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Systemic Lupus Erythematosus
- Alfred D. Steinberg, MD;
- Mark F. Gourley, MD;
- Dennis M. Klinman, MD, PhD;
- George C. Tsokos, MD;
- Dorothy E. Scott, MD; and
- Arthur M. Krieg, MD
Abstract
▪ Although the cause of systemic lupus erythematosus remains unknown, pathogenic mechanisms are becoming clearer. Both genetic and environmental factors have been implicated in the induction and in the perpetuation of lupus. Implicated environmental triggers include ultraviolet light, chemicals (hydrazines, hair dyes, drugs), some foods, and possibly infectious agents.
Lupus is mediated by the immune system. Patients have excess numbers of antibody-forming cells, including those that produce antibodies reactive with self-antigens. Patients also have an increased number of activated T cells, some of which help B cells to produce autoantibodies. A loss of tolerance is a critical immune abnormality in lupus; many of the activated helper T cells may result from a failure in normal tolerance mechanisms. A hematopoietic stem-cell defect could give rise to both B- and T-cell abnormalities. Such a stem-cell abnormality might lead to both a loss of self-tolerance and polyclonal B-cell activation. Antigen-driven, T-cell-dependent expansion of B-cell clones would then give rise to pathogenic autoantibodies, including anti-DNA. We believe that lupus is a syndrome: Patients differ regarding specific inciting factors and immune defects. Some patients have genetically conditioned abnormalities, similar to those found in mice with lupus; others have a combination of genetic and acquired defects. We hope that insights into pathogenesis lead to improved and more individualized therapy.
Article and Author Information
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An edited summary of a Combined Clinical Staff Conference held 27 February 1991 at the Amphitheater, Building 10, Bethesda, Maryland. The conference was sponsored by the National Institutes of Health, U.S. Department of Health and Human Services.
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Authors who wish to cite a section of the conference and specifically indicate its author may use this example for the form of the reference:
Klinman DM. B cells, pp 550-552. In: Steinberg AD, moderator. Systemic lupus erythematosus. Ann Intern Med. 1991;115:548-559.
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Grant Support: Dr. Krieg is supported by a fellowship from the Arthritis Foundation.
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Requests for Reprints: Alfred D. Steinberg, MD, Building 10, Room 9N218, National Institutes of Health, Bethesda, MD 20892.
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Current Author Addresses: Dr. Steinberg: Building 10, Room 9N218, National Institutes of Health, Bethesda, MD 20892.
Drs. Gourley and Scott: Building 10, Room 9N216, National Institutes of Health, Bethesda, MD.
Dr. Klinman: Building 29A, Room 3D10, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892.
Dr. Tsokos: Building 10, Room 3N112, National Institutes of Health, Bethesda, MD 20892.
Dr. Krieg: 540 EMRB, University of Iowa, Iowa City, IA 52242.
