Dysregulation of Toll-Like Receptor Signaling-Associated Gene Expression in X-Linked Agammaglobulinemia: Implications for Correlations Genotype-Phenotype and Disease Expression.

Teocchi, Marcelo; de Andrade Eugênio, Thaís; Furlaneto Marega, Lia; Quinti, Isabella; Dos Santos Vilela, Maria Marluce

Teocchi, Marcelo; de Andrade Eugênio, Thaís; Furlaneto Marega, Lia; Quinti, Isabella; Dos Santos Vilela, Maria Marluce.

Afiliação

Teocchi M; Laboratory of Pediatric Immunology, Center for Investigation in Pediatrics, University of Campinas Medical School (FCM-UNICAMP), Campinas, Brazil.
de Andrade Eugênio T; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Furlaneto Marega L; Laboratory of Pediatric Immunology, Center for Investigation in Pediatrics, University of Campinas Medical School (FCM-UNICAMP), Campinas, Brazil.
Quinti I; Laboratory of Pediatric Immunology, Center for Investigation in Pediatrics, University of Campinas Medical School (FCM-UNICAMP), Campinas, Brazil.
Dos Santos Vilela MM; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.

J Innate Immun ; 16(1): 425-439, 2024.

Article em En | MEDLINE | ID: mdl-39116841

ABSTRACT

ABSTRACT

INTRODUCTION:

In X-linked agammaglobulinemia (XLA), the diversity of BTK variants complicates the study of genotype-phenotype correlations. Since BTK negatively regulates toll-like receptors (TLRs), we investigated if distinct BTK mutation types selectively modulate TLR pathways, affecting disease expression.

METHODS:

Using reverse transcription-quantitative polymerase chain reaction, we quantified ten TLR signaling-related genes in XLA patients with missense (n = 3) and nonsense (n = 5) BTK mutations and healthy controls (n = 17).

RESULTS:

BTK, IRAK2, PIK3R4, REL, TFRC, and UBE2N were predominantly downregulated, while RIPK2, TLR3, TLR10, and TLR6 showed variable regulation. The missense XLA group exhibited significant downregulation of IRAK2, PIK3R4, REL, and TFRC and upregulation of TLR3 and/or TLR6.

CONCLUSION:

Hypo-expression of TLR3, TLR6, and TLR10 may increase susceptibility to infections, while hyper-expression might contribute to chronic inflammatory conditions like arthritis or inflammatory bowel disease. Our findings shed light on the important inflammatory component characteristic of some XLA patients, even under optimal therapeutic conditions.

Assuntos

Tirosina Quinase da Agamaglobulinemia; Agamaglobulinemia; Estudos de Associação Genética; Doenças Genéticas Ligadas ao Cromossomo X; Transdução de Sinais; Receptores Toll-Like; Humanos; Agamaglobulinemia/genética; Agamaglobulinemia/imunologia; Doenças Genéticas Ligadas ao Cromossomo X/genética; Doenças Genéticas Ligadas ao Cromossomo X/imunologia; Tirosina Quinase da Agamaglobulinemia/genética; Transdução de Sinais/genética; Masculino; Receptores Toll-Like/genética; Receptores Toll-Like/metabolismo; Adolescente; Criança; Regulação da Expressão Gênica; Adulto; Pré-Escolar; Adulto Jovem; Feminino; Mutação

Palavras-chave

B-lymphocytes; Bruton's tyrosine kinase; Gene expression profiling; NF-kappaB; Toll-like receptor; X-linked agammaglobulinemia

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Agamaglobulinemia / Doenças Genéticas Ligadas ao Cromossomo X / Receptores Toll-Like / Estudos de Associação Genética / Tirosina Quinase da Agamaglobulinemia Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: J Innate Immun Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça

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