Possible Role of <i>Streptococcus pyogenes</i> in Mucocutaneous Lymph Node Syndrome VIII. Immunological Tolerance to <i>S. pyogenes‐</i>Associated Antigens Seems Essential to Induction of MCLS

Osawa, Naoya; Yarnaura, Noboru; Ikewaki, Nobunao; Yashiro, Kimio; Akiyarna, Takehisa

doi:10.1111/j.1442-200x.1989.tb01333.x

Pediatrics International

1989

DOI: 10.1111/j.1442-200x.1989.tb01333.x

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Possible Role of Streptococcus pyogenes in Mucocutaneous Lymph Node Syndrome VIII. Immunological Tolerance to S. pyogenes‐Associated Antigens Seems Essential to Induction of MCLS

Naoya Osawa

Noboru Yarnaura

Nobunao Ikewaki

et al.

Abstract: In our previous studies, we attempted to show that new‐born mice infected with an attenuated strain of Streptococcus pyogenes, and exposed to streptococcal antigens approximately one month later, failed to develop a humoral response to those antigens but were able to respond normally to other unrelated antigens. Since such immunological characteristics are identical to those of patients with the mucacutaneous lymph node syndrome (MCLS), the present studies were performed with the aim of assessing the antibody‐… Show more

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Cited by 5 publications

References 7 publications

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Probable role ofStreptococcus pyogenes in Kawasaki disease

Akiyama

Yashiro

1993

Eur J Pediatr

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Over the past 25 years, the clinical course of Kawasaki disease has been defined, the prevalence and nature of the cardiovascular effects widely understood, and pathological changes in the most severe cases well described. However, the aetiology and pathogenesis of this puzzling disease have remained unclear, thus specific therapy is not yet available. Because of some close clinical similarities between this disease and streptococcal scarlet fever, particular attention has been paid to the possible role of Streptococcus pyogenes as an aetiological agent in this illness. Until now, however, group A beta-haemolytic streptococci have never been consistently isolated from any patients; in addition, the titre of anti-streptolysin 0 is not raised, and lack of response to antibiotics is a feature of this disease. Our long series of investigations over more than 10 years, which will be covered in the present review, were performed in an attempt at elucidating causative agent(s) of Kawasaki disease. This has led to our firm belief in the probable role of S. pyogenes in the pathogenesis of this disease, despite the lack of fulfillment of Koch's postulates, on the basis of the following findings. Patients with Kawasaki disease recovering from the acute, febrile phase of the illness exhibited an exaggerated cell-mediated reactivity, as measured by the macrophage migration inhibition test, to group A beta-haemolytic streptococci, their pyrogenic exotoxin and streptolysin 0 as well as to several mammalian muscle cell extracts which are allegedly related antigenically to the cell wall and/or cytoplasmic membrane of S. pyogenes. Protoplast-like "spherical bodies" varying in diameter from 0.5 to 1.5 microns, and devoid of cell walls, were detected in the buffy coats of peripheral blood from patients with this disease, and stained distinctly by immuno-electron microscopy using, as a primary antibody, a rabbit antiserum to S. pyogenes- derived protoplasts, and followed by absorption with protoplasts from Staphylococcus aureus and Escherichia coli. Newborn mice infected with S. pyogenes having no capacity to confer cell-mediated immunity even in adult murine hosts, and reinfected 4-6 weeks later with another strain of the same species of bacteria which is able to elicit cellular immunity, showed a lack of humoral response to streptococcal antigens, leaving intact cell-mediated immunity. Such a biased immunological characteristic is an exact counterpart of that of Kawasaki disease patients.(ABSTRACT TRUNCATED AT 400 WORDS)

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Probable role ofStreptococcus pyogenes in Kawasaki disease

Akiyama

Yashiro

1993

Eur J Pediatr

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Possible Role of Streptococcus pyogenes in Mucocutaneous Lymph Node Syndrome IX. Quantitation by ELISA of Streptococcal Pyrogenic Exotoxin in the Serum of MCLS Patients

