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Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes
  1. Ymke M van der Geld1,
  2. Thomas Hellmark2,
  3. Daina Selga2,
  4. Peter Heeringa3,
  5. Minke G Huitema1,
  6. Pieter C Limburg1,
  7. Cees G M Kallenberg1
  1. 1
    University Medical Center Groningen, Department of Rheumatology and Clinical immunology, Groningen, The Netherlands
  2. 2
    Lund University hospital, Department of Nephrology, Lund, Sweden
  3. 3
    University Medical Center Groningen, Department of Pathology and Laboratory Medicine, Medical Biology Section, University of Groningen, The Netherlands
  1. Professor C G M Kallenberg, Department of Clinical immunology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; c.g.m.kallenberg{at}int.umcg.nl

Abstract

Aim: In this study, we employed chimeric human/mouse Proteinase 3 (PR3) proteins as tools to induce an autoantibody response to PR3 in rats and mice.

Method: Rats and mice were immunised with recombinant human PR3 (HPR3), recombinant murine PR3 (mPR3), single chimeric human/mouse PR3 (HHm, HmH, mHH, mmH, mHm, Hmm) or pools of chimeric proteins. Antibodies to mPR3 and HPR3 were measured by ELISA. Antibodies to rat PR3 were determined by indirect immunofluorescence (IIF) on rat white blood cells. Urinalysis was performed by dipstick analysis. Kidney and lung tissue was obtained for pathological examination.

Results: In mice, immunisation with the chimeric human/mouse PR3 Hmm led to an autoantibody response to mPR3. Rats immunised with the chimeric human/mouse PR3 Hmm, HmH and mmH, or a pool of the chimeric human/mouse PR3 proteins, produced antibodies selectively binding to rat granulocytes as detected by IIF. No gross pathological abnormalities could be detected in kidney or lungs of mice or rats immunised with chimeric human/mouse PR3.

Conclusion: Immunisation with chimeric human/mouse proteins induces autoantibodies to PR3 in rats and mice. Chimeric proteins can be instrumental in developing experimental models for autoimmune diseases.

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Footnotes

  • Competing interests: None declared.

  • Abbreviations:
    ANCA
    antineutrophil cytoplasmic antibodies
    BN
    Brown Norway
    BSA
    bovine serum albumin
    HPR3
    human proteinase 3
    MPO
    myeloperoxidase
    mPR3
    murine proteinase 3
    PR3
    proteinase 3
    WG
    Wegener’s granulomatosis
    WKY
    Wistar Kyoto

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