Invasiveness of fibroblast-like synoviocytes is an individual patient characteristic associated with the rate of joint destruction in patients with rheumatoid arthritis.
OBJECTIVE
Rheumatoid arthritis (RA) is characterized by inflammation and destruction of synovial joints. Fibroblast-like synoviocytes (FLS) harvested from synovial tissue of patients with RA can invade normal human cartilage in severe combined immunodeficient (SCID) mice and Matrigel basement membrane matrix in vitro. This study was undertaken to investigate the association of these in vitro characteristics with disease characteristics in patients with RA.


METHODS
Synovial tissue samples from 72 RA and 49 osteoarthritis (OA) patients were obtained. Samples of different joints were collected from 7 patients with RA. The FLS invasiveness in Matrigel was studied, and the intraindividual and interindividual differences were compared. From the patients with FLS who exhibited the most extreme differences in in vitro ingrowth (most and least invasive FLS), radiographs of the hands and feet were collected and scored according to the Sharp/van der Heijde method to determine the relationship between in vitro invasion data and estimated yearly joint damage progression.


RESULTS
FLS from patients with RA were more invasive than FLS from patients with OA (P < 0.001). The mean intraindividual variation in FLS invasion was much less than the mean interindividual variation (mean +/- SD 1,067 +/- 926 and 3,845 +/- 2,367 for intraindividual and interindividual variation, respectively; P = 0.035), which shows that the level of FLS invasion is a patient characteristic. The mean +/- SEM Sharp score on radiographs of the hands or feet divided by the disease duration was 4.4 +/- 1.1 units per year of disease duration in patients with the least invasive FLS (n = 9), which was much lower compared with the 21.8 +/- 3.1 units per year of disease duration in patients with the most invasive FLS (n = 9) (P < 0.001).


CONCLUSIONS
The ex vivo invasive behavior of FLS from RA patients is associated with the rate of joint destruction and is a patient characteristic, given the much smaller intraindividual than interindividual FLS variation.
Leiden University Medical Center, Leiden, The Netherlands.
Tanja C A
TC
Tolboom
Annette H M
AH
van der Helm-Van Mil
Rob G H H
RG
Nelissen
Ferdinand C
FC
Breedveld
René E M
RE
Toes
Tom W J
TW
Huizinga
D001172:Arthritis, Rheumatoid / Q000473:pathology* / Q000503:physiopathology; D001485:Basement Membrane / Q000737:chemistry / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D018450:Disease Progression; D004338:Drug Combinations; D005260:Female; D005347:Fibroblasts / Q000473:pathology* / Q000502:physiology; D006801:Humans; D007596:Joints / Q000473:pathology* / Q000503:physiopathology; D007797:Laminin / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000473:pathology / Q000503:physiopathology; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism; D013583:Synovial Membrane / Q000473:pathology* / Q000503:physiopathology
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen