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1.
Methods Mol Biol ; 2552: 3-59, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36346584

RESUMO

IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org , the global reference in immunogenetics and immunoinformatics, was created in 1989 by Marie-Paule Lefranc (Université de Montpellier and CNRS) to manage the huge diversity of the antigen receptors, immunoglobulins (IG) or antibodies, and T cell receptors (TR) of the adaptive immune responses. The founding of IMGT® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT® standardized analysis of the IG, TR, and major histocompatibility (MH) genes and proteins bridges the gap between sequences and three-dimensional (3D) structures, for all jawed vertebrates from fish to humans. This is achieved through the IMGT Scientific chart rules, based on the IMGT-ONTOLOGY axioms, and primarily CLASSIFICATION (IMGT gene and allele nomenclature) and NUMEROTATION (IMGT unique numbering and IMGT Colliers de Perles). IMGT® comprises seven databases (IMGT/LIGM-DB for nucleotide sequences, IMGT/GENE-DB for genes and alleles, etc.), 17 tools (IMGT/V-QUEST, IMGT/JunctionAnalysis, IMGT/HighV-QUEST for NGS, etc.), and more than 20,000 Web resources. In this chapter, the focus is on the tools for amino acid sequences per domain (IMGT/DomainGapAlign and IMGT/Collier-de-Perles), and on the databases for receptors (IMGT/2Dstructure-DB and IMGT/3D-structure-DB) described per receptor, chain, and domain and, for 3D, with contact analysis, paratope, and epitope. The IMGT/mAb-DB is the query interface for monoclonal antibodies (mAb), fusion proteins for immune applications (FPIA), composite proteins for clinical applications (CPCA), and related proteins of interest (RPI) with links to IMGT® 2D and 3D databases and to the World Health Organization (WHO) International Nonproprietary Names (INN) program lists. The chapter includes the human IG allotypes and antibody engineered variants for effector properties used in the description of therapeutical mAb.


Assuntos
Imunogenética , Imunoglobulinas , Humanos , Animais , Imunogenética/métodos , Imunoglobulinas/genética , Imunoglobulinas/química , Anticorpos/genética , Biologia Computacional/métodos , Sequência de Aminoácidos , Receptores de Antígenos de Linfócitos T/genética
2.
Vox Sang ; 117(11): 1332-1344, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36121188

RESUMO

BACKGROUND AND OBJECTIVES: Under the ISBT, the Working Party (WP) for Red Cell Immunogenetics and Blood Group Terminology is charged with ratifying blood group systems, antigens and alleles. This report presents the outcomes from four WP business meetings, one located in Basel in 2019 and three held as virtual meetings during the COVID-19 pandemic in 2020 and 2021. MATERIALS AND METHODS: As in previous meetings, matters pertaining to blood group antigen nomenclature were discussed. New blood group systems and antigens were approved and named according to the serologic, genetic, biochemical and cell biological evidence presented. RESULTS: Seven new blood group systems, KANNO (defined numerically as ISBT 037), SID (038), CTL2 (039), PEL (040), MAM (041), EMM (042) and ABCC1 (043) were ratified. Two (039 and 043) were de novo discoveries, and the remainder comprised reported antigens where the causal genes were previously unknown. A further 15 blood group antigens were added to the existing blood group systems: MNS (002), RH (004), LU (005), DI (010), SC (013), GE (020), KN (022), JMH (026) and RHAG (030). CONCLUSION: The ISBT now recognizes 378 antigens, of which 345 are clustered within 43 blood group systems while 33 still have an unknown genetic basis. The ongoing discovery of new blood group systems and antigens underscores the diverse and complex biology of the red cell membrane. The WP continues to update the blood group antigen tables and the allele nomenclature tables. These can be found on the ISBT website (http://www.isbtweb.org/working-parties/red-cell-immunogenetics-and-blood-group-terminology/).


Assuntos
Antígenos de Grupos Sanguíneos , COVID-19 , Eritrócitos , Humanos , Antígenos de Grupos Sanguíneos/genética , Transfusão de Sangue , Imunogenética , Pandemias , Eritrócitos/imunologia
3.
Int J Immunogenet ; 49(5): 345-352, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36029282

RESUMO

Human neutrophil antigens possess significant clinical implications especially in the fields of transfusion and transplantation medicine. Efforts to estimate the prevalence of genetic variations underpinning the antigenic expression are emerging. However, there lacks a precise capture of the global frequency profiles. Our article emphasizes the potential utility of maintaining an organized online repository of evidence on neutrophil antigen-associated genetic variants from published literature and reports. This, in our opinion, is an emerging area and would significantly benefit from the awareness and understanding of population-level diversities.


