Crohn's disease patients have specific IgG antibodies to human bacterial flagellins
Knowledge of the specific flagellins that drive the pathogenic immune response in Crohn's disease is a step toward a potential preventive treatment
2021-05-05
(Press-News.org) BIRMINGHAM, Ala. - Last year, Charles O. Elson, M.D., demonstrated a potential preventive treatment for Crohn's disease, a form of inflammatory bowel disease. He used a mouse model that included immune-reactive T cells from patients with Crohn's disease in a flagellin peptide-specific immunotherapy. This study provided proof-of-principle that a flagellin-directed immunotherapy might provide similar benefits in patients.
Now University of Alabama at Birmingham researchers have moved a step closer to possible clinical testing of this treatment, say Elson and co-first authors Katie Alexander, Ph.D., and Qing Zhao, M.D., Ph.D. Their study, published in the journal
Gastroenterology, is the first to describe IgG antibodies in Crohn's disease specific for human-derived flagellins of bacteria belonging to the Lachnospiraceae family. Knowledge of the specific flagellin epitopes that drive the pathogenic adaptive immune response in Crohn's disease is necessary information for Elson's potential triple-punch Crohn's disease treatment. Goals of the treatment are removing or exhausting pathogenic T memory cells and increasing the number of immunomodulatory T regulatory cells.
Elson is a professor, Alexander an assistant professor and Zhao a postdoctoral fellow in the UAB Department of Medicine Division of Gastroenterology and Hepatology.
Crohn's disease and ulcerative colitis -- another type of inflammatory bowel disease -- are characterized by dysregulated adaptive immune responses to the microbiota in genetically susceptible individuals, but the human specificity of these responses had so far been largely undefined. Mouse microbiota flagellins have previously been defined as immunodominant antigens in Crohn's disease.
Flagellins are building blocks of the hairlike motility flagella that extend from the bacterial cell wall. Flagellin is a potent immune activator and antigen, and it is the only known microbial protein that has three receptors for innate immunity encoded in the host genome, in addition to immunoglobulin and T cell receptors.
The UAB researchers individually probed blood sera from 87 healthy volunteers, 152 patients with Crohn's disease and 170 patients with ulcerative colitis. They used protein arrays of microbiota bacterial flagellins of both mouse and human origin, and they analyzed sera for IgG and IgA antibody responses.
They found selective patterns of antibody reactivity to microbiota flagellins among the inflammatory bowel disease patients.
The Crohn's disease patients -- but not the ulcerative colitis patients -- had augmented serum IgG antibodies to Lachnospiraceae flagellins from various species of Roseburia and one species of Eubacterium. These bacteria are normal residents in the human ileum, the third segment of the small intestine. A subset of the Crohn's disease patients had very high responses, with antibodies against more than 10 different flagellins.
For that subset of Crohn's disease patients, the multiflagellin hyper-reactivity was associated with indications of severe dysregulated immune response. Patients in the subset had: 1) elevated flagellin-specific T memory cells; 2) a reduced ratio of flagellin-reactive T regulatory to T effector cells; and 3) a high frequency of disease complications.
"Thus," Elson said, "Crohn's disease patients displayed a strong adaptive immune response to human-derived Lachnospiraceae flagellins, which may be targeted for prognosis and future personalized therapies."
INFORMATION:
Co-authors with Alexander, Zhao and Elson in the study, "Human microbiota flagellins drive adaptive immune responses in Crohn's disease," are Meagan Reif, Peter J. Mannon and Lennard Wayne Duck, UAB Department of Medicine; and Alexander F. Rosenberg, UAB Department of Microbiology.
Support came from Litwin IBD Pioneers grant 32655, Crohn's and Colitis Foundation of America; Department of Veterans Affairs grant CX0001530; National Institutes of Health grant AI007051; and a Synergy Award from the Rainin Foundation.
At UAB, Elson holds the Basil I. Hirschowitz Endowed Chair in Gastroenterology.
[Attachments] See images for this press release:
ELSE PRESS RELEASES FROM THIS DATE:
2021-05-05
Researchers have created a probe that glows when it detects an enzyme associated with issues that can lead to blood clots and strokes.
The team of researchers, from the Department of Chemistry and the National Lung and Heart Institute at Imperial College London, demonstrated that their probe quickly and accurately detects the enzyme in modified E. Coli cells.
They are now expanding this proof-of-concept study, published in the Journal of the American Chemical Society and funded by the British Heart Foundation (BHF), with the hope of creating rapid tests for cardiovascular problems and a new way to track long-term conditions.
The build-up of plaque in the arteries - known as atherosclerosis - can lead to coronary artery ...
2021-05-05
Biodiversity is of crucial importance to the marine ecosystem. The prohibition of trawling activities in the Hong Kong marine environment for two and a half years has significantly improved biodiversity, an inter-university study led by City University of Hong Kong (CityU) has found. Research results showed that the trawl ban could restore and conserve biodiversity in tropical coastal waters.
