Site-specific absence of microfibrillar-associated protein 4 (MFAP4) from the internal elastic membrane of arterioles in the rheumatoid arthritis synovial membrane: an immunohistochemical study in patients with advanced rheumatoid arthritis versus osteoarthritis

APMIS. 2019 Aug;127(8):588-593. doi: 10.1111/apm.12974.

Abstract

Microfibrillar-associated protein 4 (MFAP4) is a non-structural matrix protein with cell regulatory activities and a potential as seromarker for fibrosis. We aimed to study the occurrence of MFAP4 in the synovial membrane from patients with rheumatoid arthritis (RA) vs osteoarthritis (OA). Formaldehyde-fixed synovial tissue sections, from patients with RA (N = 6) and OA (N = 6) undergoing total hip arthroplasty, were deparaffinized and immunostained with monoclonal antibodies against MFAP4. Elastin was detected using ElastiKit. MFAP4 in serum (sMFAP4) and synovial fluid was measured by an immunoassay. MFAP4 was present in synovial biopsies from both RA and OA patients, particularly prominent in deep arterioles where it colocalized with elastin. Notably however, MFAP4 was absent from the internal elastic lamina in RA arterioles irrespective of disease duration and synovitis activity, while present although with irregular staining patterns in OA specimens. sMFAP4 was increased in RA and OA serum vs healthy controls: median (interquartile range) 29.8 (25.3-39.1) and 25.5 U/L (18.1-43.3) vs 17.7 U/L (13.7-21.2), p = 0.006 and p = 0.02, respectively The concentration of synovial fluid was lower than in serum in both RA and OA. These findings may suggest that MFAP4 is involved in adaptive vessel wall remodeling associated with chronic joint disease.

Keywords: Rheumatoid arthritis; arterioles; inflammation; microfibrillar-associated protein 4 (MFAP4); synovitis.

MeSH terms

  • Aged
  • Antibodies, Monoclonal / immunology
  • Arthritis, Rheumatoid / immunology*
  • Biomarkers / analysis
  • Carrier Proteins / analysis*
  • Carrier Proteins / immunology
  • Case-Control Studies
  • Extracellular Matrix Proteins / analysis*
  • Extracellular Matrix Proteins / immunology
  • Female
  • Glycoproteins / analysis*
  • Glycoproteins / immunology
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis / immunology*
  • Synovial Fluid / chemistry
  • Synovial Membrane / immunology*
  • Synovial Membrane / pathology

Substances

  • Antibodies, Monoclonal
  • Biomarkers
  • Carrier Proteins
  • Extracellular Matrix Proteins
  • Glycoproteins
  • MFAP4 protein, human