Assuntos
Antígenos HLA , Neutrófilos , Frequência do Gene , Antígenos HLA/genética , Humanos , Imunogenética , Epidemiologia Molecular
4.
Methods Mol Biol ; 2511: 133-147, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35838957

RESUMO

SARS-CoV-2 causes generally mild symptoms, with approximately 10-20% of cases progressing to severe disease. The pathophysiologic mechanisms by which SARS-CoV-2 causes severe disease are largely unknown. Data have indicated the involvement of different immunogenetic markers such as HLA, T, and B cells, to be associated with disease outcome. This has led to interest in these genes as potential biomarkers of SARS-CoV-2 susceptibility and for predicting prognosis and response to vaccines and other therapeutic strategies. In this chapter, we discussed outline protocols for characterizing these potential biomarkers and methods for identifying SARS-CoV-2 biomarkers using the Luminex® 100/200 technology and next-generation sequencing.


Assuntos
COVID-19 , SARS-CoV-2 , Biomarcadores , COVID-19/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunogenética , SARS-CoV-2/genética
5.
Immunogenetics ; 74(5): 445-446, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35788884

Assuntos
Imunogenética
6.
Ann Hematol ; 101(7): 1567-1576, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35525883

RESUMO

Despite advances in the understanding of the pathophysiology of cytomegalovirus (CMV) infection, it remains as one of the most common infectious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study was to determine the genotype of cytokines and chemokines in donor and recipient and their association with CMV reactivation. Eighty-five patients receiving an allo-HSCT from an HLA-identical sibling donor were included in the study. Fifty genes were selected for their potential role in the pathogenesis of CMV infection. CMV DNAemia was evaluated until day 180 after allo-HSCT. CMV reactivation was observed in 51/85 (60%) patients. Of the 213 genetic variants selected, 11 polymorphisms in 7 different genes (CXCL12, IL12A, KIR3DL1, TGFB2, TNF, IL1RN, and CD48) were associated with development or protection from CMV reactivation. A predictive model using five of such polymorphisms (CXCL12 rs2839695, IL12A rs7615589, KIR3DL1 rs4554639, TGFB2 rs5781034 for the recipient and CD48 rs2295615 for the donor) together with the development of acute GVHD grade III/IV improved risk stratification of CMV reactivation. In conclusion, the data presented suggest that the screening of five polymorphisms in recipient and donor pre-transplantation could help to predict the individual risk of CMV infection development after HLA-identical allo-HSCT.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Citomegalovirus/genética , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunogenética , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos
7.
Immunogenetics ; 74(4): 367, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35622084

Assuntos
Imunogenética
8.
Sci Rep ; 12(1): 7235, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508592

RESUMO

Human leukocyte antigen (HLA) genes have been implicated in cancer risk and shared heritability of different types of cancer. In this immunogenetic epidemiological study we first computed a Cancer-HLA profile for 30 cancer types characterized by the correlation between the prevalence of each cancer and the population frequency of 127 HLA alleles, and then used multidimensional scaling to evaluate the possible clustering of those Cancer-HLA associations. The results indicated the presence of three clusters, broadly reflecting digestive-skin-cervical cancers, reproductive and endocrine systems cancers, and brain and androgen-associated cancers. The clustering of cancer types documented here is discussed in terms of mechanisms underlying shared Cancer-HLA associations.


