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Rats and mice immunized with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes
  1. Ymke M. van der Geld
  1. University Medical Center Groningen, Netherlands
    1. Thomas Hellmark
    1. Lund University Hospital, Sweden
      1. Daina Selga
      1. Lund University Hospital, Sweden
        1. Peter Heeringa
        1. University Medical Center Groningen, Netherlands
          1. Minke G. Huitema
          1. University Medical Center Groningen, Netherlands
            1. Piet Limburg
            1. University Medical Center Groningen, Netherlands
              1. Cees G.M. Kallenberg (c.g.m.kallenberg{at}int.umcg.nl)
              1. University Medical Center Groningen, Netherlands

                Abstract

                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. Rats and mice were immunized with either 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. In mice immunization with the chimeric human/mouse PR3 Hmm led to an autoantibody response to mPR3. Rats immunized 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 immunized with chimeric human/mouse PR3. In conclusion, immunization 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.

                • ANCA
                • autoantibodies
                • chimeric proteins
                • proteinase 3
                • vasculitis

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