Assay may identify autoimmune pancreatitis

Researchers have identified an antibody that is present in the serum of most patients who have autoimmune pancreatitis and may eventually help in the differential diagnosis of the disorder, according to a report in the New England Journal of Medicine.

Unfortunately, the antibody also was present in a few patients who had pancreatic cancer, so it cannot yet be used as the sole factor to distinguish between these two clinically similar diseases, said the University of Verona in Italy and associates.

The investigators developed an assay to detect the antibody in serum samples. The sensitivity and specificity of the assay were 94% and 95% respectively, when used in 35 patients who had autoimmune pancreatitis (AIP) and 110 who had pancreatic cancer, “suggesting that it is an imperfect test to rule out pancreatic cancer.”

A study to find a serologic marker that would discriminate between autoimmune pancreatitis and pancreatic adenocarcinoma. As many as 10% of patients who undergo pancreatic resection because they are thought to have cancer actually are found to have pancreatitis rather than cancer.

The researchers obtained immunoglobulins from serum samples of 20 patients with newly diagnosed autoimmune pancreatitis and compared them against samples in a peptide library to identify only peptides that may have been related to the pathogenesis of the disease. An AIP peptide was recognized by IgG in serum samples from 17 of the 20 patients, but not serum IgG from 40 healthy control subjects.

However, samples from 22 to 40 patients with pancreatic cancer (55%) and from 10 of 21 patients with alcohol-induced chronic pancreatitis (50%) also reacted with this peptide.

To better discriminate among these disorders, synthesized two AIP peptides and found that one of them was highly correlated with a PBP protein encoded by Helicobacter pylori, an infection that has been implicated in the pathogenesis of autoimmune pancreatitis. The investigators then synthesized the bacterial PBP peptide, and used it to create an assay with which to screen the serum samples.

This assay identified 19 of the 20 cases of autoimmune pancreatitis but did not react with samples from any healthy controls, with samples from 39 patients with other pancreatic diseases, or with samples autoimmune diseases.

However, the antibody also was recognized by 4 of the 40 patients with pancreatic cancer, the investigators said.

To validate these findings, the assay was used in another series of patients. Antibodies were found in 14 of 15 patients with autoimmune pancreatitis, and in 1 of 70 patients with pancreatic cancer in this validation group. When the study group and validation group were combined, the assay was positive in 33 of 35 patients with autoimmune pancreatitis and 5 of 110 patients with pancreatic cancer, for a sensitivity of 94% and a specificity of 95%.

Commented “This study is a provocative and important study that links the presence of antibodies to a peptide (AIP 1-7) to autoimmune pancreatitis.” The assay “showed much greater sensitivity and specificity compared to high IgG4 levels, which have also been used.”

“The test appears extremely promising as a diagnostic test for AIP, but needs to be confirmed prospectively in a diagnostic setting; unfortunately it may not be useful for excluding pancreatic cancer.

“Further studies needed to determine the exact relationship to H. pylori eradication therapy could reduce the antigenic load and help induce remission of AIP,” chief of the division of digestive and liver diseases and the Silberberg professor of medicine at Columbia University College of Physicians and Surgeons, New York.

The study showed that 81%-83% of AIP patients had secrological markers to H. pylori infection, much higher than any of the other control groups (44%-55%). However, no studies were performed to confirm the presence or absence of active infection, such as endoscopic biopsy or breath test.