RESUMO
Invasive group A streptococcal (GAS) disease is uncommon but carries a high case-fatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop life-threatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case-control study including 43 invasive GAS cases and 1540 controls. Using HLA imputation and linear mixed models, we find each copy of the HLA-DQA1*01:03 allele associates with a twofold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3-4.4, P = 0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.
Assuntos
Antígenos HLA/genética , Cadeias alfa de HLA-DQ/genética , Infecções Estreptocócicas/imunologia , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genes MHC da Classe II , Predisposição Genética para Doença/genética , Antígenos HLA/imunologia , Cadeias alfa de HLA-DQ/metabolismo , Haplótipos , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Streptococcus pyogenes/genética , Streptococcus pyogenes/patogenicidadeRESUMO
All who have contributed in writing this chapter have been patients and parents that have experienced an horrific life event. The horrific disease named necrotising fasciitis has affected our lives for ever. All four stories have explained how easily an everyday infection can develop incredibly quickly into a life-threatening experience. Three stories are expressed from the worn hearts of being a mother, fighting for their child every step of the way. Knowing our children and how they react through pain and illness is felt in each word, sentence, paragraph and even between the lines. Dedicating our unmarkable love and devotion for the child we carried for 9 months. To see them suffer in illness is heart wrenching, but to experience this disease necrotising fasciitis is something else. We must live through every day watching them grow with their scars of debridement, and to support them through further operations, let alone mental scars. Parents show a strength of support like no other and we hope that their lives can be enhanced through the battle they have individually won let alone their family. Robert's story from a patient's perspective is quite different and you will read his courage throughout. We continue to raise awareness through education.