Idiopathic Dilated Cardiomyopathy

Luppi, Patrizia; Rudert, William A.; Zanone, Maria M.; Stassi, Giorgio; Trucco, Giuliana; Finegold, David N.; Boyle, Gerard J.; Nido, Pedro J. del; McGowan, Francis X.; Trucco, Massimo

doi:10.1161/01.cir.98.8.777

Cited by 54 publications

(40 citation statements)

References 46 publications

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“…In vitro, exposure of PBMC from certain healthy donors to lysates of HeLa-cells infected with CVB, was capable of selectively activating Vb7 + and Vb13.1 + T cells. These results agree with previously published data showing that variable degrees of expansion of Vb7 + and Vb13.1 + are found among proliferating and recently activated (CD69 + and/or CD71 + ) T cells from both healthy control subjects and diabetic patients cultured with CVB-infected cell lysates [40,49,50]. The presence of increased percentage of TCR Vb7 gene expression at the moment of acute EV-infections was observed in at least two of the diabetic patients.…”

Section: Discussionsupporting

confidence: 92%

“…We concluded that the activation of autoreactive T-cell clones is mediated by a mechanism which is not very specific (because more than one Vb chain is involved, i. e., Vb7 and Vb13.1) yet certainly not totally aspecific (the two chains involved are always Vb7 or Vb13.1 or both). A possible immunologic mechanism involving a superantigen was suggested previously [37,40] but other slightly different explanations can also be considered [31,32]. Apart from the true mechanism involved, it seems evident that in the majority of the cases studied, the expression of the Vb7 gene was skewed more pronouncedly than Vb13.1, so that quantitative variations of Vb7 were more easily detectable than those of Vb13.1.…”

Section: Discussionmentioning

confidence: 78%

“…The study of the TCR-Vb gene segment expression required individual amplification of at least 26 TCR-Vb families and subfamilies [40,41] using a panel of 5'-Vb primers together with a 6-carboxyfluorescein (6-FAM, Applied Biosystems, Foster City, Calif., USA) 3'-Cb oligonucleotide. The Vb and Cb oligonucleotide primers were used at a final concentration of 0.5 mmol/l each in the 50 ml final reaction mixture.…”

Section: Methodsmentioning

confidence: 99%

“…The Vb and Cb oligonucleotide primers were used at a final concentration of 0.5 mmol/l each in the 50 ml final reaction mixture. As an internal positive control for each Vb family segment, a pair of constant region oligonucleotides 5'-Ca and 3'-Ca, also tagged with 4,7,2',7'-Tetrachloro-6-carboxyfluorescein, (6-TET; Applied Biosystems), were used at a final concentration of 0.2 mmol/l [40,41]. Twenty-eight cycles of PCR were carried out to remain in the exponentially increasing part of the reaction [42].…”

Section: Methodsmentioning

confidence: 99%

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Restricted TCR Vβ gene expression and enterovirus infection in Type I diabetes: a pilot study

et al. 2000

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Type I (insulin-dependent) diabetes mellitus is an autoimmune disease characterized by infiltrating lymphocytes in the Langerhans' islets and by destruction of insulin-producing beta cells [1]. Despite many years of intensive studies, the precise cause and mechanisms triggering the beta-cell-specific attack still remain undetermined. The less than 50 % concordance for the disease between monozygotic twins suggests, however, that a complex interplay occurs between genetic and non-genetic factors (i. e., environmental) [2,3]. In particular, epidemiological evidence supports a role for infectious agents in the development and/or progression of Type I diabetes [4±10].Although the possibility of a virus-mediated etiopathogenesis of Type I diabetes still remains a central point of discussion, certain viral infections, especially Diabetologia (2000) Abstract Aims/hypothesis. High frequencies of T-cell receptor (TCR) Vb7 + T cells were detected among the lymphocytes isolated from pancreatic islets of children at the onset of Type I (insulin-dependent) diabetes mellitus. We assessed whether a preferential expression of certain TCR Vb gene families could also be detected among the peripheral blood mononuclear cells from diabetic patients. Methods. T-cell receptor repertoires were evaluated by using a semi-quantitative RT-PCR-based technique and confirmed by FACS analysis in peripheral blood mononuclear cells from diabetic patients before, at and after onset of the disease. These patients were also tested for exposure to enteroviruses by RT-PCR and by measuring titres of enterovirus-specific antibodies of the IgA, IgG, and IgM classes. Results. T-cell receptor Vb7 gene family values were higher in recently-diagnosed diabetic patients (10.5 % 3.7) than in age-matched non-diabetic control subjects (5.1 % 1.6) (p < 0.001). In a timecourse analysis of people who developed diabetes during clinical monitoring (i. e., converters), T-cell receptor Vb7 gene expression showed values consistently above 10 % (p < 0.0005). Long-standing diabetic patients showed lower percentage of Vb7 expression compared to values measured at disease onset. In the longitudinal study of the converters, multiple acute enterovirus infections were also detected. These infections appeared to be temporally related to increased percentage of Vb7 gene transcripts. Conclusion/interpretation. The deviation in the T-cell receptor Vb repertoire among circulating T cells from diabetic patients seems to re-emphasize the importance of enterovirus infections in accelerating the progression of Type I diabetes. [Diabetologia (2000) 43: 1484±1497] Keywords Type I diabetes, etiology, autoimmunity, Coxsackievirus, T cell receptor.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 78%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Restricted TCR Vβ gene expression and enterovirus infection in Type I diabetes: a pilot study

