Synovial fibroblasts and synovial macrophages from patients with rheumatoid arthritis and other inflammatory joint diseases show chromosomal aberrations.
Chromosomal aberrations were investigated in nuclei extracted from synovial tissue and first-passage synovial fibroblasts (P-1 SFB, 98% enrichment) or macrophages (P-1 Mphi) from patients with rheumatoid arthritis (n=10). The findings were compared with those in other rheumatic diseases (osteoarthritis, n=14; reactive arthritis, n=1), as well as with those in chronic obstructive pulmonary disease (n=8). Controls were paired peripheral blood lymphocytes from arthritic patients, synovial tissue or SFB/Mphi from joint trauma/normals (n=9), and peripheral blood monocytes from normal donors (n=10). GTG banding of metaphase chromosomes and interphase fluorescence in situ hybridization with centromere-specific probes were used. Comparable chromosomal aberrations were observed in synovial tissue and P-1 SFB of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis (polysomy 7 and aneusomies of chromosomes 4, 8, 9, 12, and 18). Notably, aneusomies of chromosomes 4, 6, 7, 8, 9, 11, 12, and/or X were also detected in P-1 synovial Mphi from rheumatoid arthritis (90% of the cases), osteoarthritis (93%), and reactive arthritis (1/1), as well as bronchial Mphi from chronic obstructive pulmonary disease (25%). No aberrations were detected in paired peripheral blood lymphocytes (except for one osteoarthritis case with a karyotype 45,X[10]/46,XX[17]), or in peripheral blood monocytes and synovial tissue of normals/joint trauma. Because Mphi aberrations were common to chronic joint and pulmonary disease, chronic inflammatory stress may induce chromosomal aberrations with potential functional relevance in local mesenchymal cells and infiltrating leukocytes in an organ-independent fashion.
Kinne
Raimund W
RW
Experimental Rheumatology Unit, Friedrich Schiller University Jena, Jena, Germany. raimund.w.kinne@rz.uni-jena.de
Kunisch
Elke
E
Beensen
Volkmar
V
Zimmermann
Thomas
T
Emmrich
Frank
F
Petrow
Peter
P
Lungershausen
Wolfgang
W
Hein
Gert
G
Braun
Rudolf K
RK
Foerster
Martin
M
Kroegel
Claus
C
Winter
Rando
R
Liesaus
Eckehard
E
Fuhrmann
Renée A
RA
Roth
Andreas
A
Claussen
Uwe
U
Liehr
Thomas
T
D000328:Adult; D000368:Aged; D000782:Aneuploidy; D016918:Arthritis, Reactive / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000473:pathology; D001980:Bronchi / Q000473:pathology; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002908:Chronic Disease; D017364:Collagenases / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007621:Karyotyping; D008171:Lung Diseases / Q000235:genetics / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*
D017364:Collagenases