The Absence of Evidence of Staphylococcal Toxin Involvement in the Pathogenesis of Kawasaki Disease

Terai, Masaru; Miwa, Keishi; Williams, Tommy; Kabat, William; Fukuyama, Mayumi; Okajima, Yoshitomo; Igarashi, Hideo; Shulman, Stanford T.

doi:10.1093/infdis/172.2.558

Cited by 65 publications

(40 citation statements)

References 11 publications

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“…Recently, there has been interest in a superantigen etiology of KD based upon possible selective expansion of V␤2 and V␤8 T cell receptor families in peripheral blood in acute KD (4,5); however, other investigators have been unable to confirm this finding (6 -10). Toxic shock syndrome toxin-1 or streptococcal superantigens were proposed to be related etiologically to KD based upon a single study (11) that has not been confirmed by others (7,8,(12)(13)(14).…”

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confidence: 99%

Oligoclonal IgA Response in the Vascular Wall in Acute Kawasaki Disease

Rowley

Shulman

Spike

et al. 2001

The Journal of Immunology

181

113

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Kawasaki Disease (KD) is a potentially fatal acute vasculitis of childhood. Although KD is the leading cause of acquired heart disease in children in developed nations, its pathogenesis remains unknown. We previously reported the novel observation that IgA plasma cells infiltrate the vascular wall in acute KD. We have now examined the clonality of this IgA response in vascular tissue from three fatal cases of KD to determine whether it is oligoclonal, suggesting an Ag-driven process, or polyclonal, suggesting nonspecific B cell activation or a response to a superantigen. We first sequenced VDJ junctions of 44 α genes isolated from a primary, unamplified KD vascular cDNA library. Five sets of clonally related α sequences were identified, comprising 34% (15 of 44) of the isolated α sequences. Furthermore, point mutations consistent with somatic mutation were detected in the related sequences. Next, using formalin-fixed coronary arteries from two additional fatal KD cases, we sequenced VDJ junctions of α genes isolated by RT-PCR, and a restricted pattern of CDR3 usage was observed in both. We conclude that the vascular IgA response in acute KD is oligoclonal. The identification of an oligoclonal IgA response in KD strongly suggests that the immune response to this important childhood illness is Ag-driven.

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confidence: 99%

Oligoclonal IgA Response in the Vascular Wall in Acute Kawasaki Disease

Rowley

Shulman

Spike

et al. 2001

The Journal of Immunology

181

113

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“…Of particular note in the present studies, we surveyed kinetic changes of IgM responses, which were not affected by IVIG treatment. To our knowledge, there has been only one report dealing with IgM antibodies against SAgs by Terai et al [10], who showed no evidence of significant elevation of anti-TSST-1 IgM antibodies. However, their studies set cut-off levels based on adult volunteers, and examined IgM antibody against only one SAg, i.e.…”

Section: Discussionmentioning

confidence: 90%

“…The involvement of SAgs in KD has been investigated by a variety of methods such as isolation of SAg-producing pathogens [6,8,9], selective expansion of TCR Vβ-bearing T cells in peripheral blood [3][4][5]7], and serological immune responses [10][11][12][13][14]. However, exogenous administration of immunoglobulin products can potentially limit the ability to accurately evaluate IgG responses to SAgs in KD patients.…”

Section: Discussionmentioning

confidence: 99%

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Development of serum IgM antibodies against superantigens ofStaphylococcus aureusandStreptococcus pyogenesin Kawasaki disease

Matsubara

Fukaya

Miwa

et al. 2006

Clinical and Experimental Immunology

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SummaryTo serologically determine the association of microbial superantigens and the pathogenesis of Kawasaki disease (KD), we conducted a case-control study. Serum IgG and IgM antibodies against staphylococcal enterotoxin A (SEA), SEB, SEC, toxic shock syndrome toxin-1 (TSST-1), and streptococcal pyrogenic exotoxin A (SPEA) were measured by an enzyme-linked immunosorbent assay in 293 serum samples from 65 KD patients on clinical days 1-28 and 120 control samples. The administration of immunoglobulin products, which contain high concentrations of IgG antibodies against all the superantigens, directly elevated antitoxin IgG antibodies in KD patients. In contrast, antitoxin IgM antibodies were not detected in immunoglobulin products. Actually, we found a significant elevation of IgM antibodies against SEA in KD patients in the first (median titre: 0·020, P < < < < 0·01 versus control), second (0·024, P < < < < 0·001), third (0·030, P < < < < 0·001) and fourth (0·038, P < < < < 0·001) weeks, compared to the controls (0·015). Significant differences of IgM antibodies were also true for SEB, TSST-1, and SPEA throughout the first to fourth weeks, and for SEC throughout the second to fourth weeks. The prevalence of KD patients having high IgM titres (> > > > mean + + + + 2SD of control values) to the 5 superantigens was increased with the clinical weeks, and reached 29-43% of KD subjects at the fourth week. This is the first study that describes kinetics of IgM antibodies against superantigens and clarifies the serological significance throughout the clinical course of KD. Our results suggest that multiple superantigens involve in the pathogenesis of KD.

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“…25 Efforts to identify the KD superantigen, including attempts to implicate TSST-1 as the cause, have been unrewarding. 27,28 The importance of this to the emergency physician is to realize the blurred clinical and immunologic lines that separate these diseases. The possibility that TSS and KD may occur simultaneously makes it necessary to consider instituting treatment for both diseases in certain case scenarios, as in the one presented.…”

Section: Resident Discussionmentioning

confidence: 99%

Clinicopathological Conference: Multisystem Failure in a Child

Chan

Chinnock

2000

Academic Emergency Medicine

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A 7-year-old Filipino-American female presented to the emergency department (ED) with a five-day history of lethargy, which began after a day of swimming. Four days prior to presentation, the patient had a fever to 102ЊF and abdominal pain. The parents noted ''big lymph nodes'' in her neck as well. Three days prior to presentation, the patient was seen in an ED and treated for presumptive pharyngitis with amoxicillin and ibuprofen; later that day, a truncal rash developed. On the day of presentation, the patient complained of continued fever, lethargy, anorexia, rash, and abdominal pain. She reported three days of emesis and watery diarrhea three times per day; she denied chest pain or cough. There was no past medical or surgical history. The family denied recent travel or history of tick bites.On examination, the patient was in moderate distress. The blood pressure was 68/26 mm Hg. The heart rate was 140 beats/min. Body temperature was 103.3ЊF. Room-air pulse oximetry was 98%. The head, eyes, ears, nose, and throat (HEENT) exam demonstrated bilateral scleral icterus and injection, a ''strawberry'' tongue, fissured lips, and very dry oral mucosa. On neck exam, there were large, symmetric, mobile, tender submandibular nodes. Heart rate was regular, with no murmurs or gallop. Lungs were clear to auscultation bilaterally. The abdomen was diffusely tender, but soft. Rectal exam was significant for guaiacpositive stool, but no frank blood. On pelvic exam, there was vaginal hyperemia without vaginal discharge. The skin exam showed a macular, ery-

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The Absence of Evidence of Staphylococcal Toxin Involvement in the Pathogenesis of Kawasaki Disease

Cited by 65 publications

References 11 publications

Oligoclonal IgA Response in the Vascular Wall in Acute Kawasaki Disease

Oligoclonal IgA Response in the Vascular Wall in Acute Kawasaki Disease

Development of serum IgM antibodies against superantigens ofStaphylococcus aureusandStreptococcus pyogenesin Kawasaki disease

Clinicopathological Conference: Multisystem Failure in a Child

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