(1/526) Polyclonal expansion of TCRBV2- and TCRBV6-bearing T cells in patients with Kawasaki disease.
We examined T-cell receptor (TCR) usage, cytokine production and antibody responses to superantigens in patients with Kawasaki disease (KD) to facilitate a better understanding of the immunopathogenesis of KD. The mean percentage of VB2- or VB6. 5-bearing T cells in peripheral blood mononuclear cells (PBMC) of patients with acute-phase KD was significantly higher than that of patients in the convalescent phase of KD or in healthy donors. Expansion of VB2- or VB6.5-bearing T cells was polyclonal because DNA sequences in the complementarity determining region 3 of VB2- and VB6.5-positive cDNA clones were all different from each other. The plasma levels of interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and granulocyte colony-stimulating factor (G-CSF) were elevated in the acute phase of KD. We previously reported that streptococcal pyrogenic exotoxin C (SPEC) was a potent stimulator of VB2- and VB6.5-positive T cells and, furthermore, serum levels of anti-SPEC antibodies were significantly higher in patients with acute and convalescent KD than in age-matched controls. The results of the present study, together with those of our previous report, suggest that SPEC induces activation and polyclonal expansion of VB2- and VB6.5-positive T cells, and that SPEC-induced activation of T cells may lead to the pathogenesis of KD. (+info)
(2/526) Dramatic decrease of circulating levels of monocyte chemoattractant protein-1 in Kawasaki disease after gamma globulin treatment.
Kawasaki disease (KD) is a systemic vasculitis preferentially affecting coronary arteries. Extensive monocytes/macrophages infiltrate in the vascular lesions, implying the involvement of a chemotactic cytokine in their recruitment. We investigated the role of monocyte chemoattractant protein-1 (MCP-1, also termed monocyte chemotactic and activating factor) in KD. In the immunohistochemical studies using the cardiac tissues of patients with fatal KD, MCP-1 but not interleukin (IL) -8 or macrophage inflammatory protein-1alpha was localized at the extracellular matrix associated with mononuclear cellular infiltration. The sites of MCP-1 expression correlated with the distribution of the acute inflammation, including early coronary vasculitis. In prospectively studied patients with KD, circulating levels of MCP-1, IL-8, tumor necrosis factor alpha (TNF-alpha), and IL-1alpha were elevated in 73, 77, 57, and 0% of samples before gamma globulin (GG) treatment (400 mg/kg x 5 days = total 2 g/kg), respectively, compared with respective control values. GG treatment correlated with a rapid decrease in the circulating levels of MCP-1 (P = 0.001) but not IL-8 (P = 0.19) or TNF-alpha (P = 0.33). In the sensitive Western blotting, MCP-1 bound to GG. Furthermore, GG inhibited the MCP-1-induced Ca2+ influx in a human monocytic cell line in vitro. These findings suggest a role of MCP-1 in KD, and indicate that GG treatment may block MCP-1 activity, thus alleviating KD vasculitis. (+info)
(3/526) Decreased interferon-gamma (IFN-gamma)-producing T cells in patients with acute Kawasaki disease.
Kawasaki disease (KD) is an acute febrile illness of early childhood, in which the activation of monocytes/macrophages plays a central role in the development of vasculitis during the acute stage of disease. In this study we investigated peripheral blood T cells of 10 patients with KD, focusing on the Th1 and Th2 imbalance, using intracellular cytokine staining and analysis of the cytokine-producing T cells by flow cytometry. We observed a decrease in the numbers of IFN-gamma-producing, but not IL-4-producing, CD3+ T cells, during the acute stage. Our results suggest that there is an imbalance of Th1 and Th2 subsets during the acute stage of KD. (+info)
(4/526) Anti-human cardiac myosin autoantibodies in Kawasaki syndrome.
Kawasaki syndrome (KS) is the major cause of acquired heart disease in children. Although acute myocarditis is observed in most patients with KS, its pathogenesis is unknown. Because antimyosin autoantibodies are present in autoimmune myocarditis and rheumatic carditis, the purpose of the current study was to determine whether anticardiac myosin Abs might be present during the acute stage of KS. Sera from KS patients as well as age-matched febrile controls and normal adults were compared for reactivity with human cardiac myosin in ELISAs and Western blot assays. A total of 5 of 13 KS sera, as compared with 5 of 8 acute rheumatic fever sera, contained Ab titers to human cardiac myosin that were significantly higher than those found in control sera. Both cardiac and skeletal myosins were recognized in the ELISA by KS sera, although stronger reactivity was observed to human cardiac myosin. Only IgM antimyosin Abs from KS sera were significantly elevated relative to control sera. KS sera containing antimyosin Abs recognized synthetic peptides from the light meromyosin region of the human cardiac myosin molecule and had a different pattern of reactivity than acute rheumatic fever sera, further supporting the association of antimyosin Ab with KS. These Abs may contribute to the pathogenesis of acute myocarditis found in patients with KS. (+info)
(5/526) Regulation of the expression of Fc gamma receptor on circulating neutrophils and monocytes in Kawasaki disease.
