We evaluated the inflammatory indices according to the fever duration in children with Kawasaki disease (KD), and determined duration when the inflammatory processes in KD reach their peak. Children with KD (n=152) were classified into 7 groups according to fever duration: at the third day or earlier (n=20), fourth (n=33), fifth (n=46), sixth (n=15), seventh (n=15), eighth (n=9), and at the ninth day or later after fever onset (n= 14). The levels of various laboratory indices were determined 3 times: before, 24 hr and 7 days after intravenous immunoglobulin administration (2 g/kg). WBC and neutrophil counts, and C-reactive protein level were the highest at the sixth day. Levels of hemoglobin, albumin, and high density lipoprotein cholestrol were the lowest at the sixth day. Although these indices were not significant statistically between groups, the indices showed either bell-shaped or U-shaped distribution of which peak or trench were at the sixth day. These findiugs showed that the inflammatory processes in KD reach peak on the sixth day of fever onset. This finding is important because a higher single-dose intravenous immunoglobulin treatment before the peak day may help reduce the coronary artery lesions in KD.
Child, Preschool ; Coronary Vessels/pathology ; Female ; *Fever/blood ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Infant ; *Inflammation/blood/immunology ; Male ; *Mucocutaneous Lymph Node Syndrome/blood/immunology/pathology/therapy ; Time Factors

The effect of intravenous immune globulin (IVIG) on the lymphocyte phenotypes in acute Kawasaki disease (KD) was studied in a random trial of IVIG-and-aspirin versus aspirin-alone. Before therapy, patients in each treatment group had an increased percentage of B cells, and a decreased percentage of T cells, CD4 T cells, CD8 T cells and CD5+ B cells. There was no significant difference in immunologic parameters between the two groups measured before therapy. Patients treated with IVIG-and-aspirin had by the fourth day developed a highly-significant increase in T cells, CD4 T cells and CD8 T cells and a decrease in B cells. Despite the decrease of B cells, there were significant increases in CD5+ B cells in both treatment groups. However, the degree of increase in the IVIG-and-aspirin treated group was significantly more noticeable than that in the aspirin-alone treated group. These findings indicate that treatment with IVIG restores the T- and B- cell abnormalities, especially CD5+ B-cell abnormalities found in patients with acute KD.
Child, Preschool ; Female ; Human ; Immunoglobulins, Intravenous/*therapeutic use ; Immunophenotyping ; Infant ; Lymphocyte Subsets/*immunology ; Male ; Mucocutaneous Lymph Node Syndrome/immunology/*therapy ; Support, Non-U.S. Gov't

The effect of intravenous immune globulin (IVIG) on the lymphocyte phenotypes in acute Kawasaki disease (KD) was studied in a random trial of IVIG-and-aspirin versus aspirin-alone. Before therapy, patients in each treatment group had an increased percentage of B cells, and a decreased percentage of T cells, CD4 T cells, CD8 T cells and CD5+ B cells. There was no significant difference in immunologic parameters between the two groups measured before therapy. Patients treated with IVIG-and-aspirin had by the fourth day developed a highly-significant increase in T cells, CD4 T cells and CD8 T cells and a decrease in B cells. Despite the decrease of B cells, there were significant increases in CD5+ B cells in both treatment groups. However, the degree of increase in the IVIG-and-aspirin treated group was significantly more noticeable than that in the aspirin-alone treated group. These findings indicate that treatment with IVIG restores the T- and B- cell abnormalities, especially CD5+ B-cell abnormalities found in patients with acute KD.
Child, Preschool ; Female ; Human ; Immunoglobulins, Intravenous/*therapeutic use ; Immunophenotyping ; Infant ; Lymphocyte Subsets/*immunology ; Male ; Mucocutaneous Lymph Node Syndrome/immunology/*therapy ; Support, Non-U.S. Gov't

Arthritis, Juvenile ; diagnosis ; Child ; Forecasting ; Humans ; Immunologic Tests ; Lupus Erythematosus, Systemic ; diagnosis ; Mucocutaneous Lymph Node Syndrome ; diagnosis ; Rheumatic Diseases ; diagnosis ; immunology ; therapy ; Rheumatic Fever ; diagnosis ; Scleroderma, Systemic ; diagnosis

OBJECTIVEA great deal of clinical evidence and epidemiologic data suggest that Kawasaki disease (KD) is correlated with an acute regulating imbalance of immunology. Lots of evidences in the past suggested that nuclear transcription factor-kappaB and preinflammation factors were up-regulated significantly in patients with KD. But the causative factors are still unknown. Toll-like receptors (TLRs) is a type I trans-membrane protein which could recognize ligands of pathogen microbes, activate the nuclear transcription factor-kappaB and promote gene transcription of pre-inflammation factors and co-stimulatory molecules on cell surface. Aberrant activation of signal pathway of TLRs could interfere with autoimmune tolerance and cause autoimmune diseases. The study was designed to investigate the role of signal transduction of TLRs on immunological pathogenesis of KD.

