Analysis of TCR Vβ Repertoire and Cytokine Gene Expression in Patients with Idiopathic Dilated Cardiomyopathy

Luppi, Patrizia; Licata, Anna; Haluszczak, Catherine; Rudert, William A.; Trucco, Giuliana; McGowan, Francis X.; Finegold, David N.; Boyle, Gerard J.; Trucco, Massimo

doi:10.1006/jaut.2000.0462

Cited by 15 publications

(10 citation statements)

References 27 publications

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“…Processed antigens, in the form of short peptides, bind to a particular conformational epitope on a specific HLA antigen, which then presents the antigen to the T cell receptor complex . The recognition of self or foreign antigens is restricted by HLA class II molecules (Luppi et al 2001), which play an important role in activating immune responses and thus control the predisposition for or protection from certain diseases.…”

Section: Discussionmentioning

confidence: 99%

HLA‐DQA1, ‐DQB1 Polymorphism and Genetic Susceptibility to Idiopathic Dilated Cardiomyopathy in Hans of Northern China

Liu

Sun

2005

Annals of Human Genetics

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SummaryAutoimmune mechanisms are likely to participate in the pathogenesis of at least a subgroup of idiopathic dilated cardiomyopathy (IDC), and components of the major histocompatibility complex (MHC) may serve as markers for the propensity to develop immune-mediated myocardial damage. Human leukocyte antigen (HLA) class II genes, especially HLA-DQ genes, which are highly polymorphic, play an important role in the activation of immune responses and thus control the predisposition to, or protection from, IDC. This study was conducted to investigate the association of HLA-DQA1, -DQB1 allele polymorphisms with an autoantibody against the myocardial mitochondria ADP/ATP carrier, and to explore susceptibility to idiopathic dilated cardiomyopathy (IDC) among the Han ethnic group in northern China and the immunological mechanisms and hereditary susceptibility to IDC. Polymerase chain reaction sequence-specific primer (PCR-SSP) techniques were used to analyze polymorphisms of the second exon of HLA-DQA1 and -DQB1 alleles among 68 unrelated IDC patients, 4 probands of IDC pedigrees, and 100 healthy controls, all of Han nationality and having lived in northern China for a long time. Following echocardiography examination the IDC subjects were stratified according to ejection fraction (EF) values. Those with EF values higher than 50% were placed in subgroup 1, subgroup 2 included the patients with an EF value of 15-35%, and subgroup 3 consisted of those whose EF values were less than 15%. An autoantibody against the myocardial mitochondria ADP/ATP carrier was examined using immunoblot analysis. The frequencies of HLA-DQA1 * 0501 and HLA-DQB1 * 0303 were 0.3889 and 0.1806 in the IDC group, significantly higher than those of the healthy controls (0.0900 and 0.0364 respectively, both P < 0.05). The OR was 5.20 (95% CI: 3.60-8.50) and 4.85 (95% CI: 2.56-9.39) respectively. Further analysis of the three subgroups showed a higher frequency of HLA-DQA1 * 0501 among patients whose EF was less than 15% than those whose EF values were ≥ 15%. Conversely, the frequencies of HLA-DQA1 * 0201 and -DQB1 * 0502, * 0504 were significantly lower in the IDC group (0.0139, 0.0139 and 0.0417 respectively) than in the control group (0.2000, 0.0727 and 0.1091 respectively) (P < 0.05). The frequency of the HLA-DQA1 * 0501 allele was significantly higher in IDC patients whose autoantibody is positive in contrast with those whose autoantibody is negative (18.57% vs. 5.86%, P < 0.05); the relative risk (RR) was 4.32. The other frequencies of HLA-DQA1 and -DQB1 alleles showed no significant difference in the antibody positive and negative groups of IDC patients.

