Aspectos genéticos da esclerose múltipla: II. sistema HLA

Rezende, Patrícia Almeida de; Arruda, Walter Oleschko

doi:10.1590/s0004-282x1996000300013

Cited by 3 publications

(3 citation statements)

References 36 publications

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“…Multiple sclerosis, an auto-immune disease that has been controversially reported as being possibly triggered by viral infections [50], is positively associated with HLA-A*02, C*08, DRB1*15, DQA1*01, and DQB1*06 [51], [52], whereas HLA-B*44 is reported to be protective [53]. The HSV-induced Behcet's syndrome [54] is more common in individuals expressing HLA-B*51 [55], [56].…”

Section: Discussionmentioning

confidence: 99%

Association between HLA Class I and Class II Alleles and the Outcome of West Nile Virus Infection: An Exploratory Study

et al. 2011

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BackgroundWest Nile virus (WNV) infection is asymptomatic in most individuals, with a minority developing symptoms ranging from WNV fever to serious neuroinvasive disease. This study investigated the impact of host HLA on the outcome of WNV disease.MethodsA cohort of 210 non-Hispanic mostly white WNV+ subjects from Canada and the U.S. were typed for HLA-A, B, C, DP, DQ, and DR. The study subjects were divided into three WNV infection outcome groups: asymptomatic (AS), symptomatic (S), and neuroinvasive disease (ND). Allele frequency distribution was compared pair-wise between the AS, S, and ND groups using χ2 and Fisher's exact tests and P values were corrected for multiple comparisons (Pc). Allele frequencies were compared between the groups and the North American population (NA) used as a control group. Logistic regression analysis was used to evaluate the potential synergistic effect of age and HLA allele phenotype on disease outcome.ResultsThe alleles HLA-A*68, C*08 and DQB*05 were more frequently associated with severe outcomes (ND vs. AS, P A*68 = 0.013/Pc = 0.26, P C*08 = 0.0075/Pc = 0.064, and P DQB1*05 = 0.029/Pc = 0.68), However the apparent DQB1*05 association was driven by age. The alleles HLA-B*40 and C*03 were more frequently associated with asymptomatic outcome (AS vs. S, P B*40 = 0.021/Pc = 0.58 and AS vs. ND P C*03 = 0.039/Pc = 0.64) and their frequencies were lower within WNV+ subjects with neuroinvasive disease than within the North American population (NA vs. S, P B*40 = 0.029 and NA vs. ND, P C*03 = 0.032).ConclusionsHost HLA may be associated with the outcome of WNV disease; HLA-A*68 and C*08 might function as “susceptible” alleles, whereas HLA-B*40 and C*03 might function as “protective” alleles.

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Section: Discussionmentioning

confidence: 99%

Association between HLA Class I and Class II Alleles and the Outcome of West Nile Virus Infection: An Exploratory Study

et al. 2011

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“…Therefore, the importance of the blood-brain barrier in the early pathogenesis of inflammation of the central nervous system is revealed, an aspect further corroborated by the fact that its endothelial cells induce the differentiation of CD209 dendritic cells and, subsequently, secrete interleukin-12p70 (IL-12p70), TGFβ and IL-6, thus providing the differentiation of virgin cells into effector cells of Th1 or Th17 profile (IFERGAN et al, 2008). It is assumed that an autoimmune response that causes overexpression of inflammation mediators in sick individuals, such as interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-3 (IL-3), IFN-γ, TNF-α and tumor necrosis factor-β (TNF-ß), induces the expression of specific molecules in the membrane of central nervous system cells and activates the phagocytic function of microglia cells, as we will see below (REZENDE;ARRUDA, 1998). It is also worth noting that in addition to CD4+ T cells, CD8+ T cells predominate and proliferate in the central nervous system, exhibiting a relevant role in myelin and oligodendrocyte injury, due to the interaction with MHC class I present in oligodendrocytes, neural bodies and axons (VIEGAS, 2009).…”

Section: Introductionmentioning

confidence: 99%

Multiple sclerosis and experimental autoimmune encephalomyelitis: A review

Cachuba,

Scherrer,

Ramos

et al. 2023

Uniting Knowledge Integrated Scientific Research for Global Development

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Multiple sclerosis is a chronic inflammatory autoimmune disease of the central nervous system, characterized by mononuclear cell infiltration, axon demyelination and gliosis in the myelin sheath, with formation of multiple plaques. It affects individuals aged between 25 and 50 years old, female and residents of higher latitudes. The etiology of multiple sclerosis is multifactorial and not fully understood; however, the influence of genetic predisposition and environmental factors on immune dysregulation is recognized. The pathophysiology of the disease is mediated by self-reactive T lymphocytes that respond to autoantigens from the central nervous system. The emergence of multifocal regions of demyelination, axonal loss, loss of oligodendrocytes and astroglial scarring result in impaired neurological function, leading to neurodegeneration. Although there is still no cure for multiple sclerosis, scientific research has provided great advances in therapeutic strategies. Currently there are approaches to attenuate specific signs and symptoms, drugs to control disease relapses and treatments designed to modify or delay the course of multiple sclerosis. Although these drugs show promising effects, they are ineffective in curing the patient. In addition, they present a fundamental problem, which is the non-selective action on the cells of the immune system, which triggers serious side effects. Considering the limitations of studies in humans due to the difficulty of accessing the affected tissues, the use of experimental models that simulate the singularities of multiple sclerosis is a key element for the study of the pathogenesis of inflammation and therapeutic alternatives. Experimental autoimmune encephalomyelitis, an animal model that presents several similarities with pathophysiological, histological and clinical aspects of multiple sclerosis, is the most used model for these studies. Therefore, in this chapter, the aim was to review the historical context, definition, etiology, pathophysiology, clinical manifestations, diagnosis and treatment of multiple sclerosis and, at the same time, address aspects of the timeline, induction, the evolutionary course and the immunopathogenesis of the most studied model for the investigation of the nuances of multiple sclerosis, correlating the similarities and differences between both.

