DOI: 10.1097/01.bor.0000174181.93030.59
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PMID: 16093825
Issn Print: 1040-8711
Publication Date: 2005/09/01
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Excerpt
Immune cells from patients who have systemic autoimmune diseases respond to excessively available autoantigen. Immune cells from patients with systemic lupus erythematosus (SLE) have, for still unclear reasons, lost their tolerant status. Conversely, it appears that autoantigen is produced in these patients in increased rates. Addressed in the review by Graham and Utz (pp. 513-517) are the mechanisms that are responsible for the production and availability of autoantigen and how and why certain autoantigens represent prime targets for the autoimmune response. Several antigens appear to undergo post-translational modification during apoptosis, whereas increased granzyme B activity during apoptosis has been shown to be responsible for the production of distinct autoantigens. Viruses have long been implicated in the induction of autoimmunity through the so-called ‘molecular mimicry’ process. Herein the role of viral proteases in the generation of autoantigens is discussed. Interferons appear to elicit the production of autoantigens whereas increased rate of alternative spicing of antigens appears to contribute to the number of available target autoantigens. It is still difficult to understand, however, why only certain autoantigens are selected to serve as a target of the autoimmune response, or conversely, why certain autoantigens elicit an autoimmune response. Studies like those reported by McClain et al. [1] shed light on the order of appearance of the autoimmune response and inferentially point out the antigens that initiate the autoimmune response.
Immune cells from patients with SLE present with distinct biochemical abnormalities. Study of the abnormal biochemical phenotype serves a number of purposes: helping us understand how SLE T cells are different from normal T cells and define whether the SLE T cell represents an otherwise normal cell that has been stimulated or conditioned to express a functional phenotype such as that of an effector or memory T cell. The ability of SLE T cells to display a heightened early cell signaling response is reminiscent of that of an in-vitro generated effector cell, with the distinct difference that although the normal effector T cells produce sufficient amounts of interleukin-2, SLE T cells do not produce interleukin-2 [2].
Kyttaris et al. in this issue (pp. 518-522) review some of the most recently added biochemical defects observed in patients with SLE and in particular how anti-CD3/T-cell receptor antibodies present in the sera of patients with SLE trigger the suppression of the transcription of the interleukin-2 gene. Lack of sufficient amounts of interleukin-2 is apparently responsible for decreased cytotoxic responses against cells infected with the Epstein-Barr virus [3] and the excessive frequency of Epstein-Barr virus-loaded cells in the peripheral blood [4]. It is interesting, however, that SLE sera fail to reproduce in normal cells a number of biochemical aberrations observed in SLE T cells, such as increased calcium responses and decreased T-cell receptor ζ chain expression. Another interesting aspect of SLE sera-mediated immune cell abnormalities is the report that DNA-containing immune complexes stimulate dendritic cells through Toll-like receptor 9 [5].
We have learned much in recent years about the contribution of genes in the expression of autoimmunity in both humans and mice. Bagavant and Fu (pp. 523-528) discuss recent evidence supporting the role of susceptibility genes for end-organ damage and autoreactive T cells in determining disease outcome. The authors note the complex interactions between innate and adaptive immunity resulting in end-organ damage.
Also in this issue, Croker and Kimberly (pp.
