Identification of a novel antibody associated with autoimmune pancreatitis.
BACKGROUND
Autoimmune pancreatitis is characterized by an inflammatory process that leads to organ dysfunction. The cause of the disease is unknown. Its autoimmune origin has been suggested but never proved, and little is known about the pathogenesis of this condition.


METHODS
To identify pathogenetically relevant autoantigen targets, we screened a random peptide library with pooled IgG obtained from 20 patients with autoimmune pancreatitis. Peptide-specific antibodies were detected in serum specimens obtained from the patients.


RESULTS
Among the detected peptides, peptide AIP(1-7) was recognized by the serum specimens from 18 of 20 patients with autoimmune pancreatitis and by serum specimens from 4 of 40 patients with pancreatic cancer, but not by serum specimens from healthy controls. The peptide showed homology with an amino acid sequence of plasminogen-binding protein (PBP) of Helicobacter pylori and with ubiquitin-protein ligase E3 component n-recognin 2 (UBR2), an enzyme highly expressed in acinar cells of the pancreas. Antibodies against the PBP peptide were detected in 19 of 20 patients with autoimmune pancreatitis (95%) and in 4 of 40 patients with pancreatic cancer (10%). Such reactivity was not detected in patients with alcohol-induced chronic pancreatitis or intraductal papillary mucinous neoplasm. The results were validated in another series of patients with autoimmune pancreatitis or pancreatic cancer: 14 of 15 patients with autoimmune pancreatitis (93%) and 1 of 70 patients with pancreatic cancer (1%) had a positive test for anti-PBP peptide antibodies. When the training and validation groups were combined, the test was positive in 33 of 35 patients with autoimmune pancreatitis (94%) and in 5 of 110 patients with pancreatic cancer (5%).


CONCLUSIONS
The antibody that we identified was detected in most patients with autoimmune pancreatitis but also in some patients with pancreatic cancer, making it an imperfect test to distinguish between these two conditions.
Frulloni
Luca
L
Section of Gastroenterology, University of Verona, Verona, Italy.
Lunardi
Claudio
C
Simone
Rita
R
Dolcino
Marzia
M
Scattolini
Chiara
C
Falconi
Massimo
M
Benini
Luigi
L
Vantini
Italo
I
Corrocher
Roberto
R
Puccetti
Antonio
A
D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000097:blood / Q000175:diagnosis*; D001426:Bacterial Proteins / Q000737:chemistry; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000737:chemistry; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis; D050500:Pancreatitis, Chronic / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D019151:Peptide Library; D011485:Protein Binding; D012372:ROC Curve; D012680:Sensitivity and Specificity; D017386:Sequence Homology, Amino Acid; D012698:Serologic Tests; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry
D000907:Antibodies, Bacterial; D001323:Autoantibodies; D001426:Bacterial Proteins; D015415:Biomarkers; D002352:Carrier Proteins; D007074:Immunoglobulin G; D009842:Oligopeptides; D019151:Peptide Library; C545330:SKDERRF; C084529:plasminogen-binding protein, bacteria; D044767:Ubiquitin-Protein Ligases