RESUMO
The human leukocyte antigen (HLA) system is one of the most crucial host factors influencing disease progression in bacterial and viral infections. This review provides the basic concepts of the structure and function of HLA molecules in humans. Here, we highlight the main findings on the associations between HLA class I and class II alleles and susceptibility to important infectious diseases such as tuberculosis, leprosy, melioidosis, Staphylococcus aureus infection, human immunodeficiency virus infection, coronavirus disease 2019, hepatitis B, and hepatitis C in populations worldwide. Finally, we discuss challenges in HLA typing to predict disease outcomes in clinical implementation. Evaluation of the impact of HLA variants on the outcome of bacterial and viral infections would improve the understanding of pathogenesis and identify those at risk from infectious diseases in distinct populations and may improve the individual treatment.
Assuntos
COVID-19 , Alelos , COVID-19/genética , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe II , HumanosRESUMO
In Human, Major Histocompatibility Complex known as Human Leukocyte Antigen (HLA). The HLA grouped into three subclasses regions: the class I region, the class II region, and the class III region. There are thousands of polymorphic HLAs, many of them are proven to have correlations with diseases. Indonesia consists of diverse ethnicity people and populations. It carries a unique genetic diversity between one and another geographical positions. This paper aims to extract Indonesians HLA allele data, mapping the data, and correlating them with global diseases. From the study, it is found that global diseases, like Crohn's disease, rheumatoid arthritis, Graves' disease, gelatin allergy, T1D, HIV, systemic lupus erythematosus, juvenile chronic arthritis, and Mycobacterial disease (tuberculosis and leprosy) suspected associated with the Indonesian HLA profiles.
Assuntos
Doença/genética , Predisposição Genética para Doença/genética , Antígenos HLA/genética , Alelos , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença/epidemiologia , Variação Genética , Humanos , Indonésia/epidemiologia , PrevalênciaRESUMO
BACKGROUND: Killer-cell immunoglobulin-like receptors (KIRs) are a group of regulatory molecules able to activate or inhibit natural killer cells upon interaction with human leukocyte antigen (HLA) class I molecules. Combinations of KIR and HLA may contribute to the occurrence of different immunological and clinical responses to infectious diseases. Leprosy is a chronic neglected disease, both disabling and disfiguring, caused mainly by Mycobacterium leprae. In this case-control study, we examined the influence of KIRs and HLA ligands on the development of multibacillary leprosy. METHODOLOGY/PRINCIPAL FINDINGS: Genotyping of KIR and HLA genes was performed in 264 multibacillary leprosy patients and 518 healthy unrelated controls (238 healthy household contacts and 280 healthy subjects). These are unprecedented results in which KIR2DL2/KIR2DL2/C1/C2 and KIR2DL3/2DL3/C1/C1 indicated a risk for developing lepromatous and borderline leprosy, respectively. Concerning to 3DL2/A3/A11+, our study demonstrated that independent of control group (contacts or healthy subjects), this KIR receptor and its ligand act as a risk factor for the borderline clinical form. CONCLUSIONS/SIGNIFICANCE: Our finding suggests that synergetic associations of activating and inhibitory KIR genes may alter the balance between these receptors and thus interfere in the progression of multibacillary leprosy.
Assuntos
Predisposição Genética para Doença , Antígenos HLA/genética , Hanseníase Multibacilar/genética , Receptores KIR/genética , Adulto , Idoso , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Hanseníase Multibacilar/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças NegligenciadasRESUMO
Despite the use of multidrug therapy, leprosy remains endemic in some countries. The association of several human leucocyte antigen (HLA) alleles and gene polymorphisms with leprosy has been demonstrated in many populations, but the major immune contributors associated to the spectrum of leprosy have not been defined yet. In this study, genotyping of HLA-A, -B, -DR, and -DQ alleles was performed in leprosy patients (n = 113) and control subjects (n = 117) from the region with the highest incidence for the disease in México. The odds of developing leprosy and lepromatous subtype were 2.12- and 2.74-fold higher in carriers of HLA-A*28, and 2.48- and 4.14-fold higher for leprosy and dimorphic subtype in carriers of DQB1*06. Interestingly, DQB1*07 was overrepresented in healthy individuals, compared to patients with leprosy (OR = 0.08) and the lepromatous subtype (OR = 0.06). These results suggest that HLA-A*28 is a marker for predisposition to leprosy and the lepromatous subtype and DQB1*06 to leprosy and the dimorphic subtype, while DQB1*07 might be a resistance marker in this Mestizo population.
Assuntos
Antígenos HLA/genética , Indígenas Norte-Americanos/genética , Hanseníase/genética , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Masculino , México , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
Many genes including HLA, KIR, and MICA genes, as well as polymorphisms in cytokines have been investigated for their role in infectious disease. HLA alleles may influence not only susceptibility or resistance to leprosy, but also the course of the disease. Some combinations of HLA and KIR may result in negative as well as positive interactions between NK cells and infected host cells with M. leprae, resulting in activation or inhibition of NK cells and, consequently, in death of bacillus. In addition, studies have demonstrated the influence of MICA genes in the pathogenesis of leprosy. Specifically, they may play a role in the interaction between NK cells and infected cells. Finally, pro- and anti-inflammatory cytokines have been influencing the clinical course of leprosy. Data from a wide variety of sources support the existence of genetic factors influencing the leprosy pathogenesis. These sources include twin studies, segregation analyses, family-based linkage and association studies, candidate gene association studies, and, most recently, genome-wide association studies (GWAS). The purpose of this brief review was to highlight the importance of some immune response genes and their correlation with the clinical forms of leprosy, as well as their implications for disease resistance and susceptibility.
