Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calreticulin is a new human rheumatic disease-associated autoantigen that plays a multifaceted role in cell biology. In earlier studies, this protein was shown to share an intimate relationship with the Ro/SS-A autoantigen complex, although the nature of this association continues to be debated. Since modulation of the Ro/SS-A autoantigen in epidermal keratinocytes has been implicated in the pathogenesis of subacute cutaneous lupus erythematosus and neonatal lupus erythematosus, we have begun to examine the transcriptional regulation of calreticulin. A 504 bp calreticulin promoter fragment was subcloned into a reporter gene plasmid containing firefly luciferase. Calcium ionophore, heat shock, and heavy metals such as zinc and cadmium were consistently found to increase calreticulin transcriptional activities in A431 cells (a human epidermoid squamous carcinoma cell line) under transient transfection conditions. These studies suggest that (a) calreticulin is regulated at the transcriptional level, and (b) calreticulin, like some other LE-related autoantigens, appears to function as a heat shock/stress-response gene.
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PMID:Calreticulin is transcriptionally upregulated by heat shock, calcium and heavy metals. 867 89

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.
Lupus 1997
PMID:Clinical relevance of calreticulin in systemic lupus erythematosus. 930 59

Calreticulin (CR) is widely recognized as a new human autoantigen but there are conflicting data concerning its relationship with the Ro(SS-A) ribonucleoprotein (RNP). Recent evidence suggests that CR binds to 52 kDaRo (Ro52) by a protein/protein interaction and binds to hY RNA and rubella virus RNA. Other studies have shown that initiation of immunity to either Ro52 or 60 kDaRo (Ro60) can lead to reciprocal spreading of autoimmunity to Ro60 or Ro52, respectively, and induce anti-La autoantibodies in some strains of mice. These findings support a physical association of these polypeptides in Ro/La complexes. To test the hypothesis that CR is physically associated with Ro52 and/or Ro60 we examined the sera of Ro52-, Ro60- and La-immunized mice for intermolecular spreading to CR. Immune sera from BALB/c and C3H/HeJ mice immunized with recombinant 6xHis-mouse Ro52, 6xHis-human Ro60 or 6xHis-human La were tested for reactivity by ELISA and immunoblotting with a full-length human CR protein expressed as a soluble maltose binding protein fusion protein (CR-MBP). Five of the six Ro52-immunized C3H/HeJ mice sera and all six Ro60-immunized C3H/HeJ mice sera reacted with the CR-MBP (but not a MBP control) on ELISA. In the BALB/c group, the responder rate was lower with one in six of the Ro52-immunized and one in five of the Ro60-immunized mice spreading to CR. In contrast, none of the BALB/c or C3H/HeJ mice which was immunized with La showed evidence of a recruited anti-CR antibody response. Immunoblotting of the different recombinant proteins with immune sera from the C3H/HeJ mice confirmed the specificity of the initial and recruited antibody responses. The spreading of immunity from Ro52 and Ro60 to CR in Ro-immunized mice suggests that a subpopulation of CR or CR-like molecules must associate under certain circumstances with Ro52 and Ro60 polypeptides in vivo, possibly as Ro/CR complexes concentrated in surface membrane blebs of apoptotic cells. The lack of spreading to CR in La-immunized mice suggests that CR may be associated with a subpopulation of Ro particles from which La has already dissociated.
Lupus 1998
PMID:Spreading of the immune response from 52 kDaRo and 60 kDaRo to calreticulin in experimental autoimmunity. 949 42

Calreticulin (CR) is a new rheumatic disease-associated autoantigen that is intimately associated with the Ro/SS-A ribonucleoprotein. CR autoantibodies are frequently observed in patients with photosensitive forms of lupus erythematosus (LE). CR has been shown to be highly homologous to cC1q-R, the cell surface receptor that binds the collagenous domain of the first component of complement, C1q. C1q has also been shown to directly bind to CR. We therefore asked whether the binding of C1q to CR might interfere with the binding of CR autoantibody to CR. Full-length recombinant human CR, an E. coli fusion proteins was used as antigen in a direct enzyme-linked immunosorbent assay (ELISA). CR autoantibody-containing sera were assayed before and after C1q removal by two different methods: by heating sera at 56 degrees C for 30 min or adding monoclonal anti-C1q antibodies. ELISA optical density (OD) values were found to be consistently higher in sera depleted of C1q by both methods compared to unmodified sera. The addition of purified C1q to C1q-depleted sera resulted in ELISA OD values similar to those of unmodified sera. These results suggest that C1q levels present in human serum can inhibit the binding of CR autoantibody to CR. One can speculate that the failure of C1q to mask CR autoepitopes in individuals with genetic deficiency of C1q could contribute to the high rate of photosensitive LE that occurs in such individuals.
Lupus 1999
PMID:C1q inhibits autoantibody binding to calreticulin. 1041 9