TY - JOUR
T1 - Detection of antigen in bronchial epithelium and macrophages in acute Kawasaki disease by use of synthetic antibody
AU - Rowley, Anne H.
AU - Baker, Susan C.
AU - Shulman, Stanford T.
AU - Garcia, Francesca L.
AU - Guzman-Cottrill, Judith A.
AU - Chou, Pauline
AU - Terai, Masaru
AU - Kawasaki, Tomisaku
AU - Kalelkar, Mitra B.
AU - Crawford, Susan E.
N1 - Funding Information:
Received 29 January 2004; accepted 1 March 2004; electronically published 16 July 2004. Presented in part: Pediatric Academic Societies’ annual meeting, Seattle, 3 May 2003 (abstract 1757). Financial support: National Institutes of Health (grants HL63771 and HL67011 to A.H.R.); Kawasaki Disease Research Fund of the Children’s Memorial Hospital. A patent application for methods of use of synthetic antibody A has been submitted (A.H.R., S.C.B., and S.T.S.). Reprints or correspondence: Dr. Anne H. Rowley, Northwestern University Feinberg School of Medicine, Pediatrics W140, Ward 12-204, 303 E. Chicago Ave., Chicago, IL 60611 (a-rowley@northwestern.edu).
PY - 2004/8/15
Y1 - 2004/8/15
N2 - 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.
AB - 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.
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U2 - 10.1086/422648
DO - 10.1086/422648
M3 - Article
C2 - 15272416
AN - SCOPUS:3943074364
SN - 0022-1899
VL - 190
SP - 856
EP - 865
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -