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Research Article Free access | 10.1172/JCI2749

A novel epitope on the C-terminus of SmD1 is recognized by the majority of sera from patients with systemic lupus erythematosus.

G Riemekasten, J Marell, G Trebeljahr, R Klein, G Hausdorf, T Häupl, J Schneider-Mergener, G R Burmester, and F Hiepe

Department of Medicine, Rheumatology and Clinical Immunology, Institute of Medical Immunology, Charitié University Hospital, Humboldt University at Berlin, D-10177 Berlin, Germany.

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Department of Medicine, Rheumatology and Clinical Immunology, Institute of Medical Immunology, Charitié University Hospital, Humboldt University at Berlin, D-10177 Berlin, Germany.

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Department of Medicine, Rheumatology and Clinical Immunology, Institute of Medical Immunology, Charitié University Hospital, Humboldt University at Berlin, D-10177 Berlin, Germany.

Find articles by Trebeljahr, G. in: PubMed | Google Scholar

Department of Medicine, Rheumatology and Clinical Immunology, Institute of Medical Immunology, Charitié University Hospital, Humboldt University at Berlin, D-10177 Berlin, Germany.

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Department of Medicine, Rheumatology and Clinical Immunology, Institute of Medical Immunology, Charitié University Hospital, Humboldt University at Berlin, D-10177 Berlin, Germany.

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Department of Medicine, Rheumatology and Clinical Immunology, Institute of Medical Immunology, Charitié University Hospital, Humboldt University at Berlin, D-10177 Berlin, Germany.

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Department of Medicine, Rheumatology and Clinical Immunology, Institute of Medical Immunology, Charitié University Hospital, Humboldt University at Berlin, D-10177 Berlin, Germany.

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Department of Medicine, Rheumatology and Clinical Immunology, Institute of Medical Immunology, Charitié University Hospital, Humboldt University at Berlin, D-10177 Berlin, Germany.

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Department of Medicine, Rheumatology and Clinical Immunology, Institute of Medical Immunology, Charitié University Hospital, Humboldt University at Berlin, D-10177 Berlin, Germany.

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Published August 15, 1998 - More info

Published in Volume 102, Issue 4 on August 15, 1998
J Clin Invest. 1998;102(4):754–763. https://doi.org/10.1172/JCI2749.
© 1998 The American Society for Clinical Investigation
Published August 15, 1998 - Version history
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Abstract

The SmD1 protein is a specific target for the autoantibody response in SLE. To further analyze this reactivity epitope, mapping was performed with cellulose-bound 13-mer peptides overlapping 10 amino acids (aa). In this initial approach, 4 out of 15 SLE sera recognized more than five overlapping peptides of the SmD1 C-terminus. Therefore, longer oligopeptides of up to 37 aa of this region were generated and probed for as antigens by ELISA. For the SmD1 aa 83-119 polypeptide, there was a striking increase of reactivity with 70.0% positive reactions out of 167 SLE sera. In contrast, 105 healthy control sera were negative, and only 8.3% of sera from patients with other inflammatory diseases (n = 267) exhibited a response, which was of low level only. The anti-SmD183-119 reactivity was significantly higher in anti-dsDNA antibody positive vs. negative sera (P < 0.001) and correlated with disease activity. Four of five human monoclonal anti-dsDNA antibodies also reacted with SmD183-119. The specificity for SmD1 was demonstrated by inhibition experiments and immunization of rabbits with SmD183-119 inducing SmD1-specific antibodies. In conclusion, the SmD183-119 peptide was demonstrated to be an important and highly specific target of the autoimmune response in SLE. The high sensitivity of this ELISA probably depends on a conformational epitope, which appears not to be accessible in the full-size SmD1 protein.

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