Susceptibility to Acute Rheumatic Fever

(Circulation. 2009;119:742-753.)
© 2009 American Heart Association, Inc. 

Basic Science for Clinicians

Some of the People, Some of the Time

Penelope A. Bryant; Roy Robins-Browne; Jonathan R. Carapetis; Nigel Curtis

From the Departments of Paediatrics (P.A.B., N.C.), and Microbiology and Immunology (R.R.-B.), University of Melbourne, Parkville, Australia; Infectious Diseases Unit, Department of General Medicine (P.A.B., N.C.), and Infection, Immunity and Environment Theme, Murdoch Children’s Research Institute (P.A.B., R.R.-B., N.C.), Royal Children’s Hospital Melbourne, Parkville, Australia; and Menzies School of Health Research (J.R.C.), Charles Darwin University, Casuarina, Australia.

Correspondence to Professor Nigel Curtis, University Department of Paediatrics, Royal Children’s Hospital Melbourne, Parkville, VIC 3052, Australia. E-mail nigel.curtis@rch.org.au

Acute rheumatic fever is a major cause of heart disease in large parts of the world, but it remains unknown why only a smallfraction of those who are infected with rheumatogenic group A streptococci develop an abnormal immune response that leads to acute rheumatic fever. An understanding of the mechanisms underlying host susceptibility can provide important insights into pathogenesis that in turn can inform new treatments. Extensive searches for susceptibility factors have been undertaken, including human leukocyte antigens, B-cell alloantigens, and cytokinegenes. Although significant associations have been found between genetic factors and acute rheumatic fever, study results often conflict with each other. This review explores current understanding about host susceptibility to acute rheumatic fever and provides an overall perspective to the number of studies that have recentlyaddressed this subject.