Apoptosis and nucleosomes

Drs Berden and Koutouzov presented evidence that nucleosomes are antigens in lupus pathogenesis and that apoptotic cells are the source of nucleosomes. Berden's group measured persistence of circulating nucleosomes and nucleosome–antibody complexes in autoimmune mice and demonstrated nucleosoma...

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Bibliographic Details
Published in:Lupus 2002-01, Vol.11 (12), p.787-789
Main Authors: Stollar, B D, Stephenson, F
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antigens
Apoptosis
Apoptosis - immunology
Autoantigens - immunology
Biochemistry
Diabetes
Diabetic nephropathy
Heparan sulfate
Humans
Immunology
Kidney diseases
Lupus
Lupus Nephritis - immunology
Lupus Nephritis - pathology
Medical research
Nucleosomes - immunology
Pathogenesis
Skin
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Summary:Drs Berden and Koutouzov presented evidence that nucleosomes are antigens in lupus pathogenesis and that apoptotic cells are the source of nucleosomes. Berden's group measured persistence of circulating nucleosomes and nucleosome–antibody complexes in autoimmune mice and demonstrated nucleosomaldepositionin skin of SLE patientsas well as in renal lesions. Koutouzovreported that anti-nucleosomes are among the earliest autoantibodies in MRL‡/‡ mice, appearing several weeks before anti-DNA antibodies. Treatment of the mice with a pro-apoptotic drug, taxote ‘re, accelerated autoantibodyproductionand developmentof lesions. Herrmann proposed that persistent immunization results from reduced dead cell clearance and reduced production of immunosuppressive cytokines by defective scavenger macrophages. He also described accumulation of apoptotic cells in germinal follicles in SLE patients and attachment of nuclear antigens that are produced in apoptosis to the surface of follicular dendritic cells. Apoptosis-derived nucleosomes may be important in both the immunizing and effector arms of pathogenesis.
ISSN:0961-2033
1477-0962
DOI:10.1191/0961203302lu318oa