Serological cross-reactivity between a human Ro/SS-A autoantigen (calreticulin) and the lambda Ral-1 antigen of Onchocerca volvulus.

Lux, F A; McCauliffe, Daniel P.; Büttner, Dietrich W.; Lucius, Richard; Capra, J D; Sontheimer, R D; Lieu, Tsu-San

doi:10.1172/jci115801

Cited by 27 publications

(11 citation statements)

References 20 publications

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“…ELISA studies revealed that anti-CRT autoantibodies were directed against the N-terminal fragment. This supports the previous studies in which native Wil-2 cell CRT was proteolytically cleaved into a 23-kD N-terminal and 37-kD C-terminal fragment, of which the N-terminal fragment was found to be autoantigenic [27]. Synthetic peptides corresponding to amino acids 7-24 of human CRT have also been found to react specifically with anti-Ro/SS-A sera in ELISA [20].…”

Section: C1q-calreticulin Interaction In Sle 187supporting

confidence: 89%

The systemic lupus erythematosus (SLE) disease autoantigen—calreticulin can inhibit C1q association with immune complexes

Kishore

Sontheimer

Sastry

et al. 1997

Clinical and Experimental Immunology

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SUMMARYFollowing its release from cells during infection and inflammation, calreticulin (CRT) can act as an autoantigen in diseases such as SLE. Why CRT is a target of protective immunity and whether it may interfere with innate immunity once released from cells during inflammation is unclear. In the present study, we found that CRT was detected more frequently in SLE sera and in higher amounts than found in control sera. Approximately 40% of SLE sera tested contained autoantibodies against CRT as detected by ELISA and immunoblotting. CRT was found to be predominantly in the sera of SLE patients associated with immune complexes and C1q, and only bound to the surfaces of neutrophils in the presence of low levels of calcium and magnesium. In order to further investigate the C1q-CRT interaction, recombinant CRT and its discrete domains (N-, P-, and C-domains) were produced in Escherichia coli. CRT binds to globular head region of C1q primarily via its N-and P-domains. The N-domain was shown to be the most autoantigenic region of CRT, as the anti-CRT autoantibodies from most patients reacted against this region. CRT also altered C1q-mediated immune functions. The P-domain of CRT bound to C1q and reduced the binding of immune complexes in SLE sera to immobilized C1q. Full length CRT and its N-and P-domains were able to reduce the C1q-dependent binding of immune complexes to neutrophils and solid-phase bound C1q. We conclude that CRT, once released from leucocytes during inflammation, may not only induce an antigenic reaction, but also interfere with C1q-mediated inflammatory processes.

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Section: C1q-calreticulin Interaction In Sle 187supporting

confidence: 89%

The systemic lupus erythematosus (SLE) disease autoantigen—calreticulin can inhibit C1q association with immune complexes

Kishore

Sontheimer

Sastry

et al. 1997

Clinical and Experimental Immunology

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“…15 In Leishmania and Schistosoma species, the Ca 2+ binding property of CR is conserved in vitro. 16 There also is evidence concerning immunogenicity of CR from parasites in humans; anti-CR antibodies have been detected in serum from patients with onchocercosis, 17 schistosomiasis, 18 and tripanosomiasis. 19 Our results suggest the presence of a CR-like molecule in E. histolytica that appears highly immunogenic in patients with invasive amebiasis.…”

Section: Discussionmentioning

confidence: 99%

Calreticulin-like molecule in trophozoites of Entamoeba histolytica HM1:IMSS (Swissprot: accession P83003).

González¹,

Rico²,

Mendoza³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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In this work, we report the partial sequence of a 51 kDa protein of Entamoeba histolytica that is highly immunogenic in humans. Partial sequencing of the N-terminal end showed that 18 of the first 20 amino acid residues of the protein were identified uniquely, indicating that the final product was a homogeneous protein preparation. The N-terminal sequence that was found was: KVYFEETFENGWKXIWSKW. Comparing the 19-amino acid sequence of the protein in automated databases shows significant similarity with amino acid sequences of the calreticulin-like protein of spinach leaves (77%) and of the calreticulin precursor of Dictyostelium discoideum (60%).

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“…These include the filarial parasite and causative agent of river blindness Onchocerca [52], the blood fluke Schistosoma [53], the malarial parasite Plasmodium [54] and the trypanosome Leishmanania [2]. Two independent groups showed that autoantibody reactivity against the onchocercal calreticulin homologue (RAL-1) was significantly higher in O. volvulus-infected individuals than in endemic controls [55,56], suggesting that autoantibody reactivity against calreticulin and other autoantigens was intercorrelated as part of an onchocerciasis-associated autoimmune response. The recognition of RAL-1 by the host immune system suggests that it may be secreted by the parasite, which is plausible since the protein lacks an ER retention signal.…”

Section: Calreticulin and Protein Homology To Parasitic Proteins And mentioning

confidence: 99%

Pathophysiological Roles of Calreticulin in Autoimmune Disease

Eggleton

Llewellyn

1999

Scand J Immunol

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Eggleton P, Llewellyn DH. Pathophysiological Roles of Calreticulin in Autoimmune Disease. Scand J Immunol 1999;49:466-473 Autoantibodies against the endoplasmic reticulum (ER) luminal protein, calreticulin are often present in sera from patients with systemic lupus erythematosus, rheumatic disease and various parasitic diseases including onchocerciasis. New information has revealed that calreticulin is implicated in a number of autoimmune processes, including molecular mimicry, epitope spreading, complement inactivation and stimulation of inflammatory mediators, such as nitric oxide production. Calreticulin also binds to the Ro/SS-A antigen complex, which is composed of at least three immunologically distinct proteins bound to a group of small cytoplasmic RNAs that together form a common target for autoimmune responses. Up-regulation of calreticulin at the protein and RNA levels can be triggered by cell stresses, including heat shock, exposure to heavy metals and perturbation of normal ER function, which may in some cases lead to its secretion from cells. Calreticulin is targeted by autoantibodies following its release into the extracellular environment, possibly as a result of cell death, or its presence at the cell surface in response to insults such as viral infection or ultraviolet irradiation. These findings suggest that calreticulin is not just an autoantigen, but plays an active role in the pathology of various autoimmune disease through determinant spreading.

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Serological cross-reactivity between a human Ro/SS-A autoantigen (calreticulin) and the lambda Ral-1 antigen of Onchocerca volvulus.

Abstract: We have cloned and sequenced a 46-kD Ro

Cited by 27 publications

References 20 publications

The systemic lupus erythematosus (SLE) disease autoantigen—calreticulin can inhibit C1q association with immune complexes

The systemic lupus erythematosus (SLE) disease autoantigen—calreticulin can inhibit C1q association with immune complexes

Calreticulin-like molecule in trophozoites of Entamoeba histolytica HM1:IMSS (Swissprot: accession P83003).

Pathophysiological Roles of Calreticulin in Autoimmune Disease

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