To investigate the regulation of Fc gamma receptor (Fc gamma R) expression on circulating phagocytes in Kawasaki disease (KD), we analysed the expressions of Fc gamma RI, II and III on neutrophils and monocytes in 20 patients with KD, 10 with a bacterial infection (BI), 10 with a viral infection (VI), and 10 healthy controls (HC) using flow cytometric analysis. The KD patients had a significantly higher level of Fc gamma RI expression on neutrophils, but not on monocytes, than the BI, VI and HC patients. Fc gamma RII expression on neutrophils was significantly higher in KD, BI and VI than HC, but there was no significant difference in Fc gamma RII expression among KD, BI and VI. Fc gamma RIII expression on neutrophils in KD was significantly lower than in VI and HC, but was higher on monocytes. A kinetic analysis of Fc gamma R expression in KD demonstrated the expression of Fc gamma RI and II on neutrophils to decline, but no remarkable change was observed in the monocytes, from the subacute phase through the convalescent phase. In addition, Fc gamma RIII expression on neutrophils increased, while Fc gamma RIII expression on monocytes decreased during the time course of KD. Fc gamma R expression in the acute phase of KD is thus characterized by markedly increased expression of Fc gamma RI on neutrophils, followed by a subsequent decrease, and decreased expression of Fc gamma RIII on neutrophils and increased expression of Fc gamma RIII on monocytes followed by a reverse kinetics during the clinical course. These findings are thus considered to reflect the functional up-regulation of neutrophils and monocytes in KD. (+info)
(6/526) Staphylococcus aureus isolates from patients with Kawasaki disease express high levels of protein A.
Kawasaki disease (KD) is an acute vasculitis of young children that can be complicated by coronary artery abnormalities. Recent findings suggest that a superantigen(s) may play an important role in stimulating the immune activation associated with the disease, although the origin of this superantigen(s) is unclear. Staphylococcus aureus, isolated from the rectum or pharynx of patients with KD, secretes toxic shock syndrome toxin 1 (TSST-1). The KD isolates express low levels of other exoproteins compared to isolates from patients with toxic shock syndrome (TSS). Thus, it was previously suggested that the KD isolates may be defective in the global regulatory locus agr (for accessory gene regulator), which positively regulates these factors (D. Y. M. Leung et al., Lancet 342:1385-1388, 1993). Here we describe another characteristic of KD isolates. When considered collectively, the KD isolates were found to express higher levels of staphylococcal protein A than the TSS isolates, another characteristic of an agr-defective phenotype. This correlated with a higher level of spa mRNA in these isolates. In contrast, the KD and TSS isolates expressed comparable levels of TSST-1, consistent with previous findings (D. Y. M. Leung et al., Lancet 342:1385-1388, 1993). Analysis of RNAIII transcript levels and nucleotide sequence analysis of the RNAIII-coding region suggested that the KD isolates are not defective in RNAIII, the effector molecule of the agr regulatory system. However, induction of RNAIII transcription in the KD isolates did not result in a dramatic decrease in the amount of spa mRNA, as has been reported for other strains (F. Vandenesch, J. Kornblum, and R. P. Novick, J. Bacteriol. 173:6313-6320, 1991). (+info)
(7/526) Changes in endothelium-derived vascular regulatory factors during dobutamine-stress-induced silent myocardial ischemia in patients with Kawasaki disease.
The changes in endothelium-derived vascular regulatory factors during dobutamine (DOB)-induced myocardial ischemia (MI) were investigated in 21 patients with Kawasaki disease aged from 11 months to 18 years. They were classified into an ischemia group (8 patients) and a non-ischemia group (13 patients) based on the results of 99mTc myocardial scintigraphy and DOB stress 99mTc myocardial scintigraphy. In the ischemia group, MI was relatively mild, because there were ischemic changes on the electrocardiogram and no significant symptoms during DOB stress. Catheters were positioned near the orifice of the coronary artery (Ao) and at the coronary sinus (CS). Hemodynamics and the blood concentrations of lactic acid and endothelin-1, as well as NO3-, 6-keto-prostaglandin F1alpha, and thromboxane B2, (which are inactive metabolites of nitric oxide, prostaglandin I2 and thromboxane A2, respectively), were measured at rest and after DOB stress (maximum dose: 30 microg x kg(-1) x min(-1)). The CS/Ao ratio was determined for all parameters. The rate-pressure product, an index of work load, and the cardiac index were significantly increased by DOB stress in both groups. Coronary angiography showed no vasospasm of the epicardial coronary arteries before or after DOB stress in either group. The plasma concentrations of endothelin-1 and 6-keto-prostaglandin F1alpha were significantly increased after DOB stress in the ischemia group, but the serum concentration of NO did not increase. The lack of an increase in NO production during DOB stress may have contributed to the worsening of MI in patients with Kawasaki disease. (+info)
(8/526) Kawasaki syndrome-like illness associated with infection caused by enterotoxin B-secreting Staphylococcus aureus.
Two children had symptoms and clinical signs that were characteristic of the diagnostic criteria for Kawasaki syndrome, temporally associated with Staphylococcus aureus bacteremia. One child initially had focal osteomyelitis that was evident clinically and radiographically, and radiographic evidence of multifocal osteomyelitis was noted at follow-up. The blood-borne S. aureus isolates from these two patients secreted staphylococcal enterotoxin B and were negative for toxic shock syndrome toxin. Staphylococcal and streptococcal superantigens may play a role in the pathogenesis of some cases of Kawasaki syndrome or Kawasaki syndrome-like illness. (+info)