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Nat Commun ; 15(1): 3795, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714679

RESUMO

The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and symptom development. We characterized cytokine production capacity before and after antibiotic treatment in 1,060 Lyme borreliosis patients. We observed a negative correlation between antibody production and IL-10 responses, as well as increased IL-1Ra responses in patients with disseminated disease. Genome-wide mapping the cytokine production allowed us to identify 34 cytokine quantitative trait loci (cQTLs), with 31 novel ones. We pinpointed the causal variant at the TLR1-6-10 locus and validated the regulation of IL-1Ra responses at transcritpome level using an independent cohort. We found that cQTLs contribute to Lyme borreliosis susceptibility and are relevant to other immune-mediated diseases. Our findings improve the understanding of cytokine responses in Lyme borreliosis and provide a genetic map of immune function as an expanded resource.


Assuntos
Citocinas , Doença de Lyme , Locos de Características Quantitativas , Doença de Lyme/imunologia , Doença de Lyme/genética , Doença de Lyme/microbiologia , Humanos , Citocinas/genética , Citocinas/metabolismo , Masculino , Feminino , Interleucina-10/genética , Adulto , Estudo de Associação Genômica Ampla , Pessoa de Meia-Idade , Proteína Antagonista do Receptor de Interleucina 1/genética , Borrelia burgdorferi/imunologia , Borrelia burgdorferi/genética , Antibacterianos , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Idoso
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