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Is there an Inflammation Role for MYD88 in Rheumatoid Arthritis?

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Abstract

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease with strong genetic influence, especially upon immune response components. Several cytokines from the toll-like receptors activation pathway display recognized role for RA establishment. However, few studies have verified the role of key mediators such as MYD88 gene and its genetic variants. In the present study, we aim to evaluate the rs6853 functional single-nucleotide variation (SNV) role in RA etiopathogenesis, clinical severity status, and its impact in MYD88 mRNA levels and IL-lβ protein levels. For the association study, a total of 423 RA patients and 346 health individuals, enrolled as control, from Northeast and Southeast Brazil were genotyped using specific Taqman probe. For the gene expression assays, we performed a MYD88 rs6853 genotype-guided monocyte cell culture divided into non-stimulated and lypopolysaccharides (LPS)-stimulated cells from healthy individuals. MYD88 gene expression was measured using primer specifics while IL-1β levels were evaluated by ELISA. We observed that A allele and AA genotype were associated to an increased risk to RA development (OR = 1.60; 95% CI 1.24–2.08; p = 0.0004/OR = 2.83; 95% CI 1.25–6.41; p = 0.0152). The AA genotype exhibited lower MYD88 mRNA levels than GG genotype in non-stimulated monocyte cell culture (FC − 3.83; p = 0.003). Additionally, we verified an increase of IL-1β levels when AA genotype non-stimulated monocytes were compared to AA genotype LPS-stimulates (p = 0.021). In summary, MYD88 rs6853 polymorphism associated to RA development in our Brazilian cohort and showed influence upon MYD88 mRNA levels’ expression and IL-lβ production.

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Funding

This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundação de Amparo a Ciência e Tecnologia do Estado de Pernambuco (FACEPE).

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Authors and Affiliations

  1. Department of Genetics, Federal University of Pernambuco, Rua Prof Moraes Rego, 1235, Cidade Universitária, Recife, Pernambuco, 50670-901, Brazil

    Isaura Isabelle Fonseca Gomes da Silva, Sergio Crovella, Jaqueline de Azevêdo Silva & Paula Sandrin-Garcia

  2. Laboratory of Immunopathology Keizo Asami, Recife, Pernambuco, Brazil

    Isaura Isabelle Fonseca Gomes da Silva, Camilla Albertina Dantas Lima, José Eduardo Adelino Silva, Fabricio Oliveira Souto, Sergio Crovella, Jaqueline de Azevêdo Silva & Paula Sandrin-Garcia

  3. Department of Oceanography, Federal University of Pernambuco, Recife, Pernambuco, Brazil

    Camilla Albertina Dantas Lima

  4. Division of Clinical Rheumatology, University of Pernambuco, Recife, PE, Brazil

    Eliezer Rushansky & Maria Helena Queiroz Araujo Mariano

  5. Clinical Immunology Division, Department of Medicine, Medicine Faculty of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Patrícia Rolim, Renê Donizeti Ribeiro Oliveira & Paulo Louzada-Júnior

  6. Núcleo de Ciências da Vida, Centro Acadêmico do Agreste, Federal University of Pernambuco, Recife, Pernambuco, Brazil

    Fabricio Oliveira Souto

Authors
  1. Isaura Isabelle Fonseca Gomes da Silva
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  2. Camilla Albertina Dantas Lima
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  3. José Eduardo Adelino Silva
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  4. Eliezer Rushansky
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  5. Maria Helena Queiroz Araujo Mariano
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  7. Renê Donizeti Ribeiro Oliveira
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  8. Paulo Louzada-Júnior
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  9. Fabricio Oliveira Souto
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  11. Jaqueline de Azevêdo Silva
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  12. Paula Sandrin-Garcia
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Contributions

All authors contributed to the study conception and design. Material preparation, and data collection were performed by Silva JEA, Rushansky E, Mariano MHQA, Rolim P, Oliveira RDR, and Louzada-Júnior P, and analysis were performed by Gomes-Silva IIF, Lima CA, and Silva JEA. The first draft of the manuscript was written by Gomes-Silva IIF and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Isaura Isabelle Fonseca Gomes da Silva.

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The authors declare that they have no conflict of interest.

Ethics Approval

This study was approved by Research Ethics Committee of the Federal University of Pernambuco (CAAE 43318215.9.0000.5208; CAAE 34636013.9.0000.5208).

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All participants signed a written informed consent according to the Declaration of Helsinki.

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Gomes da Silva, I.I.F., Lima, C.A.D., Silva, J.E.A. et al. Is there an Inflammation Role for MYD88 in Rheumatoid Arthritis?. Inflammation 44, 1014–1022 (2021). https://doi.org/10.1007/s10753-020-01397-5

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  • DOI: https://doi.org/10.1007/s10753-020-01397-5

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