukocyte Antigen) play an essential role in the normal functioning of the immune system. There are three classes of genes: I, II, and III. The function of HLA molecules class I is to present antigens of peptides from the cytoplasm to T-lymphocytes on the cell surface, and class II — to present antigens of peptides from the extracellular space. In the classical view, the pathological activation of the immune system in patients with a genetic predisposition can result in the development of autoimmune diseases. However, the influence of this system on the development of non-autoimmune diseases, their severity and prognosis, has been recently considered. Besides, HLA molecules provide a presentation of various infectious agents. In this connection, the loci of the main histocompatibility complex can be considered candidates for determining the genetic predisposition to infectious diseases themselves and their course. This review hypothesizes that specific variants of HLA genes may cause the formation of a «cytokine storm» in patients with COVID-19. Identification of a group of patients with particular genetic variations that cause violation of immune tolerance and hyperresponse in the setting of viral infection will help to optimize the algorithm for disease prevention and treatment of such patients and, as a result, to reduce the severity of the epidemiological situation.

scholarly journals Familial Pemphigus Vulgaris Occured in a Father and Son as the First Confirmed Cases

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Ali Haydar Eskiocak ◽  
Birgul Ozkesici ◽  
Soner Uzun
Keyword(s):  
Genetic Predisposition ◽  
Human Leukocyte ◽  
Pemphigus Vulgaris ◽  
Hla Typing ◽  
Enzyme Linked Immunosorbent Assay ◽  
Leukocyte Antigen ◽  
Hla Genes ◽  
Mother And Daughter ◽  
First Occurrence ◽  
Father And Son

Pemphigus vulgaris (PV) is a chronic autoimmune bullous disease of the skin and mucous membranes. Although there is some evidence pointing towards a genetic predisposition by some human leukocyte antigen (HLA) genes, familial occurrence of PV is very rare. Most of the familial PV cases so far reported have been in mother and daughter and in siblings. PV in father and son, as presented here, has not been reported in the literature before, except an unconfirmed report. The diagnosis of PV was established by histologic, cytologic studies and enzyme linked immunosorbent assay (ELISA) in Case1and by ELISA and BIOCHIP indirect immunofluorescence test in Case2. The son was responsive to moderate doses of methylprednisolone, with the treatment continuing with tapered doses. The father was in a subclinic condition; consequently, only close follow-up was recommended. HLA typing studies revealed identical HLA alleles of HLA-DR4 (DRB1⁎04) and HLA-DQB1⁎03in both of our cases; this had been found to be associated with PV in prior studies. Familial occurrences of PV and related HLA genes indicate the importance of genetic predisposition. The first occurrence of confirmed familial PV in father and son is reported here.

scholarly journals Role of Human Leukocyte Antigens at the Feto-Maternal Interface in Normal and Pathological Pregnancy: An Update

2020 ◽  
Vol 21 (13) ◽  
pp. 4756
Author(s):  
Chiara Tersigni ◽  
Federica Meli ◽  
Caterina Neri ◽  
Azzurra Iacoangeli ◽  
Rita Franco ◽  
...  
Keyword(s):  
Immune System ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Immune Recognition ◽  
Protective Mechanisms ◽  
Maternal Immune System ◽  
Hla Class I Molecules ◽  
Classical Pattern ◽  
Hla Molecules

The successful maternal tolerance of the semi-allogeneic fetus provides an apparent immunologic paradox. Indeed, deep invasion of placental trophoblast cells into maternal uterine tissue and the following growth of the fetus have to be tolerated by a pregnant woman’s immune system. Among the various possible protective mechanisms that may be involved in human pregnancy, the expression of a non-classical pattern of human leukocyte antigen (HLA) class I molecules and the complete lack of expression of HLA class II molecules in placental tissues seem to be the most relevant mechanisms of fetal escape from maternal immune recognition. The importance of HLA molecules in fetal toleration by the maternal immune system is highlighted by pregnancy complications occurring in cases of abnormal HLA molecule expression at the maternal–fetal interface. In this review, we summarize evidences about the role of placental HLA molecules in normal and pathological pregnancies.

scholarly journals Quantifying the impact of Human Leukocyte Antigen on the human gut microbiome

2020 ◽  
Author(s):  
Stijn P. Andeweg ◽  
Can Keşmir ◽  
Bas E. Dutilh
Keyword(s):  
Immune System ◽  
Gut Microbiome ◽  
Human Leukocyte ◽  
Human Gut ◽  
Microbiome Composition ◽  
Leukocyte Antigen ◽  
Human Gut Microbiome ◽  
Microbiome Diversity ◽  
Human Immune ◽  
Hla Molecules

AbstractObjectiveThe gut microbiome is affected by a number of factors, including the innate and adaptive immune system. The major histocompatibility complex (MHC), or the human leukocyte antigen (HLA) in humans, performs an essential role in vertebrate immunity, and is very polymorphic in different populations. HLA determines the specificity of T lymphocyte and natural killer (NK) cell responses, including against the commensal bacteria present in the human gut. Thus, it is likely that our HLA molecules and thereby the adaptive immune response, can shape the composition of our microbiome. Here, we investigated the effect of HLA haplotype on the microbiome composition.ResultsWe performed HLA typing and microbiota composition analyses on 3,002 public human gut microbiome datasets. We found that (i) individuals with functionally similar HLA molecules (i.e. presenting similar peptides) are also similar in their microbiota, and (ii) HLA homozygosity correlated with microbiome diversity, suggesting that diverse immune responses limit microbiome diversity.ConclusionOur results show a statistical association between host HLA haplotype and gut microbiome composition. Because the HLA haplotype is a readily measurable parameter of the human immune system, these results open the door to incorporating the immune system into predictive microbiome models.IMPORTANCEThe microorganisms that live in the digestive tracts of humans, known as the gut microbiome, are essential for hosts survival as they support crucial functions. For example, they support the host in facilitating the uptake of nutrients and give colonization resistance against pathogens. The composition of the gut microbiome varies among humans. Studies have proposed multiple factors driving the observed variation, including; diet, lifestyle, and health condition. Another major influence on the microbiome is the host’s genetic background. We hypothesized the immune system to be one of the most important genetic factors driving the differences observed between gut microbiomes. Therefore, we are interested in linking the polymorphic molecules that play a role in human immune responses to the composition of the microbiome. HLA molecules are the most polymorphic molecules in our genome and therefore makes an excellent candidate to test such an association/link. To our knowledge for the first time, our results indicate a significant impact of the HLA on the human gut microbiome composition.

