Antibodies to streptococcal surface enolase react with human alpha-enolase: implications in poststreptococcal sequelae.

The pathogenic mechanisms for developing acute rheumatic fever after group A streptococcal pharyngitis are still poorly understood. The glycolytic enzyme enolase is one of the major proteins on the surface of group A streptococci. Herein, significant cross-reactivity was shown between streptococcal enolase and human enolase. Fluorocytometric analysis revealed that antistreptococcal enolase antibodies react with the enolase expressed on the surface of hematopoietic cells. Furthermore, the enolase on the leukocyte surface was found to be up-regulated by inflammatory stimuli. Evaluation of antibody titers indicated that serum samples from patients with acute rheumatic fever have higher levels of antibodies that react with the human and bacterial enolases than do serum samples from patients with streptococcal pharyngitis or healthy control subjects. These results show that streptococcal enolase is a novel cross-reactive antigen that may play an important role in the initiation of the autoimmune diseases related to streptococcal infection.

[1]  N. Rose,et al.  The role of infection in the pathogenesis of autoimmune disease. , 1998, Seminars in immunology.

[2]  J. Harley,et al.  Human monoclonal antibodies reactive with antigens of the group A Streptococcus and human heart. , 1988, Journal of immunology.

[3]  J. Zabriskie,et al.  Heart-reactive antibody associated with rheumatic fever: characterization and diagnostic significance. , 1970, Clinical and experimental immunology.

[4]  W. Telford,et al.  Postthymic development of CD28-CD8+ T cell subset: age-associated expansion and shift from memory to naive phenotype. , 1999, Journal of immunology.

[5]  S. Swedo,et al.  Case study: a new infection-triggered, autoimmune subtype of pediatric OCD and Tourette's syndrome. , 1995, Journal of the American Academy of Child and Adolescent Psychiatry.

[6]  F. Leidenberger,et al.  Autoreactive epitopes within the human alpha-enolase and their recognition by sera from patients with endometriosis. , 1995, Journal of autoimmunity.

[7]  C. Croce,et al.  Molecular cloning and nucleotide sequence of a full-length cDNA for human alpha enolase. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[8]  F. Suzuki,et al.  Immunoassay of three enolase isozymes in human serum and in blood cells. , 1983, Clinica chimica acta; international journal of clinical chemistry.

[9]  J. Zabriskie,et al.  RHEUMATIC FEVER: The Relationships Between Host, Microbe, and Genetics , 1998 .

[10]  C. Rider,et al.  Enolase isoenzymes in rat tissues. Electrophoretic, chromatographic, immunological and kinetic properties. , 1974, Biochimica et biophysica acta.

[11]  M. Caparon,et al.  A method for allelic replacement that uses the conjugative transposon Tn916: deletion of the emm6.1 allele in Streptococcus pyogenes JRS4 , 1989, Infection and immunity.

[12]  R. López-Alemany,et al.  Purification of the plasmin receptor from human carcinoma cells and comparison to α-enolase , 1994 .

[13]  M. Cunningham,et al.  Myosin: a link between streptococci and heart. , 1985, Science.

[14]  G. Seigel,et al.  Anti-enolase-alpha autoantibodies in cancer-associated retinopathy: epitope mapping and cytotoxicity on retinal cells. , 1998, Journal of autoimmunity.

[15]  M. Cunningham,et al.  Tropomyosin shares immunologic epitopes with group A streptococcal M proteins. , 1989, Journal of immunology.

[16]  S. Huber,et al.  Streptococcal M protein peptide with similarity to myosin induces CD4+ T cell-dependent myocarditis in MRL/++ mice and induces partial tolerance against coxsakieviral myocarditis. , 1996, Journal of immunology.

[17]  A. Segal,et al.  Alpha-enolase: a novel cytosolic autoantigen in ANCA positive vasculitis. , 1993, Kidney international.

[18]  S. Bombardieri,et al.  Autoantibodies specific for alpha-enolase in systemic autoimmune disorders. , 2000, The Journal of rheumatology.

[19]  D. Human,et al.  Immunological abnormalities in children with acute rheumatic carditis and acute post-streptococcal glomerulonephritis. , 1988, International journal of cardiology.

[20]  B. Manjula,et al.  Location of variable and conserved epitopes among the multiple serotypes of streptococcal M protein , 1985, The Journal of experimental medicine.

[21]  T. Quan,et al.  A surface protease and the invasive character of plague. , 1992, Science.

