IGA AND THE PATHOGENESIS OF KAWASAKI DISEASE

Abstract
Kawasaki Disease (KD) is an acute vasculitis of young childhood that may be fatal. Clinical and epidemiologic data strongly suggest an infectious cause, but the etiology of the illness remains unknown. We have reported the novel finding that IgA plasma cells infiltrate arterial tissue in acute KD. Subsequently, we found that IgA plasma cells also infiltrate proximal respiratory tract, pancreas, and kidney in acute KD. IgA plasma cells were significantly increased in the trachea of patients who died of acute KD compared to controls, similar to findings in children with fatal respiratory viral infection. These results strongly support entry of the KD etiologic agent through the upper respiratory tract, resulting in an IgA immune response, with spread through the bloodstream to arterial tissue, pancreas, and kidney. We have also determined that the IgA immune response in acute KD is oligoclonal, or antigen-driven. Oligoclonal antibody responses in affected tissues is a feature of infectious diseases. Identification of the antigens important in KD pathogenesis is urgently needed to facilitate development of a diagnostic test and improved therapy of this important pediatric illness.

Key words
Kawasaki disease, IgA, plasma cells, coronary artery, respiratory tract

Bibliografía del artículo

1. Rowley AH, Shulman ST. Kawasaki Syndrome. Pediatric Clinics of North America 1999;46:313-329.
2. Rowley AH, Gonzalez-Crussi F, Gidding SS, Duffy CE, Shulman ST. Incomplete Kawasaki Disease with Coronary Artery Involvement. Journal of Pediatrics 1987;110:409-414.
3. Newburger JW, Takahashi M, Beiser AS et al. A Single Infusion of Intravenous Gammaglobulin Compared to Four Daily Doses in the Treatment of Acute Kawasaki Syndrome. N Engl J Med 1991; 324: 1633-9.
4. Han RK, Silverman ED, Newman A, McCrindle BW. Management and Outcome of Persistent or Recurrent Fever after initial intravenous gamma globulin therapy in acute Kawasaki Disease. Arch Pediatr Adolesc Med 2000;154:694-99.
5. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 1989;244:359-64.
6. Terai M, Kohno Y, Namba M et al. Class II Major Histocompatibility antigen expression on coronary arterial endothelium in a patient with Kawasaki Disease. Hum Pathol 1990;21:231-234.
7. Fujiwara H, Hamashima Y. Pathology of the Heart in Kawasaki Disease. Pediatrics 1978;61:100-107.
8. Rowley AH, Eckerley CA, Jack HM, Shulman ST, Baker SC. IgA plasma cells in vascular tissue of patients with Kawasaki syndrome. J Immunol 1997;159:5946- 55.
9. Rowley AH, Shulman ST, Mask CA et al. IgA plasma cell infiltration of proximal respiratory tract, pancreas, kidney, and coronary artery in acute Kawasaki disease. J Infect Dis 2000;182:1183-91.
10. Bell DM, Brink EW, Nitzkin JL et al. Kawasaki Syndrome:description of two outbreaks in the United States. N Engl J Med 1981;304:1568-75.
11. Treadwell TA, Maddox RA, Holman RC et al. Investigation of Kawasaki Syndrome risk factors in Colorado. Pediatric Infectious Diseases J 2002; 21:976-78.
12. Rowley AH, Shulman ST, Spike BT, Mask CA, Baker SC. Oligoclonal IgA response in the vascular wall in acute Kawasaki Disease. J Immunol 2001;166:1334-43.
13. Brown TJ, Crawford SE, Cornwall ML, Garcia F, Shulman ST, Rowley AH. CD8 T lymphocytes and macrophages infiltrate coronary artery aneurysms in acute Kawasaki Disease. J Infect Dis 2001; 184:940-3.
14. Coloma MJ, Hastings A, Wims LA, Morrison SL. Novel vectors for the expression of antibody molecules using variable regions generated by polymerase chain reaction. J Immunological Methods 1992;152:89-104.