An immunogenetic and molecular basis for differences in outcomes of invasive group A streptococcal infections
Autor: | Malak Kotb, Anna Norrby-Teglund, Allison McGeer, Hesham El-Sherbini, M. Tevik Dorak, Ayesha Khurshid, Karen Green, Jeanie Peeples, Judy Wade, Glenys Thomson, Benjamin Schwartz, Donald E. Low |
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Rok vydání: | 2002 |
Předmět: |
Male
Polymorphism Genetic Superantigens Streptococcus pyogenes Genes MHC Class II General Medicine HLA-DR Antigens Middle Aged General Biochemistry Genetics and Molecular Biology Haplotypes HLA-DQ Antigens Streptococcal Infections HLA-DQ beta-Chains Humans Female Fasciitis Necrotizing HLA-DRB1 Chains |
Zdroj: | Nature medicine. 8(12) |
ISSN: | 1078-8956 |
Popis: | The 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 (P0.0001). 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. |
Databáze: | OpenAIRE |
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