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Section: Discussionmentioning

confidence: 99%

HLA‐DQA1, ‐DQB1 Polymorphism and Genetic Susceptibility to Idiopathic Dilated Cardiomyopathy in Hans of Northern China

Liu

Sun

2005

Annals of Human Genetics

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“…For example, IFN-␥ has been detected in response to experimental cardiotropic viral infection, 21,22 and importantly, in patients with myocarditis or idiopathic dilated cardiomyopathy. 23,24 Employing IFN-␥ as an antiviral strategy succeeded in suppressing viral replication and subsequent cardiac pathology in infective myocarditis models. 25 A novel humanized nonobese diabetic (NOD)-background strain bearing the class II DQ8 allele developed spontaneous myocarditis; IFN-␥ production was associated with the propensity toward disease incidence in female mice in this model.…”

Section: Th1 Cells: Paradoxes Of Interferon ␥ and Interleukin 12mentioning

confidence: 99%

Control of inflammatory heart disease by CD4⁺ T cells

Barin

Čiháková

2013

Annals of the New York Academy of Sciences

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This review focuses on autoimmune myocarditis and its sequela, inflammatory dilated cardiomyopathy (DCMI), and the inflammatory and immune mechanisms underlying the pathogenesis of these diseases. Several mouse models of myocarditis and DCMI have improved our knowledge of the pathogenesis of these diseases, informing more general problems of cardiac remodeling and heart failure. CD4(+) T cells are critical in driving the pathogenesis of myocarditis. We discuss in detail the role of T helper cell subtypes in the pathogenesis of myocarditis, the biology of T cell-derived effector cytokines, and the participation of other leukocytic effectors in mediating disease pathophysiology. We discuss interactions between these subsets in both suppressive and collaborative fashions. These findings indicate that cardiac inflammatory disease, and autoimmunity in general, may be more diverse in divergent effector mechanisms than has previously been appreciated.

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“…Human leukocyte antigen (HLA) genes are highly polymorphic gene clusters responsible for the regulation of the immune system in humans [20–24]. HLA-DQB1 belongs to the HLA class II molecules, which are involved in activating immune responses and recognizing self or foreign antigens [25]. HLA-DQB1 plays a central role in the immune system by presenting peptides derived from extracellular proteins [26].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis

Hao

Yang²,

et al. 2017

Arthritis Res Ther

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BackgroundAnkylosing spondylitis (AS) is a chronic rheumatic and autoimmune disease. Little is known about the potential role of DNA methylation in the pathogenesis of AS. This study was undertaken to explore the potential role of DNA methylation in the genetic mechanism of AS.MethodsIn this study, we compared the genome-wide DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) between five AS patients and five healthy subjects, using the Illumina Infinium HumanMethylation450 BeadChip. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate the relevance of the identified differentially methylated genes for AS, using another independent sample of five AS patients and five healthy subjects.ResultsCompared with healthy controls, we detected 1915 differentially methylated CpG sites mapped to 1214 genes. The HLA-DQB1 gene achieved the most significant signal (cg14323910, adjusted P = 1.84 × 10–6, β difference = 0.5634) for AS. Additionally, the CpG site cg04777551 of HLA-DQB1 presented a suggestive association with AS (adjusted P = 1.46 × 10–3, β difference = 0.3594). qRT-PCR observed that the mRNA expression level of HLA-DQB1 in AS PBMCs was significantly lower than that in healthy control PBMCs (ratio = 0.48 ± 0.10, P < 0.001). Gene Ontology (GO) and KEGG pathway enrichment analysis of differentially methylated genes identified four GO terms and 10 pathways for AS, functionally related to antigen dynamics and function.ConclusionsOur results demonstrated the altered DNA methylation profile of AS and implicated HLA-DQB1 in the development of AS.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1382-1) contains supplementary material, which is available to authorized users.

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Analysis of TCR Vβ Repertoire and Cytokine Gene Expression in Patients with Idiopathic Dilated Cardiomyopathy

Cited by 15 publications

References 27 publications

HLA‐DQA1, ‐DQB1 Polymorphism and Genetic Susceptibility to Idiopathic Dilated Cardiomyopathy in Hans of Northern China

HLA‐DQA1, ‐DQB1 Polymorphism and Genetic Susceptibility to Idiopathic Dilated Cardiomyopathy in Hans of Northern China

Control of inflammatory heart disease by CD4⁺ T cells

Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis

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Analysis of TCR Vβ Repertoire and Cytokine Gene Expression in Patients with Idiopathic Dilated Cardiomyopathy

Cited by 15 publications

References 27 publications

HLA‐DQA1, ‐DQB1 Polymorphism and Genetic Susceptibility to Idiopathic Dilated Cardiomyopathy in Hans of Northern China

HLA‐DQA1, ‐DQB1 Polymorphism and Genetic Susceptibility to Idiopathic Dilated Cardiomyopathy in Hans of Northern China

Control of inflammatory heart disease by CD4+ T cells

Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis

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Control of inflammatory heart disease by CD4⁺ T cells