Imbalance of certain fatty molecules may signal disease severity in PSC
Ratio in blood may be biomarker for cholangitis, IBD: Study
An imbalance in the blood between long-chain and very long-chain ceramides — fatty molecules that help fine-tune the body’s inflammatory response — may help indicate disease severity in primary sclerosing cholangitis (PSC), a study from researchers in Germany suggests.
In patients who had both PSC and inflammatory bowel disease (IBD), the ratio of long-chain to very long-chain ceramides increased as cholangitis worsened, the data showed. IBD is an umbrella term for disorders that cause immune-mediated inflammation of the gastrointestinal tract. These conditions often occur alongside PSC.
“This study demonstrates that an altered [long-to-very-long-chain] ceramide balance is associated with disease severity in IBD, PSC-IBD, and PSC, highlighting its potential as a biomarker for [these conditions],” the researchers wrote.
Still, because the number of PSC patients involved in the study was small, “a confirmatory study is required,” the team added.
The study, “Elevated long-to-very-long-chain ceramide ratio correlates with disease severity in inflammatory bowel disease and primary sclerosing cholangitis,” was published in the journal Scientific Reports.
PSC is a chronic form of cholangitis that occurs when the bile ducts — tubes that carry bile, a digestive fluid, from the liver to the intestines — become progressively inflamed over time. This eventually causes slowed bile flow, or cholestasis, and liver damage.
Ceramides are a type of fatty molecules found in a cell’s membrane, where they help the cell respond to its environment. Involved in several cellular processes, including inflammation, these molecules come in different lengths. Long-chain ceramides (C16-C20) and very long-chain ceramides (C22-C26) appear to have opposite effects in the body.
Increasing evidence suggests these molecules play an important role in IBD and chronic liver damage. However, it’s not yet clear how different levels of these ceramides in the blood relate to how severe PSC and IBD are in patients.
Measuring ceramide levels in blood
To learn more, a team of researchers from University Hospital Regensburg measured eight types of ceramides and five types of hexosylceramides — ceramides with an added sugar — in the blood of both patients and healthy people. Their study involved seven adults with PSC, 57 with IBD, 13 with both PSC and IBD (PSC-IBD), and 16 healthy adults, who served as controls.
Regarding known markers of liver or bile duct damage, the PSC group had the highest levels of bilirubin and the liver enzymes GGT and AP. These levels were significantly higher than those seen in the IBD patients. People with PSC-IBD had significantly higher levels of bilirubin and AP than those with IBD alone.
The ratio of long-chain ceramides to very long-chain ceramides was significantly higher in the PSC, IBD, and PSC-IBD groups compared with healthy controls, meaning that patients in all groups had more long-chain ceramides relative to very long-chain ceramides.
“PSC-IBD patients also exhibited significantly lower total ceramide levels compared to PSC patients,” the team wrote.
[These findings indicate] that an imbalance in [long-chain] and [very long-chain] ceramide levels is associated with disease severity [in patients].
A higher long-to-very-long chain ceramide ratio was significantly associated with higher levels of inflammation markers in IBD patients, and with higher levels of GGT and AP in adults with PSC-IBD. This suggested more severe cholangitis.
“However, the PSC [group] was too small for meaningful statistical analysis,” the researchers noted.
These findings indicate “that an imbalance in [long-chain] and [very long-chain] ceramide levels is associated with disease severity,” the researchers wrote.
Results accurately distinguished PSC patients
Total levels of hexosylceramides were comparable between all groups, but two hexosylceramides types — called HexCer 18:1;O2/16:0 and 18:1;O2/24:1 — were significantly more abundant in PSC patients than in controls, the data showed. The levels of each of these hexosylceramides also helped researchers accurately distinguish patients diagnosed with PSC from all other groups, the study noted.
Specific ceramides and hexosylceramides, including HexCer 18:1;O2/24:1, were also linked to markers of damage and impaired liver function in the PSC-IBD group, per the data.
HexCer 18:1;O2/24:1 “was significantly elevated in PSC patients, who also had higher levels of GGT, AP, and bilirubin compared to those with PSC-IBD, further supporting its association with cholestasis,” the team wrote.
According to the researchers, “the increase in [blood] hexosylceramide species is a distinctive feature of PSC and merits further investigation as both a pathophysiological marker [reflecting disease mechanisms] and a potential noninvasive diagnostic tool.”
The team further noted that, while the study involved a small number of patients from a single center in Germany, its findings align with previous data showing that ACER3 — an enzyme involved in the metabolism of ceramides — is elevated in the liver of people with cholestasis, and may contribute to liver inflammation.
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