Identification of Novel Serum Autoantibodies for Differential Diagnosis of Autoimmune Pancreatitis and Pancreatic Ductal Adenocarcinoma

Abstract

The novel panel of AIP autoantibodies is promising to supplement the predictive tests for AIP of the currently known autoantigens and represent a basis for a combined blood test to differentiate AIP from PDAC in the future.

Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach

“…Some of these antibodies are organ-specific mainly against antigens from the pancreatic ducts and acini [28,30], whereas others are not organ-specific and directed against nuclear antigen (ANA). Recently, additional autoantibodies have been identified against pancreatic enzyme precursors in AIP patients [7]. The study also reported different expression of anti-pancreatic lipase and anti-transaldolase in the two AIP-subtypes.…”

“…Microarrays assembled of thousands of different proteins have been already reported and used to identify tumour associated autoantibodies in the context of colorectal cancer [25], bladder cancer [26], ovarian cancer, and pancreatic cancer [8,27]. Furthermore, several studies described elevated autoantibody concentrations in sera of patients with AIP including anti-lactoferrin [28,29], anti-carbonic anhydrase II, anti-carbonic anhydrase IV, anti-pancreas secretory trypsin inhibitor, anti-anionic and cationic trypsinogens, anti-amylase-1, anti-heat shock protein 10 and anti-plasminogen-binding protein peptide autoantibodies [7,18,30]. However, their performance as diagnostic markers is still under debate.…”

“…The ID correctness was confirmed by sequencing the PCR products, from which the relevant proteins were produced recombinantly. Of note, four of these proteins-annexin A4 (ANXA4), protease serine 1 (PRSS1), lactotransferrin (LTF) and peroxiredoxin 4 (PRDX 4)-were already previously reported as AIP autoantigens [7,18]. The normalized median log2 MFI for each candidate for the six compared groups are reported in Table 3.…”

“…Their release into the blood circulation and their assessment could aid early diagnosis of high-risk populations and assist the clinical management of patients. Tumour associated autoantibodies (TAAbs) are promising serum biomarkers for detection of early stage disease [7][8][9][10][11]. Indeed, TAAbs can be detected earlier before the disease progresses to an advanced, incurable stage.…”

Distinct pathophysiological cytokine profiles for discrimination between autoimmune pancreatitis, chronic pancreatitis, and pancreatic ductal adenocarcinoma

“…Applying a multiplex ELISA for IL-1β, IL-7, and G-CSF on patients’ serum would also allow AIP-2 to be distinguished from PDAC. Combining them with the recently identified gelatinases A and B and apolipoproteins Apo-AI and Apo-AII as discriminatory parameters [50–52] in a multiplex format, this could form the basis for a clinically applicable blood test, allowing reliable distinction between AIP and PDAC. This test would warrant immune-suppressive therapy without surgery for AIP patients and immediate surgical and chemotherapeutical treatment of PDAC patients.…”