METHODSSixteen children with KD and 16 age-matched health children were studied. Reverse-transcription PCR (RT-PCR) and real-time PCR were used to evaluate the levels of TLRs 1 - 10, MD-2, MyD88, IL-1beta, IL-6 and IL-8 mRNA expressions in peripheral blood mononuclear cells, and expressions of TLRs 2, 4 and co-stimulatory molecules such as CD80 and CD86 in monocyte/macrophage were analyzed by flow cytometry.

RESULTS(1) Compared with control group, the protein and mRNA levels of TLR4 in KD group were up-regulated significantly [(Real-time PCR: 325.22 +/- 50.34 vs. 2.20 +/- 0.23, P < 0.01); (flow cytometry: 15.96% +/- 5.94% vs. 3.21% +/- 0.62%, P < 0.01)], the difference being not significant as to other TLRs. (2) Transcriptional levels of MD-2 and Myd88 were significantly up-regulated in acute phase of KD (P < 0.01), and down-regulated after the treatment with intravenous gamma globulin therapy. (3) Expressions of co-stimulatory molecules and cytokines in monocyte/macrophage during acute phase of KD were higher than those of control group (P < 0.01).

CONCLUSIONExpressions of TLRs 4, MD-2 and Myd88 were up-regulated during acute phase in KD, suggesting that aberrant activation of TLRs 4 might be one of the initiating factors of immune aberrance in KD.

Case-Control Studies ; Child, Preschool ; Female ; Flow Cytometry ; Humans ; Immunoglobulins, Intravenous ; immunology ; therapeutic use ; Immunologic Factors ; immunology ; therapeutic use ; Infant ; Leukocytes, Mononuclear ; drug effects ; immunology ; metabolism ; Male ; Mucocutaneous Lymph Node Syndrome ; drug therapy ; immunology ; Myeloid Differentiation Factor 88 ; genetics ; metabolism ; RNA, Messenger ; Reverse Transcriptase Polymerase Chain Reaction ; Toll-Like Receptor 4 ; genetics ; metabolism ; Toll-Like Receptors ; genetics ; metabolism ; Up-Regulation ; drug effects

OBJECTIVEThe study was designed to investigate the changes in CD(69), CD(25) and HLA-DR expressions in peripheral blood T cell in Kawasaki disease (KD).

METHODSThe authors detected CD(69), CD(25) and HLA-DR expressions in peripheral blood T cell by using flow cytometry. The patients who met the diagnostic criteria for KD comprised sixteen boys and fifteen girls (4 - 60 months of age; mean, 26 +/- 18 months). All received intravenous gammaglobulin at a dose of 1 g/(kg.d), for 2 days and oral aspirin at a dose of 30 - 50 mg/(kg.d). In case of persistent fever, a repeated dose of intravenous gammaglobulin or I.V. methylprednisolone at a dose of 20 mg/(kg.d) for three daily doses was attempted. The authors tested blood samples from 17 healthy controls consisting of nine boys and eight girls (3 - 84 months of age; mean, 25 +/- 18 months) and the samples from 31 patients.

RESULTSThe percentage of peripheral blood CD(3)(+) T lymphocyte was (54.4 +/- 9.0)% in acute stage of KD and (65.0 +/- 7.0)% in healthy controls. There was a significant difference between the two groups (P < 0.001). The values of CD(69)(+) [(11.2 +/- 12.6)%, vs. (0.6 +/- 0.4)%], CD(25)(+) [(9.2 +/- 3.5)% vs. (3.9 +/- 1.8)%] and HLA-DR(+) [(8.3 +/- 5.0)% vs. (4.3 +/- 2.3)%] in KD patients were markedly increased compared to those of the healthy controls. After intravenous gammaglobulin treatment, the percentage of CD(3)(+)CD(69)(+) and CD(3)(+)CD(25)(+) significantly decreased [CD(3)(+)CD(69)(+): (14.0 +/- 13.0)% vs. (1.6 +/- 1.2)%, P < 0.05; CD(3)(+)CD(25)(+): (7.8 +/- 4.1)% vs. (2.0 +/- 0.6)%, P < 0.01]. However, the CD(3)(+) T lymphocytes increased [(50.8 +/- 5.0)% vs. (64.9 +/- 5.5)%, P < 0.01]. There was no significant difference in expression of CD(3)(+) T lymphocyte cell activating markers between coronary artery disease group and normal coronary artery group in KD cases (P > 0.05).

CONCLUSIONCD(3)(+) T cell activation in the early and middle stages is involved in the mechanism responsible for cardiovascular injury.

Antigens, CD ; blood ; Antigens, Differentiation, T-Lymphocyte ; blood ; Aspirin ; administration & dosage ; therapeutic use ; Biomarkers ; blood ; Child, Preschool ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Flow Cytometry ; Glucocorticoids ; therapeutic use ; HLA-DR Antigens ; blood ; Humans ; Immunoglobulins, Intravenous ; therapeutic use ; Immunologic Factors ; therapeutic use ; Infant ; Interleukin-2 Receptor alpha Subunit ; blood ; Lectins, C-Type ; blood ; Male ; Methylprednisolone ; therapeutic use ; Mucocutaneous Lymph Node Syndrome ; blood ; diagnosis ; drug therapy ; immunology ; Platelet Aggregation Inhibitors ; therapeutic use ; Prognosis ; T-Lymphocytes ; drug effects ; immunology ; Treatment Outcome