Role of Anti-Endothelial Cell Antibody in the Development of Coronary Arterial Lesions in Kawasaki Disease

BACKGROUND AND OBJECTIVES : Anti-endothelial cell antibodies (AECA) are found in the sera of many patients with Kawasaki disease (KD). In this study, the pathogenic role of AECA in the development of coronary arterial lesions of KD was investigated. SUBJECTS AND METHODS : Serum IgM-AECA concentrations were measured in 22 KD patients. Cultured human coronary artery endothelial cells (HCAEC) were incubated with either acute or convalescent phase sera, and their expressions of intercellular adhesion molecule-1 (ICAM-1) assessed. IgM fractions of the sera were purified, and their ability to induce ICAM-1 mRNA and protein expressions evaluated. To address the signal transduction pathways involved in IgM-AECA-induced ICAM-1 expression, the blocking effect of four protein kinase inhibitors, PD98059, SB203580, dimethylaminopurine (DMAP) and parthenolide were measured. RESULTS : IgM-AECA was present in 14 out of 22 (64%) acute KD sera. ICAM-1 expression of HCAEC incubated with acute KD sera (117.1+/-46.7) and AECA-positive acute KD sera (143.3+/-37.5) were significantly higher than those of the convalescent KD sera (88.9+/-14.4, p<0.05) or AECA-negative acute KD sera (71.2+/-11.8, p<0.05), respectively. IgM-AECA from KD patients significantly induced ICAM-1 protein and mRNA expression. The upregulation of ICAM-1 expression was significantly inhibited by SB203580, DMAP and parthenolide, but not by PD98059. CONCLUSION : IgM-AECA was detected in the sera of about 2/3 of acute KD patients, which activated endothelial cells by upregulation of ICAM-1 expression, possibly via p38, JNK MAPK and NF-kappaB signal transduction pathways. Thus, IgM-AECA may play a pathogenic role in the development of coronary arterial lesions in KD patients.

Clinical Observation in Children with Relapsing Minimal Change Nephrotic Syndrome

The clinical findings and follow-up data of 37 children with relapsing minimal change nephrotic syndrome were analyzed retrospectively. Among total 37 cases, 31 were male, and 6 were female. Male to female ratio was 5.2:1. All cases were admitted to the Pediatric Ward of Seoul National University Hospital more than one time, and percutaneous kidney needle biopsy which was performed during admission revealed minimal change lesion.(Kidney biopsy was done in cases with unfavorable response to initial conventional steroid therapy and/or with rather frequent relapses.) Mean age at onset was 6 5/12 years, and mean period of follow-up, 3 8/12 years. All of the patients were divided into "Initial Responder"(36 cases, 97.3%) and "Initial Nonresponder"1 case, 2.7%) according to response to steroid therapy and mode of relapse. And, the former group was subdivided into "No Relapser"(1 case, 2.7%, in this case, though no relapse was happened, persistent residual proteinuria after initial steroid therapy led to renal biopsy), "Infrequent Relapser"(18 cases, 48.6%), "Frequent Relapser"(13 cases, 35.1%), and "Subsequent Nonresponder"(4 cases, 10.8%), and the latter group, into "Late Responder"(no case) and "Continuing Nonresponder"(1case, 2.7%). In all cases, as initial symptoms, preceding URI history was detected in 32.4%, and hypertension, hematuria, and azotemia were noted in 13.5%, 10.8%, and 13.5%, respectively. Past medical history of allergy and increased serum IgE level which were suggestive of the parts of evidences for immunopathogenesis of minimal change nephrotic syndrome were found in 29.7% and 35.3%, respectively. Measuring serum levels of other immunoglobulins, IgG had a tendency of decrease, IgM, increase, IgA, variable, and IgD, normal. Among precipitating factors of relapses, URI was found most frequently(15.9%), and in 76.5% of episodes, no precipitating factor was found. Several different findings between in "Infrequent Relapser"(and in "Frequent Relapser"were observed as follows. As for age at onset, in "Infrequent Relapser" the distribution of age was diffusely scattered between 2 to 13 years, while in "Frequent Relapser" its distribution showed a decreasing tendency after initial peak incidence at 3~4 years of age. In "Frequent Relapser"(first relapse was occurred within 3 months after onset in 84.6% of cases, and within 6 months, in all, And in "Infrequent Relapser" first relapse was happened within 3 months after onset in 27.8%, within 6 months in 55.6%, and within 12 months in 94.4% of cases. In most patients of both patient groups, diuresis was initiated within 1 week after the beginning of initial steroid therapy, and loss of proteinuria was achieved within 2 weeks, which were sonewhat faster in "Infrequent Relapser"and 8 cases of "Frequent Relapser" who were followed up more than 3 years, about a half of "Infrequent Relapser" and about three fourths of "Frequent Relapser" were in active disease process with relapse(s) in the third year of follow-up. In 1 case of "Frequent Relapser" and 1 case of "Subsequent Nonresponder", cytoxan therapy was tried with good response.In most cases, several side effects due to long-term steroid therapy were discovered, but all were mild and reversible except 1 case of cataract. Through total period of follow-up in all cases, mortality was absent.