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Few human autoimmune sera detect GPI

Nature Immunology volume 3, pages 411–412 (2002)Cite this article

RA is a common disease with a complex etiology and pathogenesis. Many different animal models are used to study RA. With the use of one such model of a spontaneously developing arthritis, serum antibodies and transgenic T cells were shown to react with the ubiquitously expressed glycolytic enzyme GPI. Purified anti-GPI, as well as sera from sick mice, transmitted RA into naïve mice, even in the absence of B and T cells3,4. In an article published in Nature Immunology by Schaller et al.5, the authors suggested that GPI might be the autoantigen in human RA as well. They also claimed that GPI could be used to diagnose 64% of the RA cases. In particular, sera from other autoimmune diseases, such as Lyme disease and Sjögren's syndrome, did not react with GPI. Thus, this would represent the first molecular tool for diagnosing RA to this extent.

There are a number of obvious differences between our analysis and the one by Schaller et al. For example, the serum data presented in Fig. 1a of their article were obtained at absorbance values that were beyond the limit of linearity of the instrument. The Jackson Laboratory antibody they used as a secondary reagent to detect anti-GPI IgGs was diluted 1:1,000. For us, a dilution of at least 1:10,000 was necessary to lower the background from the healthy donor's sera. We also observed a high background when we used purified rabbit GPI in immunoblots and believe this reagent is not particularly suitable for the detection of human anti-GPI. This is why we used recombinant human GPI (Web Fig. 2 online)—which was HPLC-purified to avoid possible contamination with bacterial products that react with human sera—in our study. We cannot rule out, however, that our patient pool differed genetically (our pool consisted exclusively of Caucasians) or because of environmental factors (diet, for example) from those used by Schaller et al.5 or the possibility that this contributed to the differing data. Clearly though, GPI cannot be used to diagnose or discriminate between any of the autoimmune diseases analyzed because of the low frequency of positives found in several disease groups.

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Figure 1: ELISA detects anti-GPI in 32/462 sera.

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Authors and Affiliations

  1. Department of Biology, Immunology, University of Konstanz, Faculty of Sciences, Immunology, M662, Konstanz, D-78457, Germany

    Daniela Kassahn, Cornelia Kolb, Samuel Solomon, Petra Bochtler & Harald Illges

  2. Biotechnology Institute Thurgau, Konstanzerstr. 19, Tägerwilen, CH-8274, Switzerland

    Harald Illges

Authors
  1. Daniela Kassahn
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  2. Cornelia Kolb
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  3. Samuel Solomon
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  4. Petra Bochtler
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  5. Harald Illges
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Additional information

Note: Supplementary information is available on the Nature Immunology website.

Supplementary information

Web Figure 1.

Rabbit GPI (Sigma) and lysates of the human monocyte cell line HL60 were separated on SDS-PAGE (alternating lanes 1-20), blotted to nitrocellulose membranes and incubated with either 1/50 dilutions of human sera, or with 1/1000 diluted sick K/BxN mouse serum that served as a positive, cross-reacting control. RA sera 1 and 2 and healthy donor (HD) sera 1-3 were negative, RA sera 3-6 showed above background signals by ELISA. For further details see Web Methods online. (JPG 9 kb)

Web Figure 2.

Purification of hGPI. Recombinant human GPI-GST fusion protein was cleaved with thrombin after affinity chromatography on glutathione–sepharose and purified by HPLC. Proteins were separated on SDS PAGE and stained with coomassie blue. Lane 1: low molecular weight marker (Pharmacia, Freiburg, Germany); lane 2: hGPI after thrombin cleavage; lane 3: HPLC purified hGPI. (JPG 30 kb)

Web Methods. (PDF 24 kb)

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Kassahn, D., Kolb, C., Solomon, S. et al. Few human autoimmune sera detect GPI. Nat Immunol 3, 411–412 (2002). https://doi.org/10.1038/ni0502-411b

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