Nature Medicine
8, 1398 - 1404 (2002)
Published online: 18 November 2002; | doi:10.1038/nm1202-800
An immunogenetic and molecular basis for differences in outcomes of invasive group A streptococcal infectionsMalak Kotb1, 2, Anna Norrby-Teglund1, 3, Allison McGeer4, Hesham El-Sherbini1, 2, M. Tevik Dorak1, 2, Ayesha Khurshid1, 2, Karen Green4, Jeanie Peeples1, 2, Judy Wade4, Glenys Thomson5, Benjamin Schwartz6
& Donald E. Low41
Veterans Affairs Medical Center, Research Service, Memphis, Tennessee, USA
2
Departments of Surgery and Molecular Sciences, University of Tennessee, Memphis, Tennessee, USA
3
Karolinska Institutet, Center for Infectious Medicine, Huddinge University Hospital, Stockholm, Sweden
4
Department of Microbiology, Mount Sinai Hospital, and the University of Toronto, Toronto, Canada
5
Department of Integrative Biology, University of California, Berkeley, California, USA
6
Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Correspondence should be addressed to Malak Kotb mkotb@utmem.eduThe role of host genetic factors in conferring predisposition or protection in infectious diseases has become evident. Infection with group A streptococci causes a wide spectrum of disease ranging from pharyngitis to streptococcal toxic shock syndrome. The release of inflammatory cytokines triggered by streptococcal superantigens has a pivotal role in invasive streptococcal disease. However, individuals infected with the same strain can develop very different manifestations. We report here that the immunogenetics of the host influence the outcome of invasive streptococcal infection, and demonstrate the underlying mechanism for these genetic associations. Specific human leukocyte antigen class II haplotypes conferred strong protection from severe systemic disease, whereas others increased the risk of severe disease. Patients with the DRB1*1501/DQB1*0602 haplotype mounted significantly reduced responses and were less likely to develop severe systemic disease (P < 0.0001). We propose that human leukocyte antigen class II allelic variation contributes to differences in severity of invasive streptococcal infections through their ability to regulate cytokine responses triggered by streptococcal superantigens.
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