title: An immunogenetic and molecular basis for differences in outcomes of invasive group A streptococcal infections.
abstract: 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 (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.
authors.affiliation: Veterans Affairs Medical Center, Research Service, Memphis, Tennessee, USA. mkotb@utmem.edu
authors.forename: Malak
authors.initials: M
authors.lastname: Kotb
authors.forename: Anna
authors.initials: A
authors.lastname: Norrby-Teglund
authors.forename: Allison
authors.initials: A
authors.lastname: McGeer
authors.forename: Hesham
authors.initials: H
authors.lastname: El-Sherbini
authors.forename: M Tevik
authors.initials: MT
authors.lastname: Dorak
authors.forename: Ayesha
authors.initials: A
authors.lastname: Khurshid
authors.forename: Karen
authors.initials: K
authors.lastname: Green
authors.forename: Jeanie
authors.initials: J
authors.lastname: Peeples
authors.forename: Judy
authors.initials: J
authors.lastname: Wade
authors.forename: Glenys
authors.initials: G
authors.lastname: Thomson
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schwartz
authors.forename: Donald E
authors.initials: DE
authors.lastname: Low
mesh_terms: D019115:Fasciitis, Necrotizing / Q000235:genetics / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013290:Streptococcal Infections / Q000235:genetics* / Q000276:immunology; D013297:Streptococcus pyogenes; D018089:Superantigens / Q000096:biosynthesis
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D018089:Superantigens