The research team was led by Professor Kenneth Leung Mei-yee, CityU's Director of the State Key Laboratory of Marine Pollution (SKLMP) and Chair Professor in the Department ...
2021-05-05
Researchers at CRANN (The Centre for Research on Adaptive Nanostructures and Nanodevices), and the School of Physics at Trinity College Dublin, today announced that a magnetic material developed at the Centre demonstrates the fastest magnetic switching ever recorded.
The team used femtosecond laser systems in the Photonics Research Laboratory at CRANN to switch and then re-switch the magnetic orientation of their material in trillionths of a second, six times faster than the previous record, and a hundred times faster than the clock speed of a personal computer.
This discovery demonstrates the potential of the material for a new generation of energy efficient ultra-fast computers and data storage systems.
The researchers ...
2021-05-05
Despite being home to the earliest signs of modern human behaviour, early evidence of burials in Africa are scarce and often ambiguous. Therefore, little is known about the origin and development of mortuary practices in the continent of our species' birth. A child buried at the mouth of the Panga ya Saidi cave site 78,000 years ago is changing that, revealing how Middle Stone Age populations interacted with the dead.
Panga ya Saidi has been an important site for human origins research since excavations began in 2010 as part of a long-term partnership between archaeologists from the Max Planck Institute for the Science of Human ...
2021-05-05
AMHERST, Mass. - The world is currently on track to exceed three degrees Celsius of global warming, and new research led by the University of Massachusetts Amherst's Rob DeConto, co-director of the School of Earth & Sustainability, shows that such a scenario would drastically accelerate the pace of sea-level rise by 2100. If the rate of global warming continues on its current trajectory, we will reach a tipping point by 2060, past which these consequences would be "irreversible on multi-century timescales."
The new paper, published today in Nature, models the impact of several different warming scenarios on the Antarctic Ice Sheet, including the Paris Agreement target of two degrees Celsius of warming, an aspirational 1.5 degree scenario, ...
2021-05-05
In 1 to 2 percent of cancer cases, the primary site of tumor origin cannot be determined. Because many modern cancer therapeutics target primary tumors, the prognosis for a cancer of unknown primary (CUP) is poor, with a median overall survival of 2.7-to-16 months. In order to receive a more specific diagnosis, patients often must undergo extensive diagnostic workups that can include additional laboratory tests, biopsies and endoscopy procedures, which delay treatment. To improve diagnosis for patients with complex metastatic cancers, especially those in low-resource settings, researchers from the Mahmood Lab at the Brigham and Women's Hospital developed an artificial intelligence (AI) system that uses routinely acquired histology slides to accurately find the origins of metastatic ...
2021-05-05
The Antarctic ice sheet is much less likely to become unstable and cause dramatic sea-level rise in upcoming centuries if the world follows policies that keep global warming below a key END ...
2021-05-05
Mitochondria either split in half to multiply within the cell, or cut off their ends to get rid of damaged material. That's the take-away message from EPFL biophysicists in their latest research investigating mitochondrial fission. It's a major departure from the classical textbook explanation of the life cycle of this well-known organelle, the powerhouse of the cell. The results are published today in Nature.
"Until this study, it was poorly understood how mitochondria decide where and when to divide," says EPFL biophysicist Suliana Manley and senior author of the study.
The big question : regulating mitochondrial fission
Mitochondrial fission is important for the proliferation of mitochondria, which is fundamental for cellular growth. As a cell gets bigger, ...
2021-05-05
The discovery of the earliest human burial site yet found in Africa, by an international team including several CNRS researchers1, has just been announced in the journal Nature. At Panga ya Saidi, in Kenya, north of Mombasa, the body of a three-year-old, dubbed Mtoto (Swahili for 'child') by the researchers, was deposited and buried in an excavated pit approximately 78,000 years ago. Through analysis of sediments and the arrangement of the bones, the research team showed that the body had been protected by being wrapped in a shroud made of perishable material, and that the head had likely rested on an object also of perishable material. Though there are no signs of offerings or ochre, both common at more recent burial ...
2021-05-05
Among the upper echelons of academic surgery, Black and Latinx representation has remained flat over the past six years, according to a study published today in JAMA Surgery by researchers at Virginia Commonwealth University Massey Cancer Center and University of Florida Health.
The study tracked trends across more than 15,000 faculty in surgery departments across the U.S. between 2013-2019. Although the data revealed modest diversity gains among early-career faculty during this period, especially for Black and Latina women, the percentage of full professors and department chairs identifying as Black or Latinx continued to hover in the single digits. ...
LAST 30 PRESS RELEASES:
[Press-News.org] Crohn's disease patients have specific IgG antibodies to human bacterial flagellins
Knowledge of the specific flagellins that drive the pathogenic immune response in Crohn's disease is a step toward a potential preventive treatment
