Discerning pancreatic cancer from pancreatitis

Test shows patients with autoimmune pancreatitis more likely to have telltale antibody

A new test puts doctors one step closer to distinguishing between pancreatic cancer and a troublesome inflammation of the organ called autoimmune pancreatitis. Making that call can be difficult because in autoimmune pancreatitis, a lump of hardened tissue can form in the pancreas and is sometimes mistaken for a tumor.

Reporting in the November 26 New England Journal of Medicine, researchers in Italy show that patients who have been diagnosed with autoimmune pancreatitis are very likely to make antibodies that mistakenly attack a harmless enzyme found in the pancreas. In this disease, a person’s own immune troops target pancreatic tissue, causing inflammation and damaging this vital organ.

In contrast, these antibodies were absent in healthy people and rare in pancreatic cancer patients, says study coauthor Antonio Puccetti, a physician and immunologist at Giannina Gaslini Institute in Genoa.

Short of a biopsy, there is currently no single test that physicians can use to identify autoimmune pancreatitis and distinguish it from pancreatic cancer.

Roughly one in 10 surgeries to remove a pancreatic tumor find a hardened mass arising from autoimmune pancreatitis — not cancer. These lumps result from inflammation-based tissue damage.

In the new study, Puccetti and his colleagues analyzed blood from patients with autoimmune pancreatitis, adding an array of proteins to see whether these patients had made antibodies against any of the compounds. Antibodies targeting a bacterial compound called plasminogen binding protein, or PBP, stood out.
Next, the scientists tested blood from healthy people and from pancreatic cancer patients for antibodies directed against PBP.

The tests showed that 33 of 35 people with autoimmune pancreatitis had made antibodies against PBP, compared with only five of 120 pancreatic cancer patients and none of 40 healthy people.

When the researchers compared PBP with compounds typically found in the human pancreas, they found a match — an enzyme called UBR2.

The cause of autoimmune pancreatitis is unknown. But a closer look at the biology underlying these new findings suggests it might arise from a coincidence in nature, Puccetti says.

PBP is found on a bacterium, Helicobacter pylori, that is a common hitchhiker in the human stomach. PBP’s similarity to UBR2 stems from a stretch of amino acids that shows up on both. Puccetti says the human enzyme UBR2 seems to get targeted by the same antibodies directed against PBP. Thus, in some people, this molecular mimicry means that cells making UBR2 enzymes risk winding up in the crosshairs of an attack by the immune system.

“Apparently these auto-antibodies cross-react with the [pancreatic] cells and damage the tissue,” says William Brugge, a physician at Harvard Medical School in Boston.

Since a few people with pancreatic cancer also tested positive for antibodies to PBP, this test constitutes a “good but not perfect” means for distinguishing between the cancer and pancreatitis, Brugge says.

Puccetti asserts that the test “is of great help in discriminating the disease from pancreatic cancer.” He says it’s likely to be used in conjunction with other tests. “The antibody test should precede the biopsy, which remains the best diagnostic test.”

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