Membrane proteinase 3 (mPR3) expression on neutrophils is not increased in localized Wegener's granulomatosis (WG) and Churg-Strauss syndrome (CSS).
OBJECTIVE
The aim of this study was to analyse mPR3 expression on neutrophils in two Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), namely WG (localised vs. generalised) and Churg-Strauss syndrome (CSS) and other inflammatory disorders, in order to evaluate (i) whether the pattern of mPR3 expression is specific for AAV and (ii) to assess whether the mPR3high status is associated with clinically distinct disease stages of WG (localised vs. generalised).


METHODS
Localised WG (n=15), generalised WG (n=55), Churg-Strauss Syndrome (CSS) (n=20), systemic lupus erythematosus (SLE) (n=15), Rheumatoid Arthritis (RA) (n=22) and healthy controls (n=30) were analysed. mPR3 and CD63 expression on surface of neutrophils were assessed by flow cytometric analysis on isolated neutrophils and whole blood.


RESULTS
In patients with genWG and SLE, an increased percentage of mPR3+ neutrophils and an elevated level of mPR3 expression compared to healthy controls were found (percentage: p=0.001, p=0.000; MFI ratio: p=0.038, p=0.019, respectively). There was no increased frequency of mPR3+ neutrophils in CSS. Within the group of WG, an elevated level of mPR3 expression was significantly associated with disease stage (genWG and not locWG), and in genWG with disease activity and the presence of ANCA.


CONCLUSIONS
The mPR3high status is associated with generalised WG and correlates with disease activity and ANCA status in generalised WG. An increased proportion of mPR3-positive neutrophils is not specific for AAV.
Holle
Julia U
JU
Department of Rheumatology and Clinical Immunology, Vasculitis Center, University Hospital Schleswig-Holstein and Klinikum Bad Bramstedt, Germany. holle@clinikumbb.de
Wu
Q J
QJ
Moosig
Frank
F
Gross
Wolfgang L
WL
Csernok
Elena
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D015267:Churg-Strauss Syndrome / Q000276:immunology* / Q000378:metabolism*; D000939:Epitopes; D005260:Female; D005434:Flow Cytometry; D014890:Granulomatosis with Polyangiitis / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index; D060149:Tetraspanin 30; D055815:Young Adult
D015703:Antigens, CD; D001324:Autoantigens; C554586:CD63 protein, human; D000939:Epitopes; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D053146:Myeloblastin