ADAMTS-4 as a possible distinguishing indicator between osteoarthritis and haemophilic arthropathy

Haemophilia. 2022 Jul;28(4):656-662. doi: 10.1111/hae.14569. Epub 2022 May 10.

Abstract

Introduction: Osteoarthritis (OA) and haemophilic arthropathy (HA) are clinically similar, but pathologically distinct conditions which result in joint pain and loss of function. Distinguishing their disease mechanisms is therefore a key step in the development of curative therapy, as opposed to current symptomatic treatments. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 is a metzincin-family member proteoglycan with known local involvement in OA pathogenesis.

Aim: To investigate the potential differences and discriminatory potential of ADAMTS-4 between OA and HA patients.

Methods: We determined ADAMTS-4 plasma concentrations by ELISA in patients with HA and OA. This pilot cross-sectional study included N = 40 male participants equally divided across four subgroups: haemophilia patients with severe or mild HA and control subjects with severe or mild/no OA.

Results: Our study showed a striking elevation in plasma ADAMTS-4 expression levels in HA patients as compared to OA, as well as an increase in patients with severe as compared to mild HA. By performing the binomial logistical analysis and fitting the receiver-operator curve (ROC) (cut-off probability .5), ADAMTS-4 had a sensitivity of 95% and specificity of 50% in discriminating between HA and OA among our study participants.

Conclusion: Uncovering the marked differences in plasma levels of ADAMTS-4 in patients with HA versus OA potentially sheds new light on the mechanisms of HA pathogenesis and could foster more research into the roles ADAMTS-4 and other matrix metalloproteinases (MMPs) play in HA versus OA.

Keywords: ADAMTS-4; a disintegrin and metalloproteinase with thrombospondin motifs 4; haemophilia; haemophilic arthropathy; metzincins; osteoarthritis.

MeSH terms

  • Cross-Sectional Studies
  • Humans
  • Male
  • Osteoarthritis* / complications
  • Osteoarthritis* / diagnosis