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A Hypothesis of Etiologic Factors in Pathogenesis

Joseph Sonnabend, MB, MRCP; Steven S. Witkin, PhD; David T. Purtilo, MD

JAMA. 1983;249(17):2370-2374.

Abstract
The acquired immunodeficiency syndrome (AIDS) occurs in a subgroup of male homosexuals having sexual contact with a large number of partners. Uncommonly, AIDS has also been diagnosed in Haitians, hemophiliacs, and intravenous drug users and their infants. Manifestations include autoimmune disturbances, opportunistic infections, Kaposi's sarcoma, chronic lymphadenomegaly, non-Hodgkin's lymphoma, or squamous cell carcinoma. The hypothesis receiving most consideration is that a yet-to-be-identified virus causes AIDS. An alternative view is that repeated sexual involvement with multiple partners, in a subgroup of male homosexuals, exposes the men to the immunosuppressive impact of cytomegalovirus (CMV) and allogeneic semen. Antibody to asialo-Gm₁ and other antigens on sperm react with and impair lymphoid cells. We propose a biphasic process. First, a reversible acquisition phase of impaired T-cell immunoregulation permits reactivation of Epstein-Barr virus (EBV), and autoantibodies are produced by the activated B cells. If sexual activity continues at a high level, accumulating immune defects, including destruction of thymic epithelium, lead to a second, self-sustaining phase wherein cytotoxic lymphocytes fail to eliminate herpesvirus-infected cells. Evidence is mounting that Kaposi's sarcoma is caused by CMV and that EBV is responsible for the B-cell lymphomas in these patients. Multiple factors, rather than a novel virus, probably induce AIDS in male homosexuals. If this hypothesis is correct, then rational bases for prevention and intervention can be designed.

(JAMA 1983;249:2370-2374)

Author Affiliations
From the Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Md (Dr Sonnabend); the Department of Obstetrics and Gynecology, Cornell University Medical College, New York (Dr Witkin); and the Department of Pathology and Laboratory Medicine and the Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha (Dr Purtilo).

Footnotes
Reprint requests to Department of Pathology and Laboratory Medicine, University of Nebraska Medical Center, 42nd and Dewey Avenue, Omaha, NE 68105 (Dr Purtilo).

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