ELEVATED LEVELS OF 92-KD TYPE-IV COLLAGENASE (MATRIX-METALLOPROTEINASE-9) IN GIANT-CELL ARTERITIS

Objective. To determine if circulating gelatinase activity and matrix metalloproteinase 9 (MMP-9) (gelatinase B, or 92-kd type IV collagenas e) antigenic levels are elevated in sera of patients with giant cell a rteritis (GCA), and to ascertain if MMP-9 messenger RNA (mRNA) is depo sited in situ at sites of disease involvement. Methods. Serum samples were collected from 12 patients with GCA and 12 healthy volunteers. Va scular tissue was obtained at the time of temporal artery biopsy. Type IV collagenase activity was determined by gelatin substrate zymograph y and the quantitative biotinylated gelatin substrate degradation assa y. A double-sandwich immunoassay utilizing 2 different isotype of mono clonal antibodies generated against MMP-9 was used for measuring serum MMP-9 antigenic levels. Finally, to localize site of MMP-9 mRNA trans cription in inflamed arteries, the method of reverse transcriptase in situ polymerase chain reaction (RTisPCR) was utilized. Results. Serum gelatinase activity and MMP-9 titers were significantly increased in p atients with GCA (mean +/- SEM 198.9 +/- 36.9 mu g gelatin/hour/ml ser um, versus 21.2 +/- 4.0 in controls; P = 0.0006). The differences in a ntigenic MMP-9 levels were even more prominent (3005.4 +/- 900.6 ng/ml and 31.6 +/- 9.8 ng/ml in GCA and control sera, respectively; P = 0.0 07). By RTisPCR, MMP-9 mRNA was mainly detected in cytoplasm of cells resembling smooth muscle cells and fibroblasts in regions of fragmente d elastic tissue in the lamina media. Conclusion. Gelatinase activity, and specifically MMP-9 levels, are substantially elevated in sera of patients with GCA. Detection of MMP-9 mRNA in the lamina media of infl amed vasculature suggests that degradation of intercellular matrix, pa rticularly elastic fibers, may play a key role in the pathogenesis of GCA. Further studies are needed to determine if the circulating MMP-9 level could be utilized as a clinical marker of disease activity.