Scientists in China believe they have confirmed the link between matrix metalloproteinases (MMPs) and auto-immune disorders after demonstrating that levels of these enzymes are increased by up to eleven times in individuals with rheumatoid arthritis (RA).
The family of zinc-dependent proteolytic enzymes known as MMPs are key to connective tissue re-modeling and the breakdown of extra-cellular matrices during processes such as morphogenesis and angiogenesis.
Two MMPs in particular, MMP-2 and MMP-9, are often overproduced in the joints of RA patients and are thought to be involved in RA-related cartilage degeneration. However, studies attempting to confirm this have been somewhat inconsistent.
For the current study, Ming-Yuh Shiau (Hung Kuang University, Taiwan, Republic of China) and fellow researchers compared MMP levels in 44 Taiwanese individuals with RA, 22 patients with systemic lupus erythematosus, and 189 volunteers who showed no signs of an autoimmune disorder.
As published in the journal Clinical Biochemistry, plasma levels of MMP-2 were 146.1 ng/mL in the healthy volunteers but significantly higher at 194.0 ng/mL and 208.9 ng/mL in those with RA and systemic lupus erythematosus, respectively.
Concentrations of MMP-9 were similarly associated with the presence of auto-immune dysfunction, with levels of 51.4 ng/mL, 567.7 ng/mL, and 208.7 ng/mL in healthy volunteers and those with RA and systemic lupus erythematosus, respectively.
The authors comment: "It would be intriguing to identify the underlying mechanisms why both MMP-2 and MMP-9 are increased significantly in these two autoimmune diseases with different deviation of immune response."
They suggest one possible explanation based on the observation that the constitutively active transcription factor nuclear factor-κB plays a role in both RA and systemic lupus erythematosus.
Nuclear factor-κB might up-regulate production of signaling molecules, including cytokines and chemokines, that promote inflammation and, subsequently, stimulate the expression and activity of MMPs, they propose.