Septicemia and Shock: Pathogenesis and Novel Therapeutic Strategies
(2003, NS 124)
Anna Norrby-Teglund, Staffan Normark, Ragnar Norrby, Malak Kotb, Thierry Calandra, Terje Espevik
May 15 - 17
Nobel Forum, Karolinska Institutet, Stockholm, Sweden
Proceedings: Scandinavian Journal of Infectious Diseases, Vol. 35, No. 9, 2003, Stockholm.

 

HLA Association With Outcomes of Infectious Diseases: The Streptococcal Experience
M. Kotb^1,2, A. Norrby-Teglund^1,3, A. McGeer⁴, K. Green⁴ and D.E. Low^1
1Veterans Affairs Medical Center, Research Service, Memphis, USA, ²Departments of Surgery, and Molecular Sciences, University of TN, Memphis, USA, ³Karolinska Institutet, Center for Infectious Medicine, Huddinge University Hospital, Stockholm, Sweden,⁴Department of Microbiology, Mount Sinai Hospital, and the University of Toronto, Toronto, Canada

The Role of host genetic factors in determining susceptibility to infections has become more evident. Certain individuals appear to be predisposed to certain infections whereas others are protected. By studying the immune response and the genetic makeup of susceptible and resistant individuals a better understanding of the disease process can be achieved. Infections caused by group A streptococci offer an excellent model to study host-pathogen interactions and how the host genetic variation can influence the infection outcome. Our studies showed that the same clone of these bacteria can cause severe or nonsevere invasive disease. This difference was largely related to the HLA class II type of the patient. Certain class II haplotypes present the streptococcal superantigens in a way that results in responses whereas others present the same superantigens in a way that elicits very potent inflammatory responses that can lean to organ failure and shock. These findings underscore the role of host genetic factors in determining the outcome of serious infections and warrants further investigations into how the same or different genetic factors affect susceptiblity to other emerging and reemerging pathogens.