Clinical relevance of calreticulin in systemic lupus erythematosus.

Department of Biochemistry, University of Oxford, UK.
Lupus (Impact Factor: 2.48). 02/1997; 6(7):564-71. DOI: 10.1177/096120339700600703
Source: PubMed

ABSTRACT Calreticulin is an abundant intracellular protein which is proposed to have numerous biological functions. However, there is increasing evidence to suggest that calreticulin plays a multifunctional role as an autoantigen present in patients with systemic lupus erythematosus. In this review we detail some of the recent evidence which indicate that calreticulin may play a supportive role in the formation of the autoantigen complex-Ro/SS-A. In addition, several proposed mechanisms of release and surface expression of calreticulin are described in relation to SLE mediated responses to the autoantigen. In particular, the generation of autoantibodies to specific regions of the protein and the ability of calreticulin to interfere with complement mediated inflammatory processes.

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    ABSTRACT: Objective Systemic lupus erythematosus (SLE) is an autoimmune disease that affects women nine times more often than men. The present study investigates estradiol-dependent control of the calcium-buffering protein, calreticulin, to gain further insight into the molecular basis of abnormal T cell signaling in SLE T cells.MethodsT cells were purified from blood samples obtained from healthy females and SLE patients. Calreticulin expression was quantified by real-time polymerase chain amplification. Calreticulin and estrogen receptor-α were co-precipitated and analyzed by Western blotting to determine if the proteins associate in T cells.ResultsCalreticulin expression increased (p = 0.034) in activated control T cells, while estradiol decreased (p = 0.044) calreticulin in resting T cells. Calreticulin expression decreased in activated SLE T cell samples and increased in approximately 50% of resting T cell samples. Plasma estradiol was similar (p > 0.05) among SLE patients and control volunteers. Estrogen receptor-α and calreticulin co-precipitated from nuclear and cytoplasmic T cell compartments.Conclusions The results indicate that estradiol tightly regulates calreticulin expression in normal human T cells, and the dynamics are different between activated and resting T cells. The absence of this tight regulation in SLE T cells could contribute to abnormal T cell function.
    Lupus 03/2013; 22(6). DOI:10.1177/0961203313482742 · 2.48 Impact Factor
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    Frontiers in Oncology 01/2015; 5(7). DOI:10.3389/fonc.2015.00007
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    Placenta 08/2013; 34(11). DOI:10.1016/j.placenta.2013.07.068 · 3.29 Impact Factor