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Antigen-specificity of oligoclonal abnormal protein bands in multiple myeloma after allogeneic stem cell transplantation

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Abstract

Myeloma patients may develop oligoclonal immunoglobulins, so-called abnormal protein bands (APB), after stem cell transplantation. APB do not correspond to the patient’s paraprotein and confer a good prognosis. We set out to investigate whether such APB represent a humoral anti-myeloma immune response by screening immunoglobulins of 15 myeloma patients after allogeneic stem cell transplantation and a control group of healthy donors for reactivity with myeloma protein extracts. While the immunoglobulins of healthy donors did not react with myeloma protein extracts, patient-derived immunoglobulins showed variable levels of interaction, depending on the presence of APB on immunofixation. Most commonly, we detected interactions with heat-shock proteins, followed by neutral alpha-glucosidase, alpha-enolase and vimentin, as well as proliferating cell nuclear antigen and MAGEA4. More than 80% of targets were upregulated in myeloma. Heat-shock protein 60 (HSP60) was subsequently evaluated as an exemplary antigen. We found that HSP60 was aberrantly displayed on the surface of primary myeloma cells. Indeed, patient-derived APB-containing immunoglobulins recognized surface HSP60 suggesting that this antigen becomes accessible to the immune system after aberrant membrane exposition. We conclude that immunoglobulin fractions with APB recognize recurrent myeloma antigens and that this humoral response may contribute to the more favorable prognosis in patients with APB.

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Acknowledgments

We thank Martin Trepel for helpful comments and Victoria Martens and Lisa Schindler for technical support. This work was supported by the Wilhelm Sander-Stiftung (grant #2009.035.1 to M.B.) and the Hamburger Krebsgesellschaft (scholarship to M.B.).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Oncology and Hematology, BMT with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumorzentrum, Martinistrasse 52, 20246, Hamburg, Germany

    Janina Rahlff & Mascha Binder

  2. Department of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Maria Trusch, Andrea Horst & Hartmut Schlüter

  3. Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Friedrich Haag

  4. Department for Stem Cell Transplantation, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumorzentrum, Hamburg, Germany

    Ulrike Bacher

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  1. Janina Rahlff
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  2. Maria Trusch
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  3. Friedrich Haag
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  4. Ulrike Bacher
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  7. Mascha Binder
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Correspondence to Mascha Binder.

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Rahlff, J., Trusch, M., Haag, F. et al. Antigen-specificity of oligoclonal abnormal protein bands in multiple myeloma after allogeneic stem cell transplantation. Cancer Immunol Immunother 61, 1639–1651 (2012). https://doi.org/10.1007/s00262-012-1220-x

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  • DOI: https://doi.org/10.1007/s00262-012-1220-x

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