Assuntos
Imunogenética , Neoplasias do Colo do Útero , Alelos , Análise por Conglomerados , Feminino , Frequência do Gene , Predisposição Genética para Doença , Antígenos HLA/genética , Humanos , Neoplasias do Colo do Útero/genética
9.
Curr Pharm Des ; 28(22): 1780-1797, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35598232

RESUMO

Coronavirus disease 2019 (COVID-19) continues to spread globally despite the discovery of vaccines. Many people die due to COVID-19 as a result of catastrophic consequences, such as acute respiratory distress syndrome, pulmonary embolism, and disseminated intravascular coagulation caused by a cytokine storm. Immunopathology and immunogenetic research may assist in diagnosing, predicting, and treating severe COVID-19 and the cytokine storm associated with COVID-19. This paper reviews the immunopathogenesis and immunogenetic variants that play a role in COVID-19. Although various immune-related genetic variants have been investigated in relation to severe COVID-19, the NOD-like receptor protein 3 (NLRP3) and interleukin 18 (IL-18) have not been assessed for their potential significance in the clinical outcome. Here, we a) summarize the current understanding of the immunogenetic etiology and pathophysiology of COVID-19 and the associated cytokine storm; and b) construct and analyze protein-protein interaction (PPI) networks (using enrichment and annotation analysis) based on the NLRP3 and IL18 variants and all genes, which were established in severe COVID-19. Our PPI network and enrichment analyses predict a) useful drug targets to prevent the onset of severe COVID-19, including key antiviral pathways such as Toll-Like-Receptor cascades, NOD-like receptor signaling, RIG-induction of interferon (IFN) α/ß, and interleukin (IL)-1, IL-6, IL-12, IL-18, and tumor necrosis factor signaling; and b) SARS-CoV-2 innate immune evasion and the participation of MYD88 and MAVS in the pathophysiology of severe COVID-19. The PPI network genetic variants may be used to predict more severe COVID-19 outcomes, thereby opening the door for targeted preventive treatments.


Assuntos
COVID-19 , Antivirais , Síndrome da Liberação de Citocina , Humanos , Imunogenética , Interleucina-18 , Proteína 3 que Contém Domínio de Pirina da Família NLR , SARS-CoV-2
10.
Methods Mol Biol ; 2453: 1-5, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35622317

RESUMO

Adaptive immune cells (i.e., lymphocytes of the B and T lineage) are equipped with unique antigen receptors, which collectively form a highly diverse repertoire. Within the lymphocytes, the antigen receptor diversity is created at the DNA level through recombination processes in the immunoglobulin (IG) and T cell receptor (TR) genes that encode these receptors. This gives rise to an enormous immune repertoire (a.k.a. the "immunome") that can be studied in health and disease, both in a scientific and clinical context. In fact, the inherent distinctiveness of the IG/TR rearrangements on a per cell basis allows their usage as unique DNA fingerprints, which enables precision medicine, or for that matter "precision immunology." The field of (fundamental and translational) research on IG/TR repertoire diversity is the topic of the Immunogenetics volume in the Methods in Molecular Biology series.


Assuntos
Imunogenética , Imunoglobulinas , Rearranjo Gênico , Imunogenética/métodos , Imunoglobulinas/genética , Receptores de Antígenos de Linfócitos T/genética
11.
Methods Mol Biol ; 2453: 133-152, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35622325

RESUMO

In the era of genomic medicine, targeted next generation sequencing strategies (NGS) are becoming increasingly adopted by clinical molecular diagnostic laboratories to identify genetic diagnostic and prognostic biomarkers in hemato-oncology. We describe the EuroClonality-NGS DNA Capture (EuroClonality-NDC) assay, which is designed to simultaneously detect B and T cell clonal rearrangements, translocations, copy number alterations, and sequence variants. The accompanying validated bioinformatics pipeline enables production of an integrated report. The combination of the laboratory protocol and bioinformatics pipeline in the EuroClonality-NDC minimizes the potential for human error, reduces economic costs compared to current molecular testing strategies, and should improve diagnostic outcomes.


Assuntos
Imunogenética , Receptores de Antígenos de Linfócitos T , Variações do Número de Cópias de DNA , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Imunoglobulinas/genética , Receptores de Antígenos de Linfócitos T/genética
12.
Methods Mol Biol ; 2453: 477-531, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35622340

