Derangement of apoptosis-related lymphocyte homeostasis in systemic sclerosis.
OBJECTIVE
Both increased and decreased apoptosis may be involved in generating autoimmunity. This study addressed the question of whether apoptosis and apoptosis-regulating proteins are altered in systemic sclerosis (SSc). Patients and methods. Peripheral lymphocytes of 39 SSc patients and 47 healthy control persons were studied for apoptosis, Bcl-2 and Bax levels, expression of Fas (CD95) and activation markers (CD25, HLA-DR) as determined by fluorocytometry. Serum Fas and Fas ligand were measured by ELISA.


RESULTS
SSc lymphocytes (mainly CD4(+)) expressed increased amounts of Bcl-2, while Bax was not elevated. Apoptosis rates of SSc lymphocytes were increased in unsupplemented medium, but returned to normal in the presence of autologous plasma. SSc patients had increased percentages of activated and CD95(+) lymphocytes and elevated soluble Fas and soluble FasL levels in serum. Activating anti-CD95 antibodies further increased the apoptosis rate.


CONCLUSIONS
Increased in vitro apoptosis, elevated lymphocytic Bcl-2 content and the increased number of Fas-positive T cells are not specific for peripheral blood from SSc patients, but indicate deregulation of lymphocyte homeostasis in this disease.
Stummvoll
G H
GH
Department of Rheumatology, Internal Medicine III, University of Vienna, Vienna, Austria.
Aringer
M
M
Smolen
J S
JS
Köller
M
M
Kiener
H P
HP
Steiner
C W
CW
Bohle
B
B
Knobler
R
R
Graninger
W B
WB
D000328:Adult; D000368:Aged; D017209:Apoptosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006706:Homeostasis; D006801:Humans; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D012595:Scleroderma, Systemic / Q000473:pathology / Q000503:physiopathology*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2; D051028:bcl-2-Associated X Protein