Abstract
Streptococcal peptidoglycan causes toxic effects in experimental animals, including changes in the skin of rabbits (1-3), rheumatic-like changes in the hearts of mice (4, 5), and persistent extensive carditis in rabbits (3). No one has yet determined whether or not streptococcal peptidoglycan plays a role in rheumatic carditis in man. In order to investigate this possibility, we attempted to detect the presence of antipeptidoglycan in the sera of the rheumatic fever patients with and without carditis.
For the detection of antipeptidoglycan, we used a heterologous system involving a test antigen derived from Micrococcus lysodeikticus and inhibitors obtained from Staphylococcus aureus. The basis of reactivity of peptidoglycan with the antibody in this system is the presence of two determinants: glycan with an immunodominant β-N-acetylglucosamine (6, 7) and peptide with an immunodominant C-terminal d-alanyl-d-alanine (8, 9), presented in Table I. In the peptide determinant, l-alanyl-γ-(α-d-glutamyl)-l-lysyl-d-alanyl-d-alanine, the α-carboxyl group of d-glutamic acid is substituted by glycine in M. lysodeikticus, and by an amide in Streptococcus pyogenes and S. aureus. The glycan determinant in all three bacterial species of the test system is composed of alternating units of N-acetylglucosamine and N-acetylmuramic acid linked β-1,4.
Materials and Methods. The human sera studied for the presence of antipeptidoglycan were obtained from patients with acute rheumatic fever, patients with streptococcal impetigo, and healthy individuals. Fifteen rheumatic fever patients, seven with carditis and eight without, were under treatment at The House of The Good Samaritan. All 15 patients met the revised Jones criteria for rheumatic fever (10). Rheumatic fever patients with definitely significant murmurs were considered to have carditis; those without significant murmurs were considered not to have carditis (11). In order to provide an adequate amount of serum for the tests, it was necessary to pool several serum specimens from each patient.
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