Autoantibodies in the sera of patients with rheumatic heart disease: characterization of myocardial antigens by two-dimensional immunoblotting and N-terminal sequence analysis

Tontsch, Daniela; Pankuweit, Sabine; Maisch, Bernhard

doi:10.1046/j.1365-2249.2000.01283.x

Cited by 33 publications

(27 citation statements)

References 31 publications

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“…This study, like other studies described up until now (12,22,(35)(36)(37), used sera taken at the time of diagnosis before any treatment. Thus, it is reasonable to presume that such antibodies could be used as an early indicator and that the SERPA approach appears promising for discovering new potential biomarkers on the basis of autoantibody signatures (2,17,38,39).…”

Section: Serological Proteome Analysismentioning

confidence: 99%

Cancer Immunomics Using Autoantibody Signatures for Biomarker Discovery

Caron

Choquet-Kastylevsky

Joubert‐Caron

2007

Molecular & Cellular Proteomics

140

127

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The increased incidence of autoantibodies in malignancies has been described since the 1970s. Thus the ability to determine molecular fingerprinting of autoantibodies (antibody signatures) may provide useful clinical diagnostic and prognostic information. This review describes the use of several proteomics approaches for the identification of antigens recognized by these autoantibodies. Serological proteome analysis combines separation of tumor cell proteins on two-dimensional gel electrophoresis gels, Western blotting with sera of patients and healthy subjects, and identification of the detected antigens by MS. Alternatively multiple affinity protein profiling combines isolation of the antigens recognized by patient antibodies by two-dimensional immunoaffinity chromatography and identification by MS/MS. The use and limitations of reverse phase protein microarrays for testing patient serum containing autoantibodies are also considered. Lastly

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Section: Serological Proteome Analysismentioning

confidence: 99%

Cancer Immunomics Using Autoantibody Signatures for Biomarker Discovery

Caron

Choquet-Kastylevsky

Joubert‐Caron

2007

Molecular & Cellular Proteomics

140

127

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“…Rheumatogenicity of Streptococcus pyogenes strains, which are also referred to as group A streptococci (GAS), was found to correlate with certain M serotypes in different parts of the world (12)(13)(14), indicating that such M proteins may be directly involved in the pathogenesis of ARF/RHD. Different autoimmune mechanisms have been proposed for pathogenesis of ARF (3,8,15) that bases on M proteins and other surface components of GAS as causative agents and results in autoimmune response against host proteins of cardiac tissues (3,4,8,(15)(16)(17). One recent hypothesis is that human collagen IV, a major component of subendothelial basement membranes (18,19), acts as such an autoantigen after forming a complex with S. pyogenes strains, which have a potential of causing ARF (15).…”

mentioning

confidence: 99%

Identification of a Streptococcal Octapeptide Motif Involved in Acute Rheumatic Fever

Dinkla

Nitsche-Schmitz

Barroso

et al. 2007

Journal of Biological Chemistry

115

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Acute rheumatic fever is a serious autoimmune sequela of pharyngitis caused by certain group A streptococci. One mechanism applied by streptococcal strains capable of causing acute rheumatic fever is formation of an autoantigenic complex with human collagen IV. In some geographic regions with a high incidence of acute rheumatic fever pharyngeal carriage of group C and group G streptococci prevails. Examination of such strains revealed the presence of M-like surface proteins that bind human collagen. Using a peptide array and recombinant proteins with targeted amino acid substitutions, we could demonstrate that formation of collagen complexes during streptococcal infections depends on an octapeptide motif, which is present in collagen binding M and M-like proteins of different ␤-hemolytic streptococcal species. Mice immunized with streptococcal proteins that contain the collagen binding octapeptide motif developed high serum titers of anti-collagen antibodies. In sera of rheumatic fever patients such a collagen autoimmune response was accompanied by specific reactivity against the collagen-binding proteins, linking the observed effect to clinical cases. Taken together, the data demonstrate that the identified octapeptide motif through its action on collagen plays a crucial role in the pathogenesis of rheumatic fever. Eradication of streptococci that express proteins with the collagen binding motif appears advisable for controlling rheumatic fever. Acute rheumatic fever (ARF)3 is one of the most serious diseases caused by streptococci and occurs as an autoimmune sequela of untreated or inadequately treated group A streptococcal pharyngitis (1). ARF and the subsequent rheumatic heart disease (RHD) remain significant causes of cardiovascular disease today (2, 3). The most devastating effects are on children and young adults in their most productive years (2-4). According to a recent estimate more than 15 million people have RHD, more than 0.5 million acquire ARF each year, and about 0.25 million deaths annually are directly attributable to ARF or RHD (2). The fact that penicillin has clearly failed to eradicate ARF and that streptococcal vaccines are still years away from being available underlines the need for novel control strategies (5, 6). Identification of the pathogenic mechanisms underlying ARF is a prerequisite for the development of the necessary diagnostic and preventive approaches.Major virulence factors of streptococci that infect humans are the M and M-like proteins. They exert anti-phagocytic effects (7-10) and facilitate streptococcal survival within polymorph nuclear neutrophils (11). Variability in the N-terminal of M proteins generated more than 100 distinct M serotypes.

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“…Autoimmune responses against several host proteins such as cardiac myosin, heart valve glycoproteins and antigens of the sarcolemma membrane occur in ARF or RHD patients Goldstein et al, 1968;Guilherme et al, 2006;Tontsch et al, 2000;Wannamaker, 1973). Cross-reactivity of the autoantibodies with streptococcal cell wall carbohydrates, the cell membrane or the M protein was demonstrated (Kaplan and Suchy, 1964;Zabriskie and Freimer, 1966).…”

Section: Streptococcal Factors In Arfmentioning

confidence: 99%

“…The molecular and immunological processes that drive the pathogenesis of this disorder and subsequent rheumatic heart disease (RHD) have been partially discovered. Cunningham, 2012;Dinkla et al, 2003;Guilherme et al, 2006;McCarty, 1956;Stollerman, 1969;Tontsch et al, 2000;Wannamaker, 1973). The diagnostic criteria for ARF are referred to as the major Jones criteria and include arthritis, erythema, carditis and neurological dysfunctions (chorea) (Keitzer, 2005).…”

Section: Characterization Of Arfmentioning

confidence: 99%