RESUMO

The variable domains (V-DOMAIN) of the antigen receptors, immunoglobulins (IG) or antibodies and T cell receptors (TR), which specifically recognize the antigens show a huge diversity in their sequences. This diversity results from the complex mechanisms involved in the synthesis of these domains at the DNA level (rearrangements of the variable (V), diversity (D), and joining (J) genes; N-diversity; and, for the IG, somatic hypermutations). The recognition of V, D, and J as "genes" and their entry in databases mark the creation of IMGT by Marie-Paule Lefranc, and the origin of immunoinformatics in 1989. For 30 years, IMGT®, the international ImMunoGeneTics information system® http://www.imgt.org , has implemented databases and developed tools for IG and TR immunoinformatics, based on the IMGT Scientific chart rules and IMGT-ONTOLOGY concepts and axioms, and more particularly, the princeps ones: IMGT genes and alleles (CLASSIFICATION axiom) and the IMGT unique numbering and IMGT Collier de Perles (NUMEROTATION axiom). This chapter describes the online tools for the characterization and annotation of the expressed V-DOMAIN sequences: (a) IMGT/V-QUEST analyzes in detail IG and TR rearranged nucleotide sequences, (b) IMGT/HighV-QUEST is its high throughput version, which includes a module for the identification of IMGT clonotypes and generates immunoprofiles of expressed V, D, and J genes and alleles, (c) IMGT/StatClonotype performs the pairwise comparison of IMGT/HighV-QUEST immunoprofiles, (d) IMGT/DomainGapAlign analyzes amino acid sequences and is frequently used in antibody engineering and humanization, and (e) IMGT/Collier-de-Perles provides two-dimensional (2D) graphical representations of V-DOMAIN, bridging the gap between sequences and 3D structures. These IMGT® tools are widely used in repertoire analyses of the adaptive immune responses in normal and pathological situations and in the design of engineered IG and TR for therapeutic applications.


Assuntos
Biologia Computacional , Imunogenética , Sequência de Aminoácidos , Anticorpos/genética , Biologia Computacional/métodos , Imunogenética/métodos , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/genética
13.
Am J Hum Genet ; 109(6): 1105-1116, 2022 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-35550063

RESUMO

Glioma is a highly fatal cancer with prognostically significant molecular subtypes and few known risk factors. Multiple studies have implicated infections in glioma susceptibility, but evidence remains inconsistent. Genetic variants in the human leukocyte antigen (HLA) region modulate host response to infection and have been linked to glioma risk. In this study, we leveraged genetic predictors of antibody response to 12 viral antigens to investigate the relationship with glioma risk and survival. Genetic reactivity scores (GRSs) for each antigen were derived from genome-wide-significant (p < 5 × 10-8) variants associated with immunoglobulin G antibody response in the UK Biobank cohort. We conducted parallel analyses of glioma risk and survival for each GRS and HLA alleles imputed at two-field resolution by using data from 3,418 glioma-affected individuals subtyped by somatic mutations and 8,156 controls. Genetic reactivity scores to Epstein-Barr virus (EBV) ZEBRA and EBNA antigens and Merkel cell polyomavirus (MCV) VP1 antigen were associated with glioma risk and survival (Bonferroni-corrected p < 0.01). GRSZEBRA and GRSMCV were associated in opposite directions with risk of IDH wild-type gliomas (ORZEBRA = 0.91, p = 0.0099/ORMCV = 1.11, p = 0.0054). GRSEBNA was associated with both increased risk for IDH mutated gliomas (OR = 1.09, p = 0.040) and improved survival (HR = 0.86, p = 0.010). HLA-DQA1∗03:01 was significantly associated with decreased risk of glioma overall (OR = 0.85, p = 3.96 × 10-4) after multiple testing adjustment. This systematic investigation of the role of genetic determinants of viral antigen reactivity in glioma risk and survival provides insight into complex immunogenomic mechanisms of glioma pathogenesis. These results may inform applications of antiviral-based therapies in glioma treatment.


Assuntos
Infecções por Vírus Epstein-Barr , Glioma , Esclerose Múltipla , Antígenos Virais , Infecções por Vírus Epstein-Barr/complicações , Glioma/complicações , Glioma/genética , Herpesvirus Humano 4/genética , Humanos , Imunogenética , Esclerose Múltipla/genética
15.
J Gastroenterol Hepatol ; 37(6): 973-982, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35384041

