Antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis after immunisation with bacterial proteins.
OBJECTIVE
There is circumstantial evidence for a role for infections in the development of the small vessel vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA). The aim of this study was to determine whether the immunisation of rats with bacterial proteins could result in circulating ANCA, T cells with specificity for ANCA antigens, and a systemic vasculitis.


METHODS
Adult male Wistar rats were immunised with pasteurised sonicated S. aureus (n = 7), E. coli (n = 8), purified protein derivative (PPD, n = 5), myeloperoxidase (MPO, n = 5) or phosphate-buffered saline (PBS, n = 5), in complete and in incomplete Freund's adjuvant. ANCA were assayed by indirect immunofluorescent (IIF) examination of normal rat neutrophils, and in ELISAs using human proteinase 3 (PR3), MPO and bactericidal/permeability-inreasing protein (BPI). The T cell response to PR3, MPO and BPI was assessed by a whole blood T cell proliferative assay in vitro, and by a delayed type hypersensitivity (DTH) response in vivo. Kidney and bowel were examined histologically for evidence of vasculitis and colitis.


RESULTS
One rat from each group immunised with S. aureus or E. coli developed pauciimmune segmental glomerular sclerosis. The rat immunised with E. coli had additionally an arteritis affecting renal interlobular and gut vessels. This rat had circulating C-ANCA, that produced granular cytoplasmic neutrophil fluorescence with central accentuation, but the target antigen could not be determined in ELISAs using human PR3, MPO or BPI. In animals immunised with S. aureus or E. coli, there was no significant T cell proliferative or DTH response specific for human PR3, MPO or BPI.


CONCLUSIONS
The development of ANCA and vasculitis in a rat immunised with bacterial proteins indicates that the relationship between infections and ANCA should be investigated further.
Savige
J
J
University of Melbourne, Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia. jsavige@austin.unimelb.edu.au
Nassis
L
L
Cooper
T
T
Paspaliaris
B
B
Martinello
P
P
MacGregor
D
D
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins / Q000276:immunology*; D001798:Blood Proteins / Q000276:immunology; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes; D004926:Escherichia coli / Q000276:immunology; D019084:Fluorescent Antibody Technique, Indirect; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007114:Immunization; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins; D053146:Myeloblastin; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D009195:Peroxidase / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014657:Vasculitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D019268:Antibodies, Antineutrophil Cytoplasmic; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D001798:Blood Proteins; D000939:Epitopes; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin