Granzyme-positive cytotoxic cells are specifically increased in early rheumatoid synovial tissue.
OBJECTIVE
To define the expression and the phenotype of granzyme (Gran) A and B positive cytotoxic cells in synovial tissue (ST) from patients with rheumatoid arthritis (RA) with respect to disease duration and activity.


METHODS
Using antibodies against GranA and GranB, which serve as markers of activated natural killer (NK) cells and cytotoxic T lymphocytes, ST sections from 10 patients with early RA, 10 patients with longstanding RA, and 10 patients with osteoarthritis were examined. The phenotype of Gran+ cells was determined with double-labeling techniques.


RESULTS
Gran+ cells, the majority of which were NK cells, were found in ST from patients in all groups. Several of these cells did not express the surface markers CD16, CD56, and CD57. The highest ST expression of GranB was found in patients with early RA. In RA patients, there was a positive correlation of GranB expression with serum levels of acute-phase reactants, but not with histologic scores for inflammation.


CONCLUSIONS
Gran+ cells are mainly NK cells, a substantial proportion of which do not express conventional NK cell surface markers. GranB expression is specifically increased in the synovial tissues of patients with RA of short duration.
Tak
P P
PP
University Hospital of Leiden, The Netherlands.
Kummer
J A
JA
Hack
C E
CE
Daha
M R
MR
Smeets
T J
TJ
Erkelens
G W
GW
Meinders
A E
AE
Kluin
P M
PM
Breedveld
F C
FC
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D053804:Granzymes; D006801:Humans; D007694:Killer Cells, Natural / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000032:analysis*; D013583:Synovial Membrane / Q000201:enzymology / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology*
D002097:C-Reactive Protein; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human