Diagnostic accuracy of atypical p-ANCA in autoimmune hepatitis using ROC- and multivariate regression analysis.
BACKGROUND
Antineutrophil cytoplasmic antibodies (atypical p-ANCA) are detected at high prevalence in sera from patients with autoimmune hepatitis (AIH), but their diagnostic relevance for AIH has not been systematically evaluated so far.


METHODS
Here, we studied sera from 357 patients with autoimmune (autoimmune hepatitis n=175, primary sclerosing cholangitis (PSC) n=35, primary biliary cirrhosis n=45), non-autoimmune chronic liver disease (alcoholic liver cirrhosis n=62; chronic hepatitis C virus infection (HCV) n=21) or healthy controls (n=19) for the presence of various non-organ specific autoantibodies. Atypical p-ANCA, antinuclear antibodies (ANA), antibodies against smooth muscles (SMA), antibodies against liver/kidney microsomes (anti-Lkm1) and antimitochondrial antibodies (AMA) were detected by indirect immunofluorescence microscopy, antibodies against the M2 antigen (anti-M2), antibodies against soluble liver antigen (anti-SLA/LP) and anti-Lkm1 by using enzyme linked immunosorbent assays. To define the diagnostic precision of the autoantibodies, results of autoantibody testing were analyzed by receiver operating characteristics (ROC) and forward conditional logistic regression analysis.


RESULTS
Atypical p-ANCA were detected at high prevalence in sera from patients with AIH (81%) and PSC (94%). ROC- and logistic regression analysis revealed atypical p-ANCA and SMA, but not ANA as significant diagnostic seromarkers for AIH (atypical p-ANCA: AUC 0.754+/-0.026, odds ratio [OR] 3.4; SMA: 0.652+/-0.028, OR 4.1). Atypical p-ANCA also emerged as the only diagnostically relevant seromarker for PSC (AUC 0.690+/-0.04, OR 3.4). None of the tested antibodies yielded a significant diagnostic accuracy for patients with alcoholic liver cirrhosis, HCV or healthy controls.


CONCLUSIONS
Atypical p-ANCA along with SMA represent a seromarker with high diagnostic accuracy for AIH and should be explicitly considered in a revised version of the diagnostic score for AIH.
Terjung
B
B
Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. birgit.terjung@ukb.uni-bonn.de
Bogsch
F
F
Klein
R
R
Söhne
J
J
Reichel
C
C
Wasmuth
J-C
JC
Beuers
U
U
Sauerbruch
T
T
Spengler
U
U
D000293:Adolescent; D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000276:immunology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009130:Muscle, Smooth / Q000276:immunology; D012372:ROC Curve; D012044:Regression Analysis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D015415:Biomarkers