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IgM ANCA in healthy individuals and in patients with ANCA-associated vasculitis

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Abstract

Low levels of IgM auto-antibodies have been reported in health and disease. IgM anti-neutrophil cytoplasmic antibodies (ANCA) have been reported in patients with ANCA-associated vasculitis (AAV). We sought to investigate if healthy individuals may have IgM ANCA in their sera. The first aim of the study was to determine whether IgM ANCA was present in healthy individuals and in patients with ANCA-associated vasculitis. The second aim was to determine what happens to IgM ANCA levels over time. The third aim was to determine whether bacterial infections affected IgM ANCA levels in non-AAV patients. Sera from healthy individuals and patients with AAV were tested for IgM ANCA by immunofluorescence on fixed neutrophils, immunoprecipitation, Western blot and ELISA. Peripheral blood mononuclear cells were isolated and tested by ELISpot for circulating IgM ANCA B cells. To determine whether infection affected IgM ANCA levels, we studied non-AAV patients with bacterial endocarditis or Staphylococcus aureus bacteraemia and measured IgM ANCA levels over time. IgM ANCA is detectable in both healthy individuals and patients with AAV and the titres decreased with increasing age. Circulating IgM ANCA B cells were identified by ELISpot. In the presence of infection, we could not find a significant change in IgM ANCA levels. We report the presence of low-level specific IgM ANCA in the sera of healthy individuals and in patients with ANCA-associated vasculitis. Bacterial infection did not affect the level of IgM ANCA in this small study.

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Acknowledgements

We acknowledge the support from the Royal Adelaide Hospital Research Committee. We also thank the generosity of patients and healthy individuals who participated in this study. Thank you to Dr J Weislander of Department of Autoimmunology, Statens Seruminstitut, Copenhagen, Denmark for the gift of anti-PR3 rabbit polyclonal antibody.

Funding

This work was supported by the Royal Adelaide Hospital Renal research fund and the Royal Hobart Hospital Renal research fund.

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Authors and Affiliations

  1. Department of Nephrology, Royal Hobart Hospital, Liverpool Street, Hobart, Tasmania, 7000, Australia

    LS Jeffs, PG Tan & E Davey

  2. Department of Renal Medicine, Royal Adelaide Hospital, Adelaide, Australia

    CA Peh & PR Hurtado

  3. Faculty of Medical and Health Sciences, University of Adelaide, Adelaide, Australia

    CA Peh, A Nelson, GB Perkins & PR Hurtado

  4. Department of Cardiology, Royal Adelaide Hospital, Adelaide, Australia

    A Nelson

  5. Menzies Institute for Medical Research, Department of Statistics, University of Tasmania, Liverpool Street, Hobart, Tasmania, 7000, Australia

    K Chappell

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Contributions

PRH, LJ and CAP conceived the study, performed the experiments and wrote the ethics applications.

PRH, AN, PT, ED, GBP, LJ and CAP assisted in patient sample collection and processing.

AN, PT, ED assisted with patient identification and sample collection.

PRH and KC created all figures.

KC performed all statistical analysis.

LJ wrote the manuscript draft.

All authors edited and contributed to the final draft.

Corresponding author

Correspondence to LS Jeffs.

Ethics declarations

This study complies with the Declaration of Helsinki. Both the University of Adelaide and University of Tasmania ethics committees provided approval. All patients gave informed consent before enrolment and blood collection.

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The authors declare that they have no conflict of interest.

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Jeffs, L., Peh, C., Nelson, A. et al. IgM ANCA in healthy individuals and in patients with ANCA-associated vasculitis. Immunol Res 67, 325–336 (2019). https://doi.org/10.1007/s12026-019-09091-x

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