Microchimerism and Autoimmune Disease

Jl, Nelson

doi:10.1056/nejm199804233381711

Cited by 87 publications

(44 citation statements)

References 9 publications

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“…Scleroderma patients could also have quantitative differences of maternal microchimerism from normal subjects that would not be reflected in the current studies, because the HLAspecific assay is not quantitative. That maternal microchimerism could play a role in some systemic autoimmune diseases is supported by experimental models; for example, the introduction of parental cells into F1 progeny is a well-recognized model of systemic lupus erythematosus (29)(30)(31)(32). Homing properties of chimeric cells could be important, as recently suggested by Aractangi et al (33), who found fetal DNA in skin lesions of women with polymorphic eruptions of pregnancy, a skin disorder of pregnancy.…”

Section: Discussionmentioning

confidence: 93%

Microchimerism of maternal origin persists into adult life

Maloney¹,

Smith²,

Fürst³

et al. 1999

J. Clin. Invest.

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411

302

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Section: Discussionmentioning

confidence: 93%

Microchimerism of maternal origin persists into adult life

Maloney¹,

Smith²,

Fürst³

et al. 1999

J. Clin. Invest.

Self Cite

411

302

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“…Among those that have been examined for their roles in the amelioration of rheumatoid arthritis symptoms are the presence of fetal cells in maternal circulation (microchimerism) (40), the presentation of fetal peptides derived from HLA molecules by maternal HLA molecules (41), and increases in levels of steroid hormones, including cortisol, progesterone, and estrogen (29). Estrogen has received considerable attention and has been shown to be effective in down-regulating autoimmunity in a number of autoimmune models (6,7).…”

Section: Figurementioning

confidence: 99%

Estradiol Treatment Redirects the Isotype of the Autoantibody Response and Prevents the Development of Autoimmune Arthritis

Latham

Zamora²,

Drought³

et al. 2003

The Journal of Immunology

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A number of clinical and experimental observations have been made relating elevated estrogen levels with the amelioration of autoimmune diseases, yet questions remain about the levels required for efficacy as well as the mechanism of disease inhibition. Using the collagen-induced arthritis (CIA) model, we have studied the effects of physiological, sustained levels of 17β-estradiol in preventing the development of autoimmune arthritis and analyzed the changes in the autoimmune response. Using time-release pellets of 17β-estradiol, arthritis development was significantly inhibited in three different strains of CIA-susceptible mice compared with the effect of placebo treatment, and serum estradiol levels similar to those of mice in estrus were found to be equally effective as higher estradiol concentrations. Analysis of the autoimmune response in the estradiol-treated mice indicated that T cell production of IFN-γ was markedly decreased, and significant decreases were also observed in levels of IL-10 and GM-CSF produced by lymph nodes cells from estradiol-treated mice. Although the total IgG anti-CII response was only minimally affected by estrogen treatment, a significant reduction in the levels of IgG2a anti-CII Abs and an increase in the levels of IgG1 anti-CII Abs were observed in estradiol-treated mice. These data indicate that estradiol treatment altered the Th profile of the autoimmune T cell response, which, in turn, altered the production of IgG Abs to an isotype that is poor at fixing complement, an important component in the immunopathogenesis of CIA.

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“…While it seems unlikely that human SLE is initiated by recognition of MHC alloantigens as in the GVHD model, the idea cannot be totally excluded in view of reports of persistent maternal-fetal microchimerism in patients with humoral autoimmunity (35). One possibility is that a B-cell tropic virus, such as Epstein-Barr virus, that infects B cells regardless of the antigenic specificity through the complement receptor, CD21 (36), activates an oligoclonal population of viral specific CD4 + and CD8 + T cells.…”

Section: Figurementioning

confidence: 99%

Role of perforin in controlling B-cell hyperactivity and humoral autoimmunity

Shustov¹,

Luzina²,

Nguyen³

et al. 2000

J. Clin. Invest.

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To determine the role of perforin-mediated cytotoxic T lymphocyte (CTL) effector function in immune regulation, we studied a well-characterized mouse model of graft-versus-host disease (GVHD). Induction of acute GVHD using perforin-deficient donor T cells (pfp→F1) initially resulted in features of acute GVHD, e.g., engraftment of both donor CD4 + and CD8 + T cells, upregulation of Fas and FasL, production of antihost CTL, and secretion of both Th1 and Th2 cytokines. Despite fully functional FasL activity, pfp donor cells failed to totally eliminate host B cells, and, by 4 weeks of disease, cytokine production in pfp→F1 mice had polarized to a Th2 response. Pfp→F1 mice eventually developed features of chronic GVHD, such as increased numbers of B cells, persistence of donor CD4 T cells, autoantibody production, and lupuslike renal disease. We conclude that in the setting of B-and T-cell activation, perforin plays an important immunoregulatory role in the prevention of humoral autoimmunity through the elimination of both autoreactive B cells and ag-specific T cells. Moreover, an ineffective initial CTL response can evolve into a persistent antibody-mediated response and, with it, the potential for sustained humoral autoimmunity.This article may have been published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org. J. Clin.

show abstract

Microchimerism and Autoimmune Disease

Cited by 87 publications

References 9 publications

Microchimerism of maternal origin persists into adult life

Microchimerism of maternal origin persists into adult life

Estradiol Treatment Redirects the Isotype of the Autoantibody Response and Prevents the Development of Autoimmune Arthritis

Role of perforin in controlling B-cell hyperactivity and humoral autoimmunity

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