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Journal ArticleDOI

Immunologic and viral factors in the pathogenesis of systemic lupus erythematosus.

01 Nov 1970-Arthritis & Rheumatism (John Wiley & Sons, Inc.)-Vol. 13, Iss: 6, pp 887-894
About: This article is published in Arthritis & Rheumatism.The article was published on 1970-11-01. It has received 120 citations till now. The article focuses on the topics: Anti-SSA/Ro autoantibodies.
Citations
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Journal ArticleDOI
TL;DR: The detection of antibody to ENA with a well defined specificity allows recognition of an apparently distinct mixed connective tissue disease syndrome which is characterized by an excellent response to corticosteroid therapy and a favorable prognosis.

1,632 citations

Book ChapterDOI
TL;DR: This chapter reviews the histopathologic, serologic, lymphocytic, virological, hormonal, and genetic characteristics of murine models of systemic lupus erythematosus (SLE) to 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.
Abstract: 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.

1,487 citations

Journal ArticleDOI
TL;DR: Mice receiving androgen showed improved survival, reduced anti-nucleic acid antibodies, or less evidence of glomerulonephritis as determined by light, immunofluorescent, and electron microscopy, while opposite effects were observed in castrated mice receiving estrogen.
Abstract: NZB/NZW F1 mice of both sexes were castrated at 2 wk of age and implanted subcutaneously with silastic tubes containing either 5-alpha-dihydrotestosterone or estradiol-17-beta. Mice receiving androgen showed improved survival, reduced anti-nucleic acid antibodies, or less evidence of glomerulonephritis as determined by light, immunofluorescent, and electron microscopy. By contrast, opposite effects were observed in castrated mice receiving estrogen. Intact male NZB/NZW F1 mice received androgen implants at 8 mo, an age when they develop an accelerated autoimmune disease associated with a decline in serum testosterone concentration. Such treated mice had improved survival and reduced concentrations of antibodies to DNA and to polyadenylic acid (Poly A). Prepubertal castration of male NZB/NZW F1 mice results in an earlier appearance of IgG antibodies to Poly A. This effect of castration was prevented if neonatal thymectomy was also performed.

596 citations


Cites background from "Immunologic and viral factors in th..."

  • ...Genetic (2), immunologic (3), and viral (4) factors are involved in pathogenesis....

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Book ChapterDOI
TL;DR: This chapter summarizes the data presented in two reviews of experimental acute and chronic immune complex disease produced by nonliving antigens and discusses in detail more recent studies.
Abstract: Publisher Summary No experimental model has provided greater insight into the mechanism of immune complex disease than the experimental serum sickness. The morphological, immunohistological, and serological features of the laboratory models have provided a basis for understanding the pathogenic mechanisms responsible for human glomerulonephritis, vasculitis, and a variety of systemic connective tissue diseases. The subject of experimental acute and chronic immune complex disease produced by nonliving antigens has received extensive review in this series. This chapter summarizes the data presented in these two reviews and discusses in detail more recent studies. Experiments to study acute immune complex disease (serum sickness) have been performed in rabbits almost exclusively. Experimental chronic immune complex disease has proved to be a most useful model in understanding human glomerulonephritis. When injected daily with heterologous serum protein antigens, rabbits with strong antibody responses develop chronic membranous glomerulonephritis in about 5 weeks.

539 citations

Journal Article
TL;DR: In Sjogren's syndrome, as in these other conditions, it seems likely that a combination of genetic, immunologic, and viral or other unknown environmental factors plays a role in pathogenesis.
Abstract: Clinical and pathological evidence suggests that a wide spectrum of lymphoproliferation exists in Sjogren's syndrome (SS), from benign disease with lymphoid infiltrates confined to glandular tissue on the one end, to widespread lymphoreticular malignancy on the other. In the middle of the spectrum are patients threatened by extraglandular extension of lymphoproliferation which is not clinically or histologically malignant and which apparently has the potential to regress with appropriate therapy or to progress to frank neoplasia. Illustrative patients are described. Over thirty other case reports associating SS with pseudolymphoma, Waldenstrom's macroglobulinaemia, reticulum cell sarcoma, or other lymphomas appear in the literature. Similar lymphoproliferative processes have been observed in other autoimmune diseases, in certain immune deficiency states, with hydantoin and other anticonvulsant drugs, and in experimental animal models. In SS, as in these other conditions, it seems likely that a combination of genetic, immunologic, and viral or other unknown environmental factors plays a role in pathogenesis.

