Systemic lupus erythematosus is associated with increased auto‐antibody titers against calreticulin and Grp94, but calreticulin is not the Ro/SS‐A antigen

Boehm, J.; Orth, Thomas; Nguyen, Phuc Van; Söling, Hans‐Dieter

doi:10.1111/j.1365-2362.1994.tb01082.x

Cited by 62 publications

(49 citation statements)

References 35 publications

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“…Recently, Rokeach et al [18] and Boehm et al [19] were able to demonstrate that calreticulin is not a Ro/SS-A antigen, but we have shown, on the other hand, that human calreticulin is an autoantigen in patients with systemic lupus erythematosus.…”

Section: Introductioncontrasting

confidence: 63%

Complete congenital heart block is associated with increased autoantibody titers against calreticulin

Orth

Dörner

Büschenfelde

et al. 1996

Eur J Clin Investigation

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Abstract. Complete congenital heart block (CCHB) is associated with anti-Ro/SS-A and anti-La/SS-B antibodies. Calreticulin, a calcium-binding, multifunctional protein of the endoplasmic reticulum with C-terminal KDEL-sequence, is not part of the Ro/SS-A ribonucleoprotein complex. In this study anti-calreticulin autoantibody responses in serum samples from 18 infants with CCHB, their mothers and in a control group of 11 antiRo/SS-A or anti-La/SS-B positive infants without heart block and their mothers were analysed. Specific enzymelinked immunosorbent assays were performed. Nine out of 18 sera with CCHB contained IgG anti-calreticulin antibodies. Four sera of those with IgG antibodies also had IgM antibodies. One serum contained anti-calreticulin IgM antibodies only. In the non-CCHB group two sera were positive for IgG and one serum was positive for IgM anti-calreticulin antibodies. Sera of healthy infants were negative both for anti-IgG and anti-IgM calreticulin antibodies. Calreticulin is involved in calcium storage and therefore anti-calreticulin antibodies might influence the development of CCHB. The new finding of IgM autoantibodies and the observed differences in antibody response in infants and mothers support the hypothesis of a fetally mediated and passively acquired autoimmune disease.

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Section: Introductioncontrasting

confidence: 63%

Complete congenital heart block is associated with increased autoantibody titers against calreticulin

Orth

Dörner

Büschenfelde

et al. 1996

Eur J Clin Investigation

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“…Interestingly, the average level of serum CRT in RA patients was ∼5-fold higher than that of SLE patients (24.31 6 8.97 versus 4.70 6 1.89 ng/ml; p , 0.05). It has previously been reported that SLE is associated with increased anti-CRT Ab titers (28,29). However, by using the rCRT/392-272-based ELISA, we detected CRT-specific IgG Abs in sera from not only the patient groups but also from control subjects, and average levels of such Abs in the three groups were not significantly different (Fig.…”

Section: Detection Of Soluble Crt In Patient Seramentioning

confidence: 77%

Functional Analysis of Recombinant Calreticulin Fragment 39–272: Implications for Immunobiological Activities of Calreticulin in Health and Disease

Cheng

Qiu

et al. 2010

The Journal of Immunology

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Although calreticulin (CRT) is a major Ca2+-binding luminal resident protein, it can also appear on the surface of various types of cells and it functions as an immunopotentiating molecule. However, molecular mechanisms underlying the potent immunobiological activity of cell surface CRT are still unclear. In the present study, a recombinant fragment (rCRT/39–272) covering the lectin-like N domain and partial P domain of murine CRT has been expressed in Escherichia coli. The affinity-purified rCRT/39–272 assembles into homodimers and oligomers in solution and exhibits high binding affinity to various glycans, including carrageenan, alginic acids, and hyaluronic acids. Functionally, rCRT/39–272 is capable of driving the activation and maturation of B cells and cytokine production by macrophages in a TLR-4–dependent manner in vitro. It specifically binds recombinant mouse CD14, but not BAFFR and CD40. It is also able to trigger Ig class switching by B cells in the absence of T cell help both in vitro and in vivo. Furthermore, this fragment of CRT exhibits strong adjuvanticity when conjugated to polysaccharides or expressed as part of a fusion protein. Soluble CRT can be detected in the sera of patients with rheumatoid arthritis or systemic lupus erythematosus, but not in healthy subjects. We argue that CRT, either on the membrane surface of cells or in soluble form, is a potent stimulatory molecule to B cells and macrophages via the TLR-4/CD14 pathway and plays important roles in the pathogenisis of autoimmune diseases.

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“…[47][48][49][50] Interestingly, anti-CRT IgA titers are more useful than anti-CRT IgG levels for detecting mammary, colorectal, hepatocellular and pancreatic carcinomas, alcoholic hepatitis, refractory celiac disease or primary biliary cirrhosis. 30,[51][52][53] High concentrations of anti-CRT IgA antibodies were more frequently detected in lymph node-positive breast cancers than IgG antibodies, but failed to correlate with CRT membrane expression.…”

Section: Discussionmentioning

confidence: 99%

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

et al. 2013

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Immunogenic cell death induced by cytotoxic compounds contributes to the success of selected chemotherapies by eliciting a protective anticancer immune response, which is mediated by CD4 þ and CD8 þ T cells producing interferon-c. In many instances, cancer progression is associated with high titers of tumor-specific antibodies, which become detectable in the serum, but whose functional relevance is elusive. Here, we explored the role of humoral immune responses in the anticancer efficacy of anthracyclines. Chemotherapy reduced the number of tumor-infiltrating B cells, and failed to promote humoral responses against immunodominant tumor antigens. Although anthracycline-based anticancer chemotherapies failed in T cell-deficient mice, they successfully reduced the growth of cancers developing in mice lacking B lymphocytes (due to the injection of a B-celldepleting anti-CD20 antibody), immunoglobulins (Igs) or Ig receptors (Fc receptor) due to genetic manipulations. These results suggest that the humoral arm of antitumor immunity is dispensable for the immune-dependent therapeutic effect of anthracyclines against mouse sarcoma. In addition, we show here that the titers of IgA and IgG antibodies directed against an autoantigen appearing at the cell surface of tumor cells post chemotherapy (calreticulin, CRT) did not significantly increase in patients treated with anthracyclines, and that anti-CRT antibodies had no prognostic or predictive significance. Collectively, our data indicate that humoral anticancer immune responses differ from cellular responses in, thus far, that they do not contribute to the success of anthracycline-mediated anticancer therapies in human breast cancers and mouse sarcomas.

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Systemic lupus erythematosus is associated with increased auto‐antibody titers against calreticulin and Grp94, but calreticulin is not the Ro/SS‐A antigen

Cited by 62 publications

References 35 publications

Complete congenital heart block is associated with increased autoantibody titers against calreticulin

Complete congenital heart block is associated with increased autoantibody titers against calreticulin

Functional Analysis of Recombinant Calreticulin Fragment 39–272: Implications for Immunobiological Activities of Calreticulin in Health and Disease

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines

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