[22]  J. Zabriskie,et al.  Antibodies in the sera of acute rheumatic fever patients bind to human cardiac tropomyosin. , 1997, Journal of autoimmunity.

[23]  T J Walsh,et al.  Detection of circulating candida enolase by immunoassay in patients with cancer and invasive candidiasis. , 1991, The New England journal of medicine.

[24]  P. Peterson,et al.  Detection of candidal antigens in autoimmune polyglandular syndrome type I , 1996, Clinical and diagnostic laboratory immunology.

[25]  J. Flannery,et al.  The occurrence of serum autoantibodies against enolase in cancer-associated retinopathy. , 1996, Clinical immunology and immunopathology.

[26]  V. Fischetti,et al.  α-Enolase, a Novel Strong Plasmin(ogen) Binding Protein on the Surface of Pathogenic Streptococci* , 1998, The Journal of Biological Chemistry.

[27]  Miura,et al.  Circulating antibodies against α‐enolase in patients with primary membranous nephropathy (MN) , 1999 .

[28]  S. Dutta,et al.  DNA sequences encoding enolase are remarkably conserved from yeast to mammals. , 1994, Life sciences.

[29]  C. Rider,et al.  Enolase isoenzymes. III. Chromatographic and immunological characteristics of rat brain enolase. , 1976, Biochimica et biophysica acta.

[30]  J. Royds,et al.  Enolase isoenzyme distribution in the human brain and its tumours , 1982, The Journal of pathology.

[31]  L. G. Veasy,et al.  Immunologic and clinical correlations in rheumatic fever and rheumatic heart disease. , 1997, The Pediatric infectious disease journal.

[32]  N. Ganguly,et al.  Increase in activated T cells and reduction in suppressor/cytotoxic T cells in acute rheumatic fever and active rheumatic heart disease: a longitudinal study. , 1993, The Journal of infectious diseases.

[33]  M. Baker,et al.  The human ENO1 gene product (recombinant human alpha-enolase) displays characteristics required for a plasminogen binding protein. , 1997, Biochimica et biophysica acta.

[34]  M. Williams.  Rheumatic fever and the streptococcus: Another look at molecular mimicry , 1983 .

[35]  L. G. Veasy,et al.  Resurgence of acute rheumatic fever in the intermountain area of the United States. , 1987, The New England journal of medicine.

[36]  Zhao,et al.  Catalase and α‐enolase: two novel granulocyte autoantigens in inflammatory bowel disease (IBD) , 1998 .

[37]  T. Duckett Jones,et al.  THE DIAGNOSIS OF RHEUMATIC FEVER , 1944 .

[38]  P. Sundstrom,et al.  Molecular cloning of cDNA and analysis of protein secondary structure of Candida albicans enolase, an abundant, immunodominant glycolytic enzyme , 1992, Journal of bacteriology.

[39]  T. Bugge,et al.  Plasminogen Is Required for Efficient Dissemination of B. burgdorferi in Ticks and for Enhancement of Spirochetemia in Mice , 1997, Cell.

[40]  C. Gauntt,et al.  Alpha-helical coiled-coil molecules: a role in autoimmunity against the heart. , 1993, Clinical immunology and immunopathology.

[41]  B. Toh,et al.  Autoantibodies to evolutionarily conserved epitopes of enolase in a patient with discoid lupus erythematosus , 1997, Immunology.

[42]  Jordi Félez,et al.  Role of cell-surface lysines in plasminogen binding to cells: identification of alpha-enolase as a candidate plasminogen receptor. , 1991, Biochemistry.

[43]  L. G. Veasy,et al.  Serologic evidence for a class I group A streptococcal infection among rheumatic fever patients. , 1995, The Journal of infectious diseases.

[44]  M. Wessels,et al.  Relative contributions of hyaluronic acid capsule and M protein to virulence in a mucoid strain of the group A Streptococcus , 1997, Infection and immunity.

[45]  V. Fischetti,et al.  A major surface protein on group A streptococci is a glyceraldehyde-3- phosphate-dehydrogenase with multiple binding activity , 1992, The Journal of experimental medicine.

[46]  M. Cunningham,et al.  A new heart-cross-reactive antigen in Streptococcus pyogenes is not M protein. , 1990, The Journal of infectious diseases.

[47]  J. Alouf,et al.  Antibody levels and in vitro lymphoproliferative responses to Streptococcus pyogenes erythrogenic toxin A and mitogen of patients with rheumatic fever , 1991, Journal of clinical microbiology.