T-cell specific upregulation of Sema4A as risk factor for autoimmunity in systemic lupus erythematosus and rheumatoid arthritis

Autoimmunity. 2020 Mar;53(2):65-70. doi: 10.1080/08916934.2019.1704273. Epub 2019 Dec 26.

Abstract

The aim of the present study was to evaluate the impact of SEMA4A genetic variants on expression of sema4A protein and its relation to autoimmunity development in Systemic Lupus Erythematosus and Rheumatoid Arthritis patients. A total of 541 SLE patients, 390 RA patients and 607 healthy individuals were genotyped. We also assessed SEMA4A mRNA expression from whole blood cells and the in vitro protein production from resting and activated T lymphocytes as well as mature dendritic cells from healthy individuals stratified according to their genotypes for SLE/RA associated SEMA4A variants. Our results showed that T/T genotype for rs3738581 SNP is associated with both RA and SLE development (p = .000053, OR = 2.35; p = .0019, OR = 2.07, respectively; statistical power = 100%) and also to an increased in vitro sema4A production in active T lymphocytes. Our findings are indicative of a T cell-specific upregulation of sema4A in the presence of T/T genotype, being a risk factor for SLE and RA.

Keywords: SEMA4A; T cells; polymorphism; rheumatoid arthritis; systemic lupus erythematosus.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology
  • Autoimmunity / genetics*
  • Brazil
  • Case-Control Studies
  • Cohort Studies
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Semaphorins / genetics*
  • Semaphorins / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Up-Regulation

Substances

  • RNA, Messenger
  • SEMA4A protein, human
  • Semaphorins