PR3-ANCA: a promising biomarker in primary sclerosing cholangitis (PSC).
OBJECTIVE
The only recognized biomarker for primary sclerosing cholangitis (PSC) is atypical anti-neutrophil cytoplasmic antibodies (aANCA), which, in addition to having low sensitivity and specificity, is an indirect immunofluorescence (IIF) test lacking the advantages of high throughput and objectivity. Recent reports have shown that antibodies to proteinase-3 (PR3-ANCA) might add diagnostic value in inflammatory bowel disease (IBD), specifically in ulcerative colitis (UC). As PSC is associated with IBD, the objective of this study was to evaluate the frequency and clinical significance of PR3-ANCA in a large cohort of patients.


METHODS
A total of 244 PSC and 254 control [autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), hepatitis C viral infection (HCV), hepatitis B viral infection (HBV), and healthy controls] sera and their clinical correlations were retrospectively analyzed for PR3-ANCA determined by ELISA and a new chemiluminescence immunoassay (CIA). Testing was also performed for aANCA by IIF.


RESULTS
When measured by CIA, PR3-ANCA was detected in 38.5% (94/244) of PSC patients compared to 10.6% (27/254) controls (p<0.0001). By ELISA, PR3-ANCA was detected in 23.4% (57/244) of PSC patients compared to 2.7% (6/254) controls (p<0.0001). PR3-ANCA in PSC patients was not associated with the presence or type of underlying IBD, and, in fact, it was more frequent in Crohn's disease (CD) patients with PSC than previously reported in CD alone. PR3-ANCA in PSC measured by CIA correlated with higher liver enzymes.


CONCLUSIONS
PR3-ANCA is detected in a significant proportion of PSC patients compared to other liver diseases including PBC and AIH. PR3-ANCA is associated with higher liver enzyme levels in PSC, and is not solely related to underlying IBD.
Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Laura M
LM
Stinton
Inova Diagnostics, Inc., San Diego, California, United States of America.
Chelsea
C
Bentow
Inova Diagnostics, Inc., San Diego, California, United States of America.
Michael
M
Mahler
Inova Diagnostics, Inc., San Diego, California, United States of America.
Gary L
GL
Norman
Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Bertus
B
Eksteen
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Andrew L
AL
Mason
Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Gilaad G
GG
Kaplan
Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Bjorn
B
Lindkvist
Centre for Liver Research, NIHR Biomedical Research Unit, University of Birmingham, Birmingham, United Kingdom.
Gideon M
GM
Hirschfield
Department of General, Transplant and Liver Surgery, Warsaw Medical University, Warsaw, Poland; Liver Research Laboratories, Pomeranian Medical University, Szczecin, Poland.
Piotr
P
Milkiewicz
University Health Network, Division of Gastroenterology, Toronto Western Hospital, Toronto, Ontario, Canada.
Angela
A
Cheung
University Health Network, Division of Gastroenterology, Toronto Western Hospital, Toronto, Ontario, Canada.
Harry L A
HL
Janssen
Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Marvin J
MJ
Fritzler
D000704:Analysis of Variance; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000175:diagnosis*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007118:Immunoassay; D015212:Inflammatory Bowel Diseases / Q000097:blood; D008163:Luminescent Measurements; D053146:Myeloblastin / Q000097:blood*
D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D053146:Myeloblastin