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 The HLA-G Immune Checkpoint Plays a Pivotal Role in the Regulation of Immune Response in Autoimmune Diseases

2021 ◽  
Vol 22 (24) ◽  
pp. 13348
Author(s):  
Monika Zaborek-Łyczba ◽  
Jakub Łyczba ◽  
Paulina Mertowska ◽  
Sebastian Mertowski ◽  
Anna Hymos ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Mhc Class I ◽  
Hematologic Malignancies ◽  
Leukocyte Antigen ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecule ◽  
Immunomodulatory Function

The human G-leukocyte antigen (HLA-G) molecule is a non-classical major histocompatibility complex (MHC) class I molecule. The pertinence of HLA-G has been investigated in numerous studies which have sought to elucidate the relevance of HLA-G in pathologic conditions, such as autoimmune diseases, cancers, and hematologic malignancies. One of the main goals of the current research on HLA-G is to use this molecule in clinical practice, either in diagnostics or as a therapeutic target. Since HLA-G antigens are currently considered as immunomodulatory molecules that are involved in reducing inflammatory and immune responses, in this review, we decided to focus on this group of antigens as potential determinants of progression in autoimmune diseases. This article highlights what we consider as recent pivotal findings on the immunomodulatory function of HLA-G, not only to establish the role of HLA-G in the human body, but also to explain how these proteins mediate the immune response.

scholarly journals Heredity of psoriasis

2004 ◽  
Vol 57 (3-4) ◽  
pp. 171-174
Author(s):  
Dobrila Belic ◽  
Sonja Ristic-Nikolic ◽  
Saveta Damjan ◽  
Iljana Ratkov ◽  
Matilda Ceke
Keyword(s):  
Genetic Predisposition ◽  
Human Leukocyte ◽  
Epidemiological Studies ◽  
Trigger Factor ◽  
Leukocyte Antigen ◽  
Significant Statistical Difference ◽  
Histocompatibility Complex ◽  
Hereditary Component ◽  
Relative Analysis ◽  
Structured Questionnaire

INTRODUCTION Epidemiological studies of twins show that there is a genetic predisposition to psoriasis. Researches conducted so far show that psoriasis is a multifactorial polygenetic disease with reduced gene penetration. They also show that heredity is more significant than the "trigger" factor whose influence is limited to the exchange of phenotypes. Researches in USA, Canada and Europe identified four most important loci (psoriasis susceptibility - 1-4). At least one is in MHC (major histocompatibility complex) due to the connection between psoriasis and alleles of human leukocyte antigen (HLA). OBJECTIVE Our study included 117 patients and examined the indicators of genetic predisposition to psoriasis: frequency of psoriasis among relatives of psoriatic probands; frequency of psoriasis among relatives (I and II degree) of psoriatic patients; age of probands and other relatives at the onset of illness. Material and methods We have used a structured questionnaire for collection of data about existence of psoriasis in relatives of I and II degree of psoriatic probands and about the age of probands and relatives at the time of onset. Results and discussion Twenty six (21.85%) probands have at least one ill relative. The examined patients who have diseased relatives get ill much earlier than those who do not. Probands with two or more diseased relatives get ill much earlier than those who have just one diseased relative. Analysis of our sample shows a significant statistical difference regarding the onset of illness of diseased parents and their children. Children get ill earlier. CONCLUSIONS We have concluded that in our sample there is a hereditary component which is related to frequency and onset of psoriasis.

HLA-B27 and disease pathogenesis: new structural and functional insights

1999 ◽  
Vol 1 (16) ◽  
pp. 1-10 ◽  
Author(s):  
Paul Bowness ◽  
Nathan Zaccai ◽  
Lucy Bird ◽  
E. Yvonne Jones
Keyword(s):  
Cell Biology ◽  
Molecular Model ◽  
Human Leukocyte ◽  
Antigenic Peptides ◽  
Hla B27 ◽  
Leukocyte Antigen ◽  
Histocompatibility Complex ◽  
Arthritogenic Peptide ◽  
Mhc Antigen

The human leukocyte antigen class I allele HLA-B27 is a major histocompatibility complex (MHC) antigen that is strongly associated with the spondyloarthritic group of human rheumatic diseases, the most commmon of which is ankylosing spondylitis. Although the mechanism underlying this disease association remains unknown, numerous theories have been proposed. Much more is known of the natural role of HLA-B27 in binding and presenting antigenic peptides to T cells. The ‘arthritogenic peptide hypothesis’ suggests that the role of HLA-B27 in disease relates to its specificity for binding certain peptides. Recently, it has also been shown that HLA-B27 has an unusual cell biology and can adopt a novel homodimeric structure. In this review, a molecular model of the HLA-B27 homodimer is presented and the possible pathogenic significance of such a structure is discussed.

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