RESUMO

BACKGROUND AND AIM: Humans with inborn errors of immunity (IEI), or primary immunodeficiencies, may be associated with a potential risk factor for early-onset gastrointestinal (GI) cancer. METHODS: We systematically reviewed all cases with clinical diagnoses of both an IEI and a GI cancer in three databases (MEDLINE, SCOPUS, and EMBASE). In total, 76 publications satisfying our inclusion criteria were identified, and data for 149 cases were analyzed. We also searched our institutional cancer registry for such cases. RESULTS: We identified 149 patients with both an IEI and a GI cancer, 95 presented gastric cancer, 13 small bowel cancer, 35 colorectal cancer, and 6 had an unspecified cancer or cancer at another site. Gastric and colon adenocarcinomas were the most common. For both gastric and colorectal cancers, age at onset was significantly earlier in patients with IEIs than in the general population, based on the SEER database. Common variable immunodeficiency (CVID) was the most common IEI associated with gastrointestinal cancer. About 12% of patients had molecular genetic diagnoses, the three most frequently implicated genes being ATM, CARMIL2, and CTLA4. Impaired humoral immunity and Epstein-Barr virus (EBV) infection were frequently reported as factors potentially underlying early-onset GI cancers in patients with IEIs. We identified one patient with CVID and early-onset gastric adenocarcinoma, recurrent diarrhea, and gastrointestinal CMV infection from a retrospective survey. CONCLUSION: Patients with IEIs should be considered at risk of early-onset GI cancers and should therefore undergo cancer screening at an earlier age.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Gastrointestinais , Neoplasias Gástricas , Infecções por Vírus Epstein-Barr/complicações , Neoplasias Gastrointestinais/epidemiologia , Herpesvirus Humano 4 , Humanos , Imunogenética , Estudos Retrospectivos , Neoplasias Gástricas/epidemiologia
16.
J Parkinsons Dis ; 12(s1): S13-S27, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35367971

RESUMO

Parkinson's disease (PD) is increasingly recognised as a systemic disorder in which inflammation might play a causative role rather than being a consequence or an epiphenomenon of the neurodegenerative process. Although growing genetic evidence links the central and peripheral immune system with both monogenic and sporadic PD, our understanding on how the immune system contributes to PD pathogenesis remains a daunting challenge. In this review, we discuss recent literature aimed at exploring the role of known genes and susceptibility loci to PD pathogenesis through immune system related mechanisms. Furthermore, we outline shared genetic etiologies and interrelations between PD and autoimmune diseases and underlining challenges and limitations faced in the translation of relevant allelic and regulatory risk loci to immune-pathological mechanisms. Lastly, with the field of immunogenetics expanding rapidly, we place these insights into a future context highlighting the prospect of immune modulation as a promising disease-modifying strategy.


Assuntos
Doença de Parkinson , Causalidade , Humanos , Sistema Imunitário , Imunogenética , Inflamação , Doença de Parkinson/genética
17.
Probl Endokrinol (Mosk) ; 68(2): 9-15, 2022 02 18.
Artigo em Russo | MEDLINE | ID: mdl-35488752

RESUMO

Primary hyperaldosteronism (PHA) is the most common form of endocrine hypertension. Until recently, the reason for the development of this condition was believed to be the presence of genetic mutations, however, many studies declare that the disease can be polyetiologic, be the result of genetic mutations and autoimmune triggers or cell clusters of aldosterone-producing cells diffusely located in the adrenal gland at the zona glonerulosa, zona fasculata, zona reticularis, as well as directly under the adrenal capsule. Recently, the actions of autoantibodies to type 1 angiotensin II receptors have been described in patients with renal transplant rejection, with preeclampsia, and with primary hyperaldosteronism. The diagnostic role of antibodies in both forms of PHA (aldosterone-producing adenoma and bilateral hyperaldosteronism) requires clarification. Diagnosis and confirmation of the focus of aldosterone hypersecretion is a multi-stage procedure that requires a long time and economic costs. The relevance of timely diagnosis of primary hyperaldosteronism is to reduce medical and social losses. This work summarizes the knowledge about genetic mutations and presents all the original studies devoted to autoantibodies in PHA, as well as discusses the diagnostic capabilities and limitations of the available methods of primary and differential diagnosis of the disease and the prospects for therapy.