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“…Em sua maioria, os genes do complexo HLA são altamente polimórficos e as variantes de seus alelos estão implicadas na susceptibilidade e/ou proteção a várias doenças autoimunes 5 . Tem sido descrita forte associação dos alelos DQB1*0602, DQA1*0102 e DRB1*1501 que compõem o haplótipo DR2 no desenvolvimento da EM na população caucasiana 6,7 . Contudo, o alelo DQB1*0602 parece conferir susceptibilidade à doença, mesmo na ausência da expressão dos alelos DQA1*0102, DRB1*1501 8 .…”

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Determinação de autoanticorpos para antígenos da mielina no soro de pacientes HLA - DQB1*0602 com esclerose múltipla

Carvalho

Sant'anna

Santos

et al. 2003

Arq. Neuro-Psiquiatr.

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RESUMO -Esclerose múltipla (EM) é doença inflamatória desmielinizante do sistema nervoso central (SNC) de natureza autoimune, mediada por linfócitos Th1. A produção de autoanticorpos séricos para proteína básica da mielina (MBP), proteolipídeo PLP e sequência da glicoproteína de oligodendrócito MOG 92-106, foi determinada em 54 indivíduos saudáveis e 26 pacientes com EM expressando ou não o alelo de suscetibilidade HLA-DQB1*0602. Independentemente da expressão do alelo DQB1*0602, todos os pacientes apresentaram produção marcante (p< 0,0001) de autoanticorpos isotipo IgG para MBP e MOG 92-106, e do isotipo IgA para PLP e MOG 92-106. Os resultados sugerem que outros alelos HLA da classe II exerçam influência na suscetibilidade à EM e no reconhecimento imunológico dos antígenos encefalitogênicos, determinando o padrão de resposta autoimune e contribuindo na manutenção e/ou controle da inflamação no SNC.PALAVRAS-CHAVE: esclerose múltipla, desmielinização, autoimunidade, antígenos da mielina, HLA DQB1*0602. Determination of autoantibody for myelin antigens in the serum of patients HLA -DQB1*0602 with multiple sclerosisABSTRACT -Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system (CNS) mediated by autoimmune Th1 lymphocytes. We determined the serum levels of autoantibodies for myelin basic protein (MBP), proteolipid (PLP) and myelin oligodendrocyte glycoprotein sequence MOG 92-106 in a group of 54 healthy individuals and 26 MS patients expressing or not HLA DQB1*0602. Regardless expression of the susceptibility alelle DQB1*0602, MS patients presented marked (p<0.0001) IgG antibody production for MBP and MOG92-106. Yet, significant (p<0.0001) IgA antibody levels were mainly observed for PLP and MOG antigens. Our results suggest that other HLA class II alleles may be conferring susceptibility to MS in this population and influencing the pattern of immune recognition of encephalitogen antigens. Furthermore, distinct IgG and/or IgA autoantibody production may be contributing to the control or maintenance of the CNS inflammatory reaction.KEY WORDS: multiple sclerosis, demyelination, myelin antigens, autoimmunity, HLA, DQB1*0602.Esclerose múltipla (EM) é doença crônica inflamatória e desmielinizante do sistema nervoso central (SNC) de natureza autoimune, que apresenta intenso infiltrado perivenular de células mononucleares, perda de oligodendrócitos e lesão axonal [1][2][3][4] . Estudos epidemiológicos mostram distribuição heterogênea da doença pelo mundo e incidência em 0,1% da população nos países de clima temperado 2 . Nos países de clima tropical como o Brasil, a doença era considerada rara, porém dados recentes 3 relatam incidên-cia elevada da EM em indivíduos brancos e também nos de etnia negra (afro-brasileiros). EM é considerada doença de etiologia multifatorial, em que a existência de predisposição genética aliada a fatores externos seria determinante no desencadeamento dos eventos imunológicos relacionados com o processo inflamatório e desmielinizante no SNC ...

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Aspectos genéticos da esclerose múltipla: II. sistema HLA

Cited by 3 publications

References 36 publications

Association between HLA Class I and Class II Alleles and the Outcome of West Nile Virus Infection: An Exploratory Study

Association between HLA Class I and Class II Alleles and the Outcome of West Nile Virus Infection: An Exploratory Study

Multiple sclerosis and experimental autoimmune encephalomyelitis: A review

Determinação de autoanticorpos para antígenos da mielina no soro de pacientes HLA - DQB1*0602 com esclerose múltipla

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