321 citations

References
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Journal ArticleDOI
25 Apr 1970-Nature
TL;DR: Preparations of many different types of viruses contain defective particles which consist of viral structural proteins and a part of the viral genome and may play a major part in the evolution of viral diseases.
Abstract: Preparations of many different types of viruses contain defective particles which consist of viral structural proteins and a part of the viral genome. Such particles are capable of specifically interfering with the growth of homologous, standard virus and may play a major part in the evolution of viral diseases.

646 citations

Book ChapterDOI
TL;DR: This chapter discusses the New Zealand Black (NZB) strain of mice that has attracted the attention of investigators throughout the world as an experimental model for human connective tissue disease and describes the patterns of development of the disease processes in the two groups of mice.
Abstract: Publisher Summary This chapter discusses the New Zealand Black (NZB) strain of mice that has attracted the attention of investigators throughout the world as an experimental model for human connective tissue disease. The mice developed an autoimmune type of hemolytic anemia with autoantibody production, and they were the first documented strain of experimental animals to develop autoimmune disease spontaneously. The autoimmune phenomena of the NZB strain appeared in all F 1 hybrids. In some of the hybrid strains, the autoimmune disorder maintained the NZB characteristic of erythrocyte autoantibody production. But in certain others, the nature of the process changed to one of antinuclear antibody production and renal disease in a form closely resembling lupus nephritis. The chapter describes the patterns of development of the disease processes in the two groups of mice. The NZB X NZW hybrid strain with its hybrid vigor, its clear-cut laboratory markers, and its accurately predictable pattern of disease, is a much more satisfactory model. The two groups of animals represent two rather different types of autoimmune disorder. Disorders could be transmitted by isogenic grafts of immunologically competent cells from the spleen, thus identifying such cells as the executive clones responsible for autoantibody production.

582 citations

Journal ArticleDOI
TL;DR: Enhancement of the antinuclear antibody response by active immunization of young NZB/W mice with DNA-methylated BSA hastens the development and increases the severity of the glomerulonephritis.
Abstract: The development of glomerulonephritis in NZB/W mice is closely related to the formation of antinuclear, particularly anti-DNA, antibodies. The developing inflammatory glomerular lesions are characterized by the deposition of gammaG- and beta(1C)-globulins plus DNA and possibly other nuclear antigens, presumably as complexes, in a granular to lumpy pattern along the capillary walls and in the mesangia. Elution studies revealed the gammaG-globulin in the glomeruli to be largely gammaG(2A)-type antibody to soluble nuclear antigens. Enhancement of the antinuclear antibody response by active immunization of young NZB/W mice with DNA-methylated BSA hastens the development and increases the severity of the glomerulonephritis. Similarly, injections of soluble DNA into NZB/W mice with circulating anti-DNA antibodies but with as yet little nephritis causes rapid progression of nephritis.

517 citations

Journal ArticleDOI
TL;DR: The hypothesis is presented that in Sjogren's syndrome the chronic state of immunologic hyperactivity and the proliferation of immunologically competent cells producing abnormal tissue antibodies predispose to the relatively frequent development of malignant lymphoma.

479 citations

Journal ArticleDOI
TL;DR: The transfer of anti-LCM antibody to SWR/J carrier mice results in acute necrotizing inflammatory lesions in regions of viral persistence, followed by chronic mononuclear infiltrates quite similar to those seen after the transfer of immune cells.
Abstract: Mice infected shortly after birth with lymphocytic choriomeningitis (LCM) virus are not immunologically tolerant, although they carry the virus throughout life. These LCM carrier mice make anti-LCM antibody, which apparently complexes with viral antigen in the circulation and these complexes accumulate in the glomeruli. LCM carrier mice of different strains vary significantly as to concentration of detectable infectious virus in their tissue, amount and time of appearance of anti-LCM antibody, and development of an associated chronic disease. The chronic disease consists primarily of glomerulonephritis, focal hepatic necrosis, and disseminated lymphoid infiltrations. LCM carriers of the SWR/J strain contain high tissue concentrations of virus, considerable anti-LCM antibody detectable in the glomeruli by 3 wk to 2 months of age and develop chronic disease within the first 2–3 months of life. In contrast, C3H strain LCM carriers contain 1/1000 as much infectious virus, less detectable anti-LCM antibody, and have not, over a 24 month observation period, developed any detectable disease. B10D2 old and new carrier mice with intermediate amounts of virus develop chronic disease during the latter half of the first year of life. The pathogenesis of the glomerulonephritis of chronic LCM disease is apparently related to the formation of circulating virus-antibody complexes which are trapped in the glomerular filter. There is no evidence for direct glomerular injury by the virus nor for any autoimmune response by the host.

258 citations