Transforming growth factor-beta (TGF-beta) expression and interaction with proteinase 3 (PR3) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Clin Exp Immunol. 1996 Jul;105(1):104-11. doi: 10.1046/j.1365-2249.1996.d01-715.x.


TGF-beta is a multifunctional cytokine modulating the onset and course of autoimmune diseases as shown in experimental models. The aim of this study was to investigate TGF-beta expression in ANCA-associated vasculitis (AAV), and the possible interactions of this cytokine with lysosomal enzymes identified as ANCA autoantigens (e.g. PR3). This included TGF-beta effects on the translocation of the lysosomal enzymes to the cell surface of polymorphonuclear neutrophils (PMN), and the presumed activation of non-bioactive, latent TGF-beta by these enzymes. Patients with various types of systemic vasculitis (SV) were studied, including three different types of AAV (Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS) and microscopic polyangiitis (MPA)). Regardless of the type of assay applied, the TGF-beta 1 isoform was found to be over-expressed in SV, including AAV, and to correlate with disease activity as shown for WG. Mean TGF-beta 1 plasma levels in AAV patients ranged from 8.9 ng/ml (WG) to 13.3 ng/ml (CSS) (control 4.2 ng/ml; P < 0.01), while TGF-beta 2 levels were not elevated. Flow cytometry analysis showed TGF-beta 1 to be a potent translocation factor for PR3 comparable to other neutrophil-activating factors such as IL-8. PR3 membrane expression on primed PMN increased by up to 51% after incubation with TGF-beta 1. PR3 itself was revealed as a potent activator of latent TGF-beta, thus mediating bioeffects of this cytokine. These findings, together with other features of TGF-beta such as induction of angiogenesis and its strong chemotactic capacity, indicate that TGF-beta might serve as a proinflammatory factor in SV, especially in AAV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Antineutrophil Cytoplasmic
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / immunology*
  • Base Sequence
  • Churg-Strauss Syndrome / blood
  • Churg-Strauss Syndrome / genetics
  • Churg-Strauss Syndrome / immunology*
  • Cytoplasm / immunology
  • Granulomatosis with Polyangiitis / blood
  • Granulomatosis with Polyangiitis / genetics
  • Granulomatosis with Polyangiitis / immunology*
  • Humans
  • Ion Pumps / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lysosomes / enzymology
  • Molecular Sequence Data
  • Myeloblastin
  • Polyarteritis Nodosa / blood
  • Polyarteritis Nodosa / immunology
  • RNA, Messenger / biosynthesis
  • Serine Endopeptidases / immunology
  • Serine Endopeptidases / pharmacology*
  • Transforming Growth Factor beta / biosynthesis*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / pharmacology


  • Antibodies, Antineutrophil Cytoplasmic
  • Autoantibodies
  • Ion Pumps
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Serine Endopeptidases
  • Myeloblastin