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Response to 'Autoantibodies to GPI and creatine kinase in RA' and 'Few human autoimmune sera detect GPI'

Nature Immunology volume 3, pages 412–413 (2002)Cite this article

Based on the demonstration that GPI could serve as an autoantigen for both B and T cells in a TCR-transgenic mouse model of arthritis, and that passive transfer of anti-GPI antibodies to normal healthy animals induced arthritis1, we performed studies on the human autoimmune response to GPI2. Using serology and human antibody cloning by phage display, we found evidence that GPI is also an autoantigen in human RA. Increased anti-GPI IgG titers were present in both the sera and synovial fluids of approximately two-thirds of RA patients, and these antibodies formed immune complexes that precipitated on the synovial lining. In contrast, such antibodies were only found in a few healthy individuals or patients with Lyme arthritis or primary Sjögren's syndrome.

Schubert et al. and Kassahn et al. state that they examined additional cohorts of patients with RA and other arthritic or autoimmune conditions and found GPI antibodies in only a few RA patients. Schubert et al. studied 61 RA sera for binding to either recombinant human GPI expressed as a His tag fusion protein or commercially available GPI purified from rabbits in ELISA assays. They found increased serum titers to the rabbit GPI preparation in only 15/61 RA patients, 1/32 healthy donors and 9/21 patients with other rheumatic diseases. Examination of these sera for reactivity to human recombinant GPI showed that even fewer sera exhibited binding (2/61). Immunoblotting and mass spectrometry analysis showed that the discrepancy in the frequency of GPI-positive serum, which they observed using purified rabbit GPI and recombinant human GPI, was partially caused by reactivity to a contaminating protein (creatine kinase) in the rabbit GPI preparation. Although results of Schubert et al. support the conclusion that the reactivity they observed against the rabbit GPI preparation in four RA patients was against creatine kinase that contaminated the preparation, serum antibody binding to creatine kinase was not responsible for the anti-rabbit GPI reactivity we observed.

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Figure 1: Correlation between serum IgG reactivity to purified rabbit GPI and recombinant human GPI.

References

  1. Matsumoto, I., Staub, A., Benoist, C. & Mathis, D. Science 286, 1732–1735 (1999).

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  2. Schaller, M., Burton, D. R. & Ditzel, H. J. Nature Immunol. 2, 746–753 (2001).

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Authors and Affiliations

  1. Departments of Immunology, IMM2, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, 92037, CA, USA

    Monica Schaller, Vivian M. Benoit & Henrik J. Ditzel

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  1. Monica Schaller
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  2. Vivian M. Benoit
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  3. Henrik J. Ditzel
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Note: Supplementary information is available on the Nature Immunology website.

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Web Figure 1.

Silver-stained gel of human recombinant GPI purified using glutathione sepharose 4B following site-specific protease cleavage of GST-GPI fusion protein with thrombin. The GST-GPI was expressed in Escherichia coli BL21 using the pGEX-4T-1 vector (Amersham). Lane 1: Human recombinant GPI (5 µg), lane 2: Low range silver-stain standard (Biorad). (JPG 6 kb)

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Schaller, M., Benoit, V. & Ditzel, H. Response to 'Autoantibodies to GPI and creatine kinase in RA' and 'Few human autoimmune sera detect GPI'. Nat Immunol 3, 412–413 (2002). https://doi.org/10.1038/ni0502-412

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