Asymptomatic synovitis precedes clinically manifest arthritis.
OBJECTIVE
It has been hypothesized that asymptomatic synovitis may precede clinical manifestations of arthritis in the earliest phase of rheumatoid arthritis (RA). To obtain more insight into this disease phase, we investigated the immunohistologic features of synovial tissue (ST) from the knee joints of rhesus monkeys with induced arthritis and from RA patients with both clinically involved and clinically uninvolved knee joints.


METHODS
Serial ST biopsy specimens from the knee joints of 4 rhesus monkeys that had been immunized with type II collagen and ST from 10 RA patients were investigated. Eight patients without inflammatory joint disease served as controls.


RESULTS
In ST from immunized monkeys, an influx of macrophages was observed well before the occurrence of arthritis. Signs of inflammation were also demonstrated in ST from clinically uninvolved knee joints of all RA patients evaluated. The ST was characterized in particular by infiltration with macrophages and by the expression of macrophage-derived cytokines.


CONCLUSIONS
The findings support the view that asymptomatic synovitis precedes clinically manifest arthritis in both early and established RA. This implies that the debut of RA already represents a chronic phase of the disease.
Leiden University Medical Center, The Netherlands.
M C
MC
Kraan
H
H
Versendaal
M
M
Jonker
B
B
Bresnihan
W J
WJ
Post
B A
BA
t Hart
F C
FC
Breedveld
P P
PP
Tak
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000276:immunology / Q000473:pathology; D017252:CD3 Complex / Q000032:analysis; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007719:Knee Joint / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008253:Macaca mulatta; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013585:Synovitis / Q000150:complications* / Q000276:immunology / Q000473:pathology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D016207:Cytokines; C067980:CD68 antigen, human; D000097382:CD68 Molecule