Is there an Inflammation Role for MYD88 in Rheumatoid Arthritis?

• Published in: Inflammation Vol. 44; no. 3; pp. 1014 - 1022
• Main Authors: Gomes da Silva, Isaura Isabelle Fonseca, Lima, Camilla Albertina Dantas, Silva, José Eduardo Adelino, Rushansky, Eliezer, Mariano, Maria Helena Queiroz Araujo, Rolim, Patrícia, Oliveira, Renê Donizeti Ribeiro, Louzada-Júnior, Paulo, Souto, Fabricio Oliveira, Crovella, Sergio, de Azevêdo Silva, Jaqueline, Sandrin-Garcia, Paula
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-06-2021; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Cell culture; Enzyme-linked immunosorbent assay; Gene expression; Gene polymorphism; Genetic diversity; Genotype & phenotype; IL-1β; Immune response; Immunology; Inflammatory diseases; Internal Medicine; Lipopolysaccharides; Monocytes; MyD88 protein; Original Article; Pathology; Pharmacology/Toxicology; Rheumatoid arthritis; Rheumatology; Toll-like receptors; SNV; myeloid differentiation protein 88; gene expression; LPS; rs6853; interleukin-1β
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-020-01397-5

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.