A radioimmunoassay for ng quantities of DNA was developed. [125l]lododeoxyuridine-labeled DNA was used as the antigen, and the serum of a lupus erythematosus patient served as the source of antibody. The level of free DNA in the serum of 173 patients with various types of cancer and in 55 healthy individuals was determined by this radioimmunoassay. DNA concentration in the normal controls had a range of 0 to 100 ng/ml with a mean of 13 +/- 3 ng/ml (S.E.). For comparison purposes, the range of 0 to 50 ng/ml was designated as normal, and 93% of controls were found in this range. In the cancer patients, the DNA concentration ranged from zero to mug levels with a mean of 180 +/- 38 ng/ml. Fifty % of the patients values were found in the range of 0 to 50 ng/ml; the other 50% were between 50 and 5000 ng/ml. No correlation could be seen between DNA levels and the size or location of the primary tumor. Significantly higher DNA levels, however, were found in the serum of patients with metastatic disease (mean of 209 +/- 39 ng/ml), as compared to nonmetastatic patients (mean 100 +/- 30, p less than 0.02). After radiation therapy in lymphoma, lung, ovary, uterus, and cervical tumors, the levels decreased in 66 to 90% of the patients, whereas in glioma, breast, colon, and rectal tumors, the DNA levels decreased only in 16 to 33% of the patients. Generally, the decrease in DNA concene of tumor size and reduction of pain. Conversely, when DNA levels either increased or remained unchanged, a lack of response to the treatment was noted. Of 17 patients who died within a year, 13 showed DNA levels that remained high or unchanged, whereas only 4 showed lower levels during treatment. Persistent high or increasing DNA levels in the circulation, therefore, may signal a relapse and are probably a poor prognostic sign. The relatively high percentage (50%) of cancer patients with apparently normal DNA levels would suggest that this test may have low diagnostic value. It should be pointed out, however, that all these patients represent a selected group considered for radiation therapy, usually after surgery and/or chemotherapy. It is possible that a better correlation between DNA levels and cancer will be obtained prior to the initiation of treatment. On the other hand, DNA in the serum may be an important tool for the evaluation of therapy or the comparison of different regimens.

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Free DNA in the Serum of Cancer Patients and the Effect of Therapy

Mixed connective tissue disease-an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA)

Biologic and clinical significance of cryoglobulins. A report of 86 cases.

Publisher Summary This chapter reviews the histopathologic, serologic, lymphocytic, virological, hormonal, and genetic characteristics of murine models of systemic lupus erythematosus (SLE). The pathogenetic mechanisms underlying murine SLE are highly complex, apparently well-programmed genetically, but still diverse and their bases not as yet well defined. Significant serologic and cellular experimental data support the statement that the final immunopathologic perturbation in murine (and human) SLE is a B lymphocyte hyperactivity with corresponding enhancement of serum antibodies and autoantibodies, particularly IgG, and consequent formation of pathogenic antigen–antibody ICs. On the basis of the available data, it appears that this B cell hyperactivity is polyclonal but not necessarily panclonal in nature, because not only antibodies against a wide array of autoantigens but also antibodies against incidental antigens, such as haptens, can be detected. The presence of autoantibodies and of their idiotypes in some recombinant lupus x normal murine lines expressing the normal partner's V genes, normal mice in which an exogenous or endogenous (Ipr gene) immunostimulator has been introduced, and unmanipulated normal mice indicate that lupus mice are not unique in their structural genetic Ig elements, whose presence determines the development of their autoimmune disease. The cause of B cell hyperactivity in lupus has not yet been fully elucidated. Autonomous B cell maturation does not appear likely, because B cell proliferation and differentiation in lupus mice was found to be dependent on the same number of accessory signals as in normal mice.

Murine models of systemic lupus erythematosus.

There is more than one interleukin 1.

The natural history of systemic lupus erythematosus by prospective analysis.

Vasculitis with hepatitis B antigenemia: long-term observation in nine patients.

https://www.amjmed.com/article/0002-9343(84)90434-0/pdf

Clinical and microbial features of prosthetic joint infection

Antibodies to measles and parainfluenza type 1 viruses were significantly increased in systemic lupus erythematosus and Reiter's syndrome. Of the individuals with highest titers of measles antibody, 75 percent had neurologic illness. Persistent virus infection may be a factor in the pathogenesis of these diseases.

https://science.sciencemag.org/content/sci/168/3934/982.full.pdf

Myxovirus Antibody Increases in Human Connective Tissue Disease

Six patients with biopsy-proven polyarteritis nodosa and chronic Australia antigenemia are described. Evidence was found in these patients for the presence of circulating immune complexes composed of Australia antigen and immunoglobulin. In addition, in two patients immunofluorescent studies localized Australia antigen, IgM, and complement in the blood vessel walls.

/pdf/vasculitis-in-association-with-australia-antigen-44gd0d9sab.pdf

Charles L. Christian

Papers

The natural history of systemic lupus erythematosus by prospective analysis.

Vasculitis with hepatitis B antigenemia: long-term observation in nine patients.

Clinical and microbial features of prosthetic joint infection

Myxovirus Antibody Increases in Human Connective Tissue Disease

Vasculitis in association with australia antigen.