Assuntos
Aldosterona , Hiperaldosteronismo , Glândulas Suprarrenais/metabolismo , Aldosterona/metabolismo , Autoanticorpos/genética , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/genética , Imunogenética
18.
Microbiome ; 10(1): 41, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35256003

RESUMO

BACKGROUND: The gut microbiome (GM) can influence many biological processes in the host, impacting its health and survival, but the GM can also be influenced by the host's traits. In vertebrates, Major Histocompatibility Complex (MHC) genes play a pivotal role in combatting pathogens and are thought to shape the host's GM. Despite this-and the documented importance of both GM and MHC variation to individual fitness-few studies have investigated the association between the GM and MHC in the wild. RESULTS: We characterised MHC class I (MHC-I), MHC class II (MHC-II) and GM variation in individuals within a natural population of the Seychelles warbler (Acrocephalus sechellensis). We determined how the diversity and composition of the GM varied with MHC characteristics, in addition to environmental factors and other host traits. Our results show that the presence of specific MHC alleles, but not MHC diversity, influences both the diversity and composition of the GM in this population. MHC-I alleles, rather than MHC-II alleles, had the greatest impact on the GM. GM diversity was negatively associated with the presence of three MHC-I alleles (Ase-ua3, Ase-ua4, Ase-ua5), and one MHC-II allele (Ase-dab4), while changes in GM composition were associated with the presence of four different MHC-I alleles (Ase-ua1, Ase-ua7, Ase-ua10, Ase-ua11). There were no associations between GM diversity and TLR3 genotype, but GM diversity was positively correlated with genome-wide heterozygosity and varied with host age and field period. CONCLUSIONS: These results suggest that components of the host's immune system play a role in shaping the GM of wild animals. Host genotype-specifically MHC-I and to a lesser degree MHC-II variation-can modulate the GM, although whether this occurs directly, or indirectly through effects on host health, is unclear. Importantly, if immune genes can regulate host health through modulation of the microbiome, then it is plausible that the microbiome could also influence selection on immune genes. As such, host-microbiome coevolution may play a role in maintaining functional immunogenetic variation within natural vertebrate populations. Video abstract.


Assuntos
Microbioma Gastrointestinal , Seleção Genética , Alelos , Animais , Microbioma Gastrointestinal/genética , Variação Genética/genética , Imunogenética , Vertebrados/genética
19.
Adv Exp Med Biol ; 1367: 105-117, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35286693

RESUMO

Psoriasis vulgaris is a chronic immune-mediated dermatological condition, resulting from an interaction between environmental triggers and genetic susceptibilities. Alteration in the production of the inflammatory mediators plays a pivotal part in the pathogenesis of the disease. Genes encoding the mediators of these inflammatory pathways can dictate susceptibility to psoriasis. These genes have a wide range of functions that involve innate immunity (IFIH1, TRAF3IP2, CARD14, c-REL, DDX58), antigen presentation (HLA-Cw6), T-cells development, maturation, and polarization (RUNX1, RUNX3, STAT3), cytokine signaling (IL12Bp40, IL23Ap19, IL23R, JAK2), and immune regulators (TNIP1, TNFAIP3, IL36RN, SOCS1, ZC3H12C, NFKBIA). The risk alleles of these genes can contribute to the overall state of susceptibility to psoriasis by lowering the threshold of the innate immune response that can eventually provoke the pathogenic adaptive immune responses capable of inducing psoriasis. The investigations on genetic associations of psoriasis may allow the discovery of new diseases modifying targets and possibly open a path for the advancement of personalized medicine. They also allow us to discover new aspects of human skin biology.


Assuntos
Proteínas Adaptadoras de Sinalização CARD , Imunogenética , Psoríase , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Predisposição Genética para Doença , Guanilato Ciclase/genética , Humanos , Imunidade Inata/genética , Interleucinas/metabolismo , Proteínas de Membrana/metabolismo , Psoríase/genética , Psoríase/metabolismo , Pele/metabolismo
20.
Adv Exp Med Biol ; 1367: 1-17, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35286690

RESUMO

Genetics plays a major role in shaping the immune responses in both physiological and pathological states such as psoriasis, alopecia areata, and other immune-mediated dermatological conditions. The genes encoding the elements of the immune system and its regulators are among the most polymorphous loci in the genome. Subtle variations in these genes can thus alter the balanced defensive responses of the immune system and make an individual liable to diseases and environmental triggers. Immunogenetics deals with finding the precise set of liability genes involved in the pathogenesis of specific complex diseases. In this chapter, we will briefly discuss the basic principles of genetic polymorphisms, the methods used in scanning these polymorphisms, and the strategies employed to find the role of these polymorphisms in complex diseases.


Assuntos
Alopecia em Áreas , Psoríase , Alopecia em Áreas/genética , Humanos , Imunogenética , Polimorfismo Genético , Psoríase/patologia
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