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Clinical and serological associations of autoantibodies to GW bodies and a novel cytoplasmic autoantigen GW182

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Abstract

A novel autoantigen named GW182 was recently identified when the serum from a patient with a sensory ataxic polyneuropathy was used to immunoscreen a HeLa cDNA library. Unique features of the GW182 protein include 39 repeats of glycine (G) and tryptophan (W) residues, binding to a subset of messenger RNA and localization to unique structures within the cytoplasm that were designated GW bodies (GWBs). The goal of the present study was to identify the clinical features of patients with anti-GW182 antibodies and to characterize the B cell anti-GW182 response by defining the epitopes bound by human autoantibodies. The most common clinical diagnosis of patients with anti-GW182 antibodies was Sjögren’s syndrome followed by mixed motor/sensory neuropathy, and systemic lupus erythematosus. Of interest, 5 (28%), 9 (50%), and 3 (17%) of the 18 sera that react with GWBs had autoantibodies to the GW182 and the 52 kDa and 60 kDa SS-A/Ro autoantigens, respectively. Epitopes bound by the human autoantibodies were mapped to the GW-rich middle part of the protein, the non-GW rich region, and the C-terminus of GW182 protein. None of the GW182 epitopes had significant sequence similarities to other known proteins. GW182 represents a new category of ribonucleoprotein autoantigens.

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Abbreviations

GWB :

Glycine tryptophan-rich cytoplasmic structure

IIF :

Indirect immunofluorescence

IP :

Immunoprecipitation

NET2 :

NaCl, EDTA, Tris buffer

SDS :

Sodium dodecyl sulfate

SjS :

Sjögren’s syndrome

SLE :

Systemic lupus erythematosus

TBS :

Tris-buffered saline

TnT :

Transcription and translation

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Acknowledgements

We acknowledge the technical assistance of Joan Miller, Cheryl Hanson, Jill Wenger (University of Calgary) and Dr. Zheng Yang (Scripps Research Institute). This work was supported in part by the Canadian Institutes for Health Research Grant MOP-57674 and the National Institutes of Health Grants AR42455, AI47859 and AI39645. M.J.F holds the Arthritis Society Chair at the University of Calgary.

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Authors and Affiliations

  1. Departments of Medicine and Medical Biochemistry, University of Calgary, 3330 Hospital Dr. N.W., Calgary, AB, T2N-4N1, Canada

    Theophany Eystathioy, LeeAnne M. Luft, Douglas W. Zochodne & Marvin J. Fritzler

  2. Department of Oral Biology, University of Florida, Gainesville, Florida, USA

    Edward K. L. Chan

  3. Department of Rheumatology, School of Medicine, Juntendo University, Tokyo, Japan

    Ken Takeuchi

  4. Institute for Molecular Genetics, Universität Heidelberg, Heidelberg, Germany

    Michael Mahler

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  1. Theophany Eystathioy
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  2. Edward K. L. Chan
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  3. Ken Takeuchi
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  4. Michael Mahler
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  7. Marvin J. Fritzler
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Correspondence to Marvin J. Fritzler.

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Eystathioy, T., Chan, E.K.L., Takeuchi, K. et al. Clinical and serological associations of autoantibodies to GW bodies and a novel cytoplasmic autoantigen GW182. J Mol Med 81, 811–818 (2003). https://doi.org/10.1007/s00109-003-0495-y

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  • DOI: https://doi.org/10.1007/s00109-003-0495-y

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