Identification of Cardiac Autoantigens in Human Heart CDNA Libraries Using Acute Rheumatic Fever Sera

Qg, Eichbaum; Dw, Beatty; Mi, Parker

doi:10.1006/jaut.1994.1019

Cited by 9 publications

(4 citation statements)

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“…We have also demonstrated the presence of mRNA for the AC-activating proteins G s large and G s small, using primers designed to be complementary to a cardiac autoantigen homologous to G s (Eichbaum et al 1994). This confirms our previous data obtained utilising a different set of PCR primers (Europe-Finner et al 1996), and establishes the presence of multiple possible G s-AC pathways in human myometrium.…”

Section: Figuresupporting

confidence: 88%

Adenylyl cyclase isoforms in pregnant and non-pregnant human myometrium

Price

Pochun²,

Phaneuf³

et al. 2000

Journal of Endocrinology

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The precise factors involved in the transition of the relaxed pregnant uterus to the contractile state at the onset of parturition remain unclear, but it is accepted that cAMPgenerating pathways contribute to uterine relaxation. We have previously reported an increased expression of the adenylyl cyclase (AC)-stimulating protein G s in human myometrium during gestation, with a corresponding increase in GTP-stimulated AC activity. However, little is known about the predominating AC isoforms expressed during pregnancy. This information is important, because although all AC isoforms are stimulated by G s, their regulation by other signalling molecules is very different. In the present study we have identified the isoforms of AC expressed in both pregnant and non-pregnant myometrium by mRNA analysis and immunoblotting. mRNA encoding for AC I, II, III, VIII and IX was present in non-pregnant and pregnant myometrium, and in cultured myometrial cells. Differing levels of AC protein could be detected in myometrial plasma membranes, with decreased levels of Group 1 (isoforms I, III and VIII) and Group 4 (IX) ACs allied with increased levels of Group 2 (II, IV and VII) and 3 (V and VI) ACs during pregnancy. These findings imply a role for Group 2-activating pathways, e.g. G-protein -subunits and protein kinase C, in the maintenance of uterine quiescence, whilst suggesting a lesser involvement of calcium-calmodulin complex, an activator of Group 1 AC isoforms, in uterine relaxation during gestation. These data may provide an alternative pharmacological approach for the attenuation of preterm labour.

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Section: Figuresupporting

confidence: 88%

Adenylyl cyclase isoforms in pregnant and non-pregnant human myometrium

Price

Pochun²,

Phaneuf³

et al. 2000

Journal of Endocrinology

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“…10 A similar argument has been made for bacterial antigens, especially in ankylosing spondylitis 11 and rheumatic fever heart disease. 12 Bacterial heat shock proteins, especially Hsp65 from mycobacteria, are popular candidates for the relevant mimic molecules. In fact, patients with autoimmune hepatitis have significantly higher levels of anti-Hsp65 and anti-human superoxide dismutase antibodies compared with patients with chronic active hepatitis C, systemic lupus erythematosus (SLE), or normal controls.…”

Section: Infectious Agents and Molecular Mimicrymentioning

confidence: 99%

Molecular Mimicry and Primary Biliary Cirrhosis: Premises Not Promises

et al. 2001

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“…This study differs from other studies in that it utilizes a commercially available λTriplEx2 long insert library (Clontech, USA: Cat: HL5506u). This library is superior to those used in earlier studies 16 because of the ability to express in all three forward‐reading frames. In addition, the long inserts increase the probability of expressing the entire cross‐reactive antigen.…”

Section: Methodsmentioning

confidence: 92%

“…Other candidate cardiac autoantigens have been identified. An earlier heart cDNA library study identified cytokeratin, adenyl cyclase, and a third unknown protein 16 later identified as RAD23. A 2D‐PAGE study of myocardial proteins also identified a creatine kinase and two mitochondrial proteins that were reactive with ARF sera 17 .…”

Section: Introductionmentioning

confidence: 99%

Autoantigens Identified by Screening a Human Heart cDNA Library with Acute Rheumatic Fever Sera

Towers

Bolm

Currie

et al. 2009

Annals of the New York Academy of Sciences

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Acute rheumatic fever (ARF) is an autoimmune sequela of group A streptococcal infection mostly affecting school-aged children. Recurrent episodes of ARF can result in the development of rheumatic heart disease (RHD). One in 40 indigenous Australians in the Northern Territory is affected by RHD. This disease mostly impacts young people; 45% of those who require heart valve surgery in Australia due to RHD are younger than 25 years old. ARF is characterized by autoimmune attack of the heart; therefore, the presence of the autoantibodies involved could potentially be used to diagnose ARF. To this end, a human heart cDNA library was screened with serum from a patient with ARF, and 12 autoreactive human heart antigens were identified. They include five different IgG heavy chains and a range of tissue-specific cell-signaling proteins, species of which have been implicated in other autoimmune diseases. Preliminary ELISA results show that ARF patients have significantly higher levels of antibodies recognizing the cardiac autoantigens than controls. These antigens are promising candidates for the development of a serological assay for the diagnosis of ARF. The nature of the proteins identified has exciting implications for future research into the pathogenesis of ARF.

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Identification of Cardiac Autoantigens in Human Heart CDNA Libraries Using Acute Rheumatic Fever Sera

Cited by 9 publications

References 0 publications

Adenylyl cyclase isoforms in pregnant and non-pregnant human myometrium

Adenylyl cyclase isoforms in pregnant and non-pregnant human myometrium

Molecular Mimicry and Primary Biliary Cirrhosis: Premises Not Promises

Autoantigens Identified by Screening a Human Heart cDNA Library with Acute Rheumatic Fever Sera

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