Pediatric Rheumatology Online Journal → July 2003 → Vasculitides → Kawasaki Disease → Abstract #135

POLYMORPHISMS OF COMPLEMENT COMPONENT C4 IN KAWASAKI DISEASE

B. L. Myones,¹ S. T. Shulman,² J. M. Moulds.³

Pediatric Rheumatology, Baylor College of Medicine, Houston, TX; ²Pediatric Infectious Diseases, Northwestern University School of Medicine, Chicago, IL; ³Microbiology and Immunology, MCP Hahnemann University School of Medicine, Philadelphia, PA

Several diseases characterized by complement (C) activation and C-mediated tissue damage respond to IVIG treatment. A decrease of C4d levels in Kawasaki Disease (KD) patients after IVIG treatment has been documented, coincident with decreased systemic features. C4A allotypic deficiencies (C4A Null) are over-represented in populations of patients with autoimmune diseases, who demonstrate deficient systemic clearance of circulating immune complexes. C4A deficient KD patients treated with IVIG may not bind/clear C4 fragments, thus may be poor responders and/or carry a worse prognosis. To address this issue, serum/plasma from 50 KD patients were C4 allotyped and compared with 50 pediatric controls. Data were correlated with clinical course and development of coronary artery aneurysms (CAA). C4 allotyping was performed by gel electrophoresis, immunoblot, and hemolytic overlay. The control group contained 1 complete C4A null and 8 heterozygotes, and the KD group contained 1 complete C4A null and 12 heterozygotes. The complete C4A deficient KD patient had a rapid response to IVIG, decreased C4d levels after IVIG, and did not develop CAA. 6/12 C4A heterozygotes had a rapid response to IVIG and did not develop CAA. 5/12 had a slow response to IVIG but did not develop CAA. 1/12 had a rapid response and had CAA prior to treatment. 11/37 patients with intact C4A also had a slow response to IVIG (only 1/11 with CAA). 3 KD patients were complete C4B null (all 3 had a rapid clinical response to IVIG; 1 had CAA). Of 15 C4B heterozygotes, 3/15 had a slow response to IVIG but no CAA and 12/15 had a rapid response (3/12 had CAA). 7/19 patients without deficiencies had a slow response to IVIG. There were no combined C4A/C4B deficiencies. The number of patients with CAA was insufficient to determine an association with C4 polymorphisms. Forty KD patients with persistent CAA are being allotyped to address the issue of any association with poor prognosis. In summary, although C4 null alleles were over-represented, there was no association with poor response to IVIG in KD.