et al. 2000

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“…In addition, the in vitro exposure of peripheral blood mononuclear cells from healthy donors to the lysate of cells infected with CVB3 stimulated expansion of the same TCR V families. 15 These results suggest that a superantigen-mediated immune response is involved in human heart disease. It is noteworthy that similar clonotype expansions occur not only in our murine model of chronic ongoing myocarditis, but also in DCM patients.…”

Section: Tcrb (+) Bands With the Same Migration In The Donor And Recimentioning

confidence: 89%

Characterization of T Cell Receptor β Chains of Accumulating T Cells in Chronic Ongoing Myocarditis Demonstrated by Heterotopic Cardiac Transplantation in Mice

et al. 2001

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yocarditis is defined as an inflammatory disorder of the heart muscle and the most common etiological agents are viruses. 1 Although a link between viral myocarditis and dilated cardiomyopathy (DCM) has long been recognized, the nature of this relationship remains unclear. The progression from viral myocarditis to DCM is thought to involve autoimmunity and the presence of persistent viral infection. 2 When viral genome was detected in the myocardium of heart transplant patients with DCM, the persistent viral infection theory gained prominence. However, recent data demonstrated that the number of transplant cases with such viral infection was less than expected. 3 And in fact, abnormal immunologic responses are seen in patients with DCM; responses that include the presence of anti-heart antibodies, increased serum concentration of the soluble interleukin-2 receptor, and differences in IgG subclasses. 4 To clarify the pathogenic mechanism of these diseases, we developed a murine model of chronic ongoing viral myocarditis in Coxsackievirus B3 inoculated A/J mice. During chronic ongoing myocarditis, CD4 + T cells were found to be the main infiltrates in the myocardium. Intercellular adhesion molecule-1 (ICAM-1) was expressed on the endothelial cells of vessels in and around the infiltrated lesions. In contrast, major histocompatibility complex (MHC) class I antigen and MHC class II antigen were expressed on infected myocardial cells. More interestingly, the Coxsackievirus B3 genome was not detected in the myocardia of animals with chronic ongoing myocarditis, 5 and, moreover, we showed that myocarditis was transferred to a normal heart transplanted into a mouse with chronic ongoing myocarditis. 6 These results lead to speculation that an autoimmune response, not persistent viral infection, may play a key role in the progression of chronic ongoing myocarditis.In the present study, to prove an autoimmune mechanism of chronic ongoing myocarditis, we characterized the accumulating T cells in the donor heart that was transplanted Characterization of T Cell Receptor Chains of Accumulating T Cells in Chronic Ongoing Myocarditis Demonstrated by Heterotopic Cardiac Transplantation in MiceHiroshi Nakamura, MD; Tomohiro Kato, MD*; Taisei Yamamura, MD; Takuo Yamamoto, MD; Seiji Umemoto, MD; Taichi Sekine*; Kusuki Nishioka, MD*; Masunori Matsuzaki, MD Autoimmne mechanisms have been implicated in the pathogenesis of chronic ongoing mycarditis. An earlier study of murine chronic ongoing myocarditis reported that infiltrating T cells and macrophages were prominent in the normal donor heart, in a heterotopic cardiac transplantation model. It was demonstrated that myocarditis was transferred to a normal heart transplanted into a mouse with chronic myocarditis. The present study investigated an autoimmune link to the pathogenesis of chronic ongoing myocarditis by analyzing the T cell clonalities in the model. To characterize the accumulating T cells in the donor heart, the T cell receptor genes (TCRBG) were amplified by reverse trans...

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Enteroviruses and type 1 diabetes

Varela-Calviño¹,

Peakman²

2003

Diabetes Metabolism Res

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The development of type 1 diabetes mellitus (T1DM) has been linked to exposure to environmental triggers, with Enteroviruses (EV) historically considered the prime suspects. Early serological studies suggested a link between EV infections and the development of T1DM and, though controversial, have been bolstered by more recent studies using more sensitive techniques such as direct detection of the EV genome by RT-PCR in peripheral blood. In this review, we consider the weight of evidence that EV can be considered a candidate trigger of T1DM, using three major criteria: (1) is EV infection associated with clinical T1DM, (2) can EV trigger the development of autoimmunity and (3) what would explain the putative association?

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Idiopathic Dilated Cardiomyopathy

Cited by 54 publications

References 46 publications

Restricted TCR Vβ gene expression and enterovirus infection in Type I diabetes: a pilot study

Restricted TCR Vβ gene expression and enterovirus infection in Type I diabetes: a pilot study

Characterization of T Cell Receptor β Chains of Accumulating T Cells in Chronic Ongoing Myocarditis Demonstrated by Heterotopic Cardiac Transplantation in Mice

Enteroviruses and type 1 diabetes

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