HLA-G may predict the disease course in patients with early rheumatoid arthritis

Hum Immunol. 2013 Apr;74(4):425-32. doi: 10.1016/j.humimm.2012.11.024. Epub 2012 Dec 8.

Abstract

The current management of early rheumatoid arthritis (ERA) is to start an intensive treatment as soon as possible. To avoid under/overtreatment, it is important to identify reliable ERA evolution biomarkers. HLA-G molecules has been associated with rheumatoid arthritis, suggesting a role in disease regulation. HLA-G antigens are expressed as membrane bound and soluble isoforms (mHLA-G, sHLA-G) that act as ligand for immune-inhibitory receptors (ILT2, ILT4, KIR2DL4). Expression of HLA-G is influenced by a 14 bp insertion/deletion polymorphism in exon 8 of the gene, where the deletion is associated with mRNA stability. We analyzed 23 ERA patients during a 12 months follow-up disease treatment for sHLA-G, IL-1beta, IL-6, IL-10 and TNF-alpha levels in plasma samples by ELISA, mHLA-G and ILT2 expression on peripheral blood CD14 positive cells by flow cytometry and typed HLA-G 14 bp deletion/insertion polymorphism by Real-Time PCR. Disease status (DAS28), ultrasonography with power Doppler and laboratory data were checked. Cytokine levels confirmed the anti-inflammatory effect of the treatment. sHLA-G, mHLA-G and ILT2 expression inversely correlated with DAS28 disease scores. The frequency of 14 bp deletion allele increased in patients with disease remission. Based on these results, HLA-G may be a candidate biomarker to evaluate early prognosis and disease activity in ERA patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Antigens, CD / blood
  • Antigens, CD / immunology
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology
  • Biomarkers / blood
  • Cytokines / blood
  • Cytokines / immunology
  • DNA Mutational Analysis
  • Early Diagnosis
  • Exons
  • Female
  • Gene Expression
  • HLA-G Antigens / blood
  • HLA-G Antigens / immunology*
  • Humans
  • Leukocyte Immunoglobulin-like Receptor B1
  • Male
  • Middle Aged
  • Mutation*
  • Prognosis
  • Protein Isoforms / blood
  • Protein Isoforms / immunology
  • Receptors, Immunologic / blood
  • Receptors, Immunologic / immunology

Substances

  • Antigens, CD
  • Biomarkers
  • Cytokines
  • HLA-G Antigens
  • LILRB1 protein, human
  • Leukocyte Immunoglobulin-like Receptor B1
  • Protein Isoforms
  • Receptors, Immunologic