Detection of antigen in bronchial epithelium and macrophages in acute Kawasaki disease by use of synthetic antibody.
BACKGROUND
Kawasaki disease (KD) is the most common acquired cardiac disease in children in developed nations. The etiology is unknown, but a ubiquitous infectious agent appears to be likely. Immunoglobulin A plasma cells infiltrate inflamed tissues in acute KD, producing oligoclonal, antigen-driven antibodies.


METHODS
To identify antigens important in the pathogenesis of KD, oligoclonal KD antibodies were prepared in vitro and tested by immunohistochemistry experiments on tissues from patients with acute KD and from control subjects and were also tested for reactivity with human inflammatory proteins.


RESULTS
By use of synthetic antibody A, specific binding to a cytoplasmic antigen in proximal bronchial epithelium was observed in 10 of 13 patients with acute KD but in 0 of 9 control subjects (P=.001). A subset of macrophages was positive in at least 1 inflamed tissue from all 17 patients with acute KD. Antigen was detected in 9 of 12 acute KD coronary artery aneurysms but in 0 of 10 control coronary arteries (P<.001). The antigen is not immunoglobulin or any of 40 common inflammatory proteins.


CONCLUSIONS
We report the first demonstration of a KD-associated antigen in the tissues targeted by the disease. Our findings are consistent with the theory that KD is caused by a previously unidentified respiratory infectious agent with tropism for vascular tissue.
Rowley
Anne H
AH
Departments of Pediatrics and Microbiology/Immunology, Feinberg School of Medicine, Children's Memorial Hospital, Northwestern University, Chicago, Illinois 60611, USA. a-rowley@northwestern.edu
Baker
Susan C
SC
Shulman
Stanford T
ST
Garcia
Francesca L
FL
Guzman-Cottrill
Judith A
JA
Chou
Pauline
P
Terai
Masaru
M
Kawasaki
Tomisaku
T
Kalelkar
Mitra B
MB
Crawford
Susan E
SE
D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D000941:Antigens / Q000032:analysis* / Q000276:immunology; D001980:Bronchi / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics / Q000276:immunology*; D007150:Immunohistochemistry; D007223:Infant; D008264:Macrophages / Q000276:immunology; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000209:etiology / Q000276:immunology*; D043025:Oligoclonal Bands; D020545:Respiratory Mucosa / Q000276:immunology* / Q000382:microbiology; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D000941:Antigens; D007070:Immunoglobulin A; D043025:Oligoclonal Bands