The search for host determinants of susceptibility to rheumatic fever: the missing link. T. Duckett Jones Memorial Lecture.

Ayoub, Elía M.

doi:10.1161/01.cir.69.1.197

Cited by 33 publications

(16 citation statements)

References 15 publications

(2 reference statements)

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“…Numerous epidemiological studies indicating a high familial incidence suggest that hereditary factors may determine susceptibility to rheumatic fever (1)(2)(3). Early but unconfirmed studies suggested that susceptibility to rheumatic fever followed a simple autosomal recessive pattern of inheritance (4)(5)(6), or paralleled the inheritance of ABO blood group or ABO secretor status (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Association of class II human histocompatibility leukocyte antigens with rheumatic fever.

Ayoub¹,

Barrett²,

Maclaren³

et al. 1986

J. Clin. Invest.

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171

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The association of class I and II HLA antigens with rheumatic fever and its manifestations was examined in 72 patients, including 48 blacks and 24 Caucasians. No significant association was found between class I antigens and rheumatic fever. In contrast, HLA-DR2 and HLA-DR4 phenotypes were encountered in a significantly higher frequency in black and Caucasian patients with rheumatic fever, respectively, compared with the control populations (P < 0.005). The most significant association (P < 0.005) of these DR antigens with a major manifestation of rheumatic fever was found for mitral insufficiency. In addition, a significant association was encountered between persistent elevation of antibody to the group A streptococcal carbohydrate and HLA-DR4 in Caucasian patients (P < 0.04) or HLA-DR2 in the black patients (P < 0.001). The frequency of HLA-DR2/ 4 heterozygotes among patients with rheumatic fever did not differ significantly from controls. These findings support the concept of a genetically determined susceptibility to rheumatic fever and, particularly, to rheumatic heart disease. The association of the clinical manifestations of rheumatic fever and the immune hyperresponsiveness to a streptococcal antigen could be ascribed to a disease-associated immune-response gene which is in linkage disequilibrium with the DR2 and DR4 alleles of HLA-DR locus on chromosome six.

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Section: Introductionmentioning

confidence: 99%

Association of class II human histocompatibility leukocyte antigens with rheumatic fever.

Ayoub¹,

Barrett²,

Maclaren³

et al. 1986

J. Clin. Invest.

Self Cite

171

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“…O fato de somente um pequeno número de indivíduos expostos a estes microorganismos desenvolverem a FR ou a DCR aponta para a existência de mecanismos naturais de resistência à doença em indivíduos com resposta imunológica eficiente (1,3) . Paralelamente, a diversidade nas manifestações clínicas sugere o envolvimento de vários fatores na susceptibilidade da doença, tais como fatores genéticos, sociais e econômicos, além daqueles relacionados com a virulência do estreptococo.…”

Section: Discussionunclassified

“…(1) . Vários estudos apontam a influência genética na susceptibilidade da FR e da DCR (1)(2)(3) . Além da influência familiar (2)(3)(4) , associações significantes têm sido encontradas em diferentes populações, especialmente com antígenos da classe II do complexo principal de histocompatibilidade (MHC) (5)(6)(7) .…”

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“…Vários estudos apontam a influência genética na susceptibilidade da FR e da DCR (1)(2)(3) . Além da influência familiar (2)(3)(4) , associações significantes têm sido encontradas em diferentes populações, especialmente com antígenos da classe II do complexo principal de histocompatibilidade (MHC) (5)(6)(7) . Vários estudos demonstram significante associação entre diferentes alótipos do complemento e doenças autoimunes e infecciosas, tais como artrite reumatóide, esclerose múl-tipla, lúpus eritematoso sistêmico, doença de Chagas e hanseníase (8)(9)(10)(11)(12) .…”

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Associação do alótipo raro C4A6 do sistema complemento com a doença cardíaca reumática

Messias-Reason¹,

Cavalcanti²,

Radominski³

2004

Rev. Bras. Reumatol.

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RESUMOObjetivo: determinar se os alótipos do Fator B (BF), C2 e C4 (C4A e C4B) do sistema complemento poderiam ser marcadores para a doença cardíaca reumática (DCR) na população brasileira. Métodos: foram estudados 49 pacientes com DCR crônica. Os controles incluíram 65 indivíduos saudáveis, não aparentados, pareados com a amostra dos pacientes de acordo com o sexo, idade e grupo racial. Os alótipos de BF, C2, C4A e C4B foram determinados por técnicas-padrão, incluindo Western blot para a determinação das variantes de C2 e C4, utilizando-se anticorpos monoclonais e policlonais. Resultados: este estudo demonstrou um significante aumento do alelo raro C4A*6 (p=0,003 RR=11,85) e diminuição de C4A*3 nos pacientes, quando comparados com os controles. Além disso, alelos nulos de C4 e raros de C4 e BF foram observados com maior freqüência nos pacientes. Conclusões: considerando-se que foram avaliados somente pacientes com DCR, mais estudos serão necessários para que se possa esclarecer se o alelo C4A6 pode ser um marcador da forma cardíaca ou da própria doença.

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“…In the Brazilian population, the HLA-DR7 and DR53 alleles were found to be in strong association with RF/RHD among mulatto Brazilian patients [5,7]. HLA-DR4 and DR9 were found to be associated with RF also in American Caucasians, Arabians, and in Indians from Kashmir [10,11,12,13]. Other HLA class II antigens such as DR1, DR2, DR3, and DR6 were also found to be associated with RF/RHD in other populations [11,[14][15][16][17][18].…”

Section: Host Genetic Factorsmentioning

confidence: 99%

T Cell Response in Rheumatic Fever: Crossreactivity Between Streptococcal M Protein Peptides and Heart Tissue Proteins

Guilherme

Faé²,

Oshiro³

et al. 2007

CPPS

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Molecular mimicry between streptococcal and human proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic fever (RF) and rheumatic heart disease (RHD). In this review we focus on the studies on genetic susceptibility markers involved in the development of RF/RHD and molecular mimicry mediated by T cell responses of RHD patients against streptococcal antigens and human tissue proteins. We identified several M protein epitopes recognized by peripheral T cells of RF/RHD patients and by heart tissue infiltrating T cell clones of severe RHD patients. The regions of the M protein preferentially recognized by human T cells were also recognized by murine T cells. By analyzing the T cell receptor (TCR) we observed that some Vbeta families detected on the periphery were oligoclonal expanded in the heart lesions. These results allowed us to confirm the major role of T cells in the development of RHD lesions.

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The search for host determinants of susceptibility to rheumatic fever: the missing link. T. Duckett Jones Memorial Lecture.

Cited by 33 publications

References 15 publications

Association of class II human histocompatibility leukocyte antigens with rheumatic fever.

Association of class II human histocompatibility leukocyte antigens with rheumatic fever.

Associação do alótipo raro C4A6 do sistema complemento com a doença cardíaca reumática

T Cell Response in Rheumatic Fever: Crossreactivity Between Streptococcal M Protein Peptides and Heart Tissue Proteins

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