Autoimmune pancreatitis can make IgG4-RD more complex to treat
Greater clinical complexity seen in patients with affected pancreas, bile ducts
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People with the inflammatory condition IgG4-related disease (IgG4-RD) face a more severe form of illness when their pancreas is affected, according to a single-center study in China.
Specifically, patients who develop autoimmune pancreatitis (AIP) show worse clinical features, especially if the disease also involves the bile ducts, suggesting that pancreatic involvement drives a more body-wide immune response.
IgG4-AIP patients with bile duct involvement also had markedly elevated levels of immune cells and biomarkers for liver damage and inflammation compared with those with no signs of bile duct disease.
Study objectives and design
“This study will provide crucial scientific evidence for clinicians to enhance their understanding of the clinical [variability] of IgG4-AIP and to support the development of personalized treatment strategies,” researchers wrote.
The study, “A retrospective study on pancreatic and extra-pancreatic characteristics of IgG4-related disease,” was published in Clinical Rheumatology.
In IgG4-RD, immune cells, particularly those that produce IgG4-type antibodies, infiltrate tissues, leading to inflammation, scarring, and the formation of tumor-like masses in one or more organs.
IgG4-AIP, commonly referred to as type 1 autoimmune pancreatitis, is a frequent manifestation of IgG4-RD. It occurs when the body’s immune system wrongly attacks the pancreas, causing inflammation and scarring.
Pancreatic involvement in IgG4-RD is commonly associated with involvement of the bile ducts, representing an IgG4-RD clinical profile called pancreato-hepatobiliary disease.
However, “only a limited number of studies have conducted in-depth analyses regarding the clinical characteristics, treatment strategies, and prognosis associated with IgG4-AIP,” the researchers wrote.
With this in mind, the team of researchers in China retrospectively analyzed data from 82 adults who were diagnosed with IgG4-RD at a single Chinese hospital. Mean age at diagnosis was 59.13 years (range, 35-89), and most (76.8%) were men.
A total of 40 participants (48.78%) had AIP, while the remaining 42 (51.22%) did not have AIP. Significantly more men had pancreatic involvement than those without (87.5% vs. 66.67%), a finding that “warrants further investigation to elucidate the gender differences observed among various affected organs in IgG4-RD,” the team wrote.
IgG4-AIP associated with severe, multi-organ disease
The AIP group was significantly more likely to show involvement of two or more organs than the non-AIP group (72.5% vs. 42.86%), suggesting the “systemic immune response elicited by pancreatic involvement is more pronounced,” the researchers wrote.
The bile ducts were affected more frequently in IgG4-AIP patients than in those without pancreas involvement (50% vs. 2.38%). In contrast, the AIP group was less likely to have lung involvement (5% vs. 35.71%) or salivary gland involvement (0% vs. 23.81%).
This finding may be explained by the “anatomical proximity between the pancreas and the [bile duct] system,” the scientists wrote.
A significantly higher proportion of people with AIP had blood IgG4 levels that were two to five times higher than the upper limit of normal (68.57% vs. 46.88%), while those without AIP were more likely to have normal IgG4 levels (25% vs. 5.71%).
The study also found IgG4-AIP patients with bile duct involvement had higher blood levels of two types of immune cells (basophils and eosinophils), and of biomarkers of liver damage (alkaline phosphatase and bilirubin) and inflammation (erythrocyte sedimentation rate).
This suggests that IgG4-AIP is associated with “a more severe stage of the disease, where persistent inflammatory stimuli keep the immune system in an activated state,” the researchers wrote.
Imaging studies in the AIP group showed that the most common pancreatic abnormalities were widespread enlargement, predominantly with a “sausage-like” shape (57.5%) and focal enlargement of the thicker end of the pancreas (42.5%).
Bile duct involvement ranged from more localized, affecting only the bile ducts outside the liver, to more widespread, affecting both those outside and inside the liver.
About 17.5% of IgG4-AIP patients showed signs of kidney involvement, while 5% had lung involvement. Retroperitoneal fibrosis, referring to tissue scarring in the area in the back of the abdomen, was detected in two patients (5%), while another two (5%) showed liver involvement.
“IgG4-AIP presents with more complex clinical characteristics,” the team concluded. “Clinicians should develop a thorough understanding of these features and formulate individualized diagnostic and therapeutic strategies to improve patient outcomes.”