Kawai

Osawa

Yamaura

et al. 1989

Pediatrics International

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In the present paper we describe the use of an enzyme‐linked immunosorbent assay reinforced with an introduction of monoclonal antibody, for the detection and quantitation of streptococcal pyrogenic exotoxin (SPE) in the serum of patients with mucocutaneous lymph node syndrome (MCLS). The amount of SPE was usually at a high level, and its 100% incidence in patients' sera was proved whenever the assay was made on the day of admission, thereby showing a marked contrast to carefully matched control sera which failed to mediate any positive result. As for the change in detected amount of the toxin, a clear dichotomy was observed between the serum of gammaglobulin‐treated patients and that of infants given aspirin; in the former the positive result turned to negative rapidly following the initiation of treatment coupled with a defervescence, while in the latter the reduction of SPE levels was scarcely monitored for as long as 17 days after the onset of illness. Quantitation of SPE might be an auxiliary test for the diagnosis of MCLS, because a considerable amount of SPE was assessed in a patient who developed characteristic huge coronary artery aneurysms following an illness which did not fulfill the diagnostic criteria. These findings support our speculation in relation to the certain role of S. pyogenes as an etiological agent for MCLS. The possible mechanisms of gammaglobulin treatment in reducing the prevalence of cardiovascular lesions and the duration of systemic inflammation are discussed.

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Possible Role of Streptococcus pyogenes in Mucocutaneous Lymph Node Syndrome XL Immunoelectron Microscopic Observation of Protoplast‐like “Spherical Bodies” Detected in Peripheral Blood of MCLS Patients

Akiyama¹,

Tamauchi²,

Nakazato³

et al. 1991

Pediatrics International

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Protoplast‐like “spherical bodies” averaging 0.5‐1.5mU m in diameter and devoid of cell walls were first detected by Ueno et al, in the buffy coat of heparinized venous blood from patients with mucocutaneous lymph node syndrome (MCLS). But the nature of the “bodies” has yet to be clarified because of the absence of convincing evidence pointing to their antigenic characteristics. The present investigations were designed solely to provide a serological identification of the “bodies” by the use of immunoelectron microscopy, with the following results. First, “spherical bodies” bearing a striking resemblance to those observed by the above‐mentioned authors were detected in biopsy specimens from challenge sites in mice infected with Streptococcus pyogenes as well as in the buffy coat of peripheral blood from MCLS patients. Second, the “bodies” detected were stained distinctly in both cases by an immunohistochemical technique using, as the primary antibody, a rabbit antiserum raised toward S. pyogenes‐derhed protoplasts, which was then absorbed with protoplasts from Staphylococcus aureus and Escherichia coti. Third, the absorbed sera were proved to be not faultless, because complete specificity toward protoplasts from S. pyogenes was not attained due to the presence of a large amount of cross‐reactive antigens between protoplasts from the immunizing and absorbing strains of bacteria. The implications of these findings are discussed, particularly in relation to the evaluation of the present serological test for the “spherical bodies.”

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Possible Role of Streptococcus pyogenes in Mucocutaneous Lymph Node Syndrome VIII. Immunological Tolerance to S. pyogenes‐Associated Antigens Seems Essential to Induction of MCLS

Cited by 5 publications

References 7 publications

Probable role ofStreptococcus pyogenes in Kawasaki disease

Probable role ofStreptococcus pyogenes in Kawasaki disease

Possible Role of Streptococcus pyogenes in Mucocutaneous Lymph Node Syndrome IX. Quantitation by ELISA of Streptococcal Pyrogenic Exotoxin in the Serum of MCLS Patients

Possible Role of Streptococcus pyogenes in Mucocutaneous Lymph Node Syndrome XL Immunoelectron Microscopic Observation of Protoplast‐like “Spherical Bodies” Detected in Peripheral Blood of MCLS Patients

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