Assuntos
Citocinas/genética , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Hanseníase/genética , Receptores KIR/genética , Alelos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Células Matadoras Naturais/metabolismo , Hanseníase/imunologia , Hanseníase/patologia , Receptores KIR/imunologiaRESUMO
Leprosy is a chronic infectious disease that affects 600,000 new individuals worldwide every year. This article summarizes some of the advances achieved over the past decades towards the description of the exact number, location and nature of the genetic variants responsible for the well established genetic component controlling leprosy susceptibility in humans.
Assuntos
Predisposição Genética para Doença , Antígenos HLA/genética , Hanseníase/genética , Genoma Humano , Humanos , Hanseníase/imunologia , Polimorfismo GenéticoAssuntos
Predisposição Genética para Doença , Hanseníase/genética , Hanseníase/imunologia , Mycobacterium leprae/imunologia , Polimorfismo Genético , Membro 3 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Abatacepte , Proteínas de Transporte de Cátions/genética , Proteína de Ligação ao Complemento C4b , Antígenos HLA/genética , Antígenos de Histocompatibilidade/genética , Humanos , Imunoconjugados/genética , Interleucina-10/genética , Hanseníase/microbiologia , Glicoproteínas de Membrana/genética , Proteínas dos Microfilamentos , Chaperonas Moleculares , Proteínas/genética , Receptores de Superfície Celular/genética , Receptores Toll-Like , Fator de Necrose Tumoral alfa/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
Each year an estimated 600000 new leprosy cases are diagnosed worldwide. The spectrum of the disease varies widely from limited tuberculoid forms to extensive lepromatous forms. A measure of the risk to develop lepromatous forms of leprosy is provided by the extent of skin reactivity to lepromin (Mitsuda reaction). To address a postulated oligogenic control of leprosy pathogenesis, we investigated in the present study linkage of leprosy susceptibility, leprosy clinical subtypes, and extent of the Mitsuda reaction to six chromosomal regions carrying known or suspected leprosy susceptibility loci. The only significant result obtained was linkage of leprosy clinical subtype to the HLA/TNF region on human chromosome 6p21 (P(corrected)=0.00126). In addition, we established that within the same family different HLA/TNF haplotypes segregate into patients with different leprosy subtypes directly demonstrating the importance of this genome region for the control of clinical leprosy presentation.
Assuntos
Ligação Genética/genética , Antígenos HLA/genética , Hanseníase/genética , Fator de Necrose Tumoral alfa/genética , Cromossomos Humanos Par 6/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Hanseníase/classificação , Masculino , Linhagem , FenótipoRESUMO
Each year an estimated 600000 new leprosy cases are diagnosed worldwide. The spectrum of the disease varies widely from limited tuberculoid forms to extensive lepromatous forms. A measure of the risk to develop lepromatous forms of leprosy is provided by the extent of skin reactivity to lepromin (Mitsuda reaction). To address a postulated oligogenic control of leprosy pathogenesis, we investigated in the present study linkage of leprosy susceptibility, leprosy clinical subtypes, and extent of the Mitsuda reaction to six chromosomal regions carrying known or suspected leprosy susceptibility loci. The only significant result obtained was linkage of leprosy clinical subtype to the HLA/TNF region on human chromosome 6p21 (P(corrected)=0.00126). In addition, we established that within the same family different HLA/TNF haplotypes segregate into patients with different leprosy subtypes directly demonstrating the importance of this genome region for the control of clinical leprosy presentation.
Assuntos
Masculino , Feminino , Humanos , Antígenos HLA/genética , /genética , Fator de Necrose Tumoral alfa/genética , Genótipo , Hanseníase/classificação , Hanseníase/genética , Ligação Genética/genética , Predisposição Genética para Doença , Fenótipo , LinhagemRESUMO
BACKGROUND: The epidemiology of leprosy in rural Egypt is unknown. This prospective household survey was conducted in a high-prevalence Egyptian village in order to explore the epidemiologic characteristics of the disease and to determine the possible socioeconomic and HLA genotype risk factors. METHODS: The subjects of the study were the residents of Kafr-Tambul village in the Dakahlia governorate, Egypt. There were 10,503 inhabitants of the village, of whom 9643 (91.8%) had a complete visual skin examination, and suspected leprosy patients were subjected to histopathological examination and slit skin smears. Each household was interviewed to record personal data on family members, family size, education, occupation, crowding index at sleep, social score and source of water supply. Human leukocyte antigen (HLA) class II genotypes were analyzed in all leprosy patients and in a number of both household (N = 124) and non-household (N = 30) contacts. RESULTS: The overall prevalence of clinical leprosy in the village studied was 24.9/10,000 (95%CI = 16.3-37.6). Individuals above the age of 40 years were 4 times more likely to develop leprosy (OR = 4, P= 0.01). The degree of education, crowding index at sleep, social score and source of water supply were found to be unlikely to increase the risk of leprosy (P > 0.05). The frequencies of HLA-DR2 and -DQ1 were significantly associated with leprosy (OR = 3.33 and 5.4; CI = 0.95-12.07 and 1.08-30.19, respectively, all P < 0.05). CONCLUSIONS: Our study provides the first picture of the epidemiology of leprosy in a high-prevalence village in rural Egypt. Leprosy detection campaigns should be initiated and directed towards high-prevalence villages. Provision of leprosy control activities in rural health units is necessary in order to detect new cases. The risk for leprosy is associated with HLA-DR2 and -DQ1 markers, and these markers appear to increase personal susceptibility to leprosy in this village.