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Apoptosis of CD34 cells after incubation with sera of leukopenic patients with systemic lupus erythematosus

Department of Nephrology, University of Innsbruck, Innsbruck, Austria, martin.tiefenthaler{at}uibk.ac.at

N Bacher

Department of Internal Medicine, University of Innsbruck, Innsbruck, Austria

H Linert

Department of Internal Medicine, University of Innsbruck, Innsbruck, Austria

O Mühlmann

Department of Internal Medicine, University of Innsbruck, Innsbruck, Austria

S Hofer

Department of Dermatology, University of Innsbruck, Innsbruck, Austria

N Sepp

Department of Dermatology, University of Innsbruck, Innsbruck, Austria

A Amberger

Tiroler Krebsforschungzentrum, Innsbruck, Austria

F Geisen

Department of Hematology, University of Innsbruck, Innsbruck, Austria

G Obermoser

Department of Dermatology, University of Innsbruck, Innsbruck, Austria

G Konwalinka

Department of Internal Medicine, University of Innsbruck, Innsbruck, Austria

Leukopenia and anaemia are observed in about a fifth of all patients with systemic lupus erythematosus (SLE) and may be due either to the destruction of blood cells or their decreased production. The former may be humoral or cell-mediatedor result from apoptosis of peripheral blood cells. Several observations suggest the occurrence of the latter: reduced in vitro proliferation of pluripotentbone marrow progenitorsfrom the bone marrow aspirates of SLE patients, reduced counts of CD34 cells in bone marrow aspiratesin SLE patients, apoptosisof lymphopoieticprogenitorsand apoptosis of bone marrow cells. The aim of our study was to investigatewhether humoral factors may induce suppression of haematopoiesis by increased apoptosis of CD34 cells. For this purpose, we incubated allogeneic CD34 -enriched cells with sera of 18 leukopenic SLE patients. Apoptosis was induced by four of 18 sera. This effect was independentof complement-inhibitionand FAS-blockade. Although reduced proliferationof autologouspluripotentbone marrow progenitorshas been attributed to an IgG serum inhibitor, removal of IgG from these four proapoptoticsera had no effect on apoptosis of allogeneic CD34 cells. The proapoptotic effect was associated with high titres of anti-dsDNA antibodies and low haemoglobin concentrations, but not with high titres of antinuclear antibodies, TNF-a and IFN-a of the sera tested.

Key Words: apoptosis • immunoglobulin-independent • leukopenia • stem cells • systemic lupus erythematosus

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