NIH scientists discover genetic cause of rare allergy to vibrationFebruary 03, 2016
Scientists at the National Institutes of Health (NIH) have identified a genetic mutation responsible for a rare form of inherited hives induced by vibration, also known as vibratory urticaria. Running, hand clapping, towel drying or even taking a bumpy bus ride can cause temporary skin rashes in people with this rare disorder. By studying affected families, researchers discovered how vibration promotes the release of inflammatory chemicals from the immune system's mast cells, causing hives and other allergic symptoms.
Their findings, published online in the New England Journal of Medicine on Feb. 3, suggest that people with this form of vibratory urticaria experience an exaggerated version of a normal cellular response to vibration. The study was led by researchers at the National Institute of Allergy and Infectious Diseases (NIAID) and the National Human Genome Research Institute (NHGRI), both part of NIH.
"Investigating rare disorders such as vibratory urticaria can yield important insights into how the immune system functions and how it reacts to certain triggers to produce allergy symptoms, which can range from mild to debilitating," said NIAID Director Anthony S. Fauci, M.D. "The findings from this study uncover intriguing new facets of mast cell biology, adding to our knowledge of how allergic responses occur."
"This study illustrates the power of a multidisciplinary team, involving clinicians, geneticists and basic immunologists, to get to the heart of a medical mystery," said Dan Kastner, M.D., Ph.D., scientific director of the Intramural Research Program at NHGRI and a co-author of the study. "It also underscores the tremendous potential of new genomic techniques."
In addition to itchy red welts at the site of vibration on the skin, people with vibratory urticaria also sometimes experience flushing, headaches, fatigue, blurry vision or a metallic taste in the mouth. Symptoms usually disappear within an hour, but those affected may experience several episodes per day.
The current study involved three families in which multiple generations experienced vibratory urticaria. The NIH team evaluated the first family under an ongoing clinical protocol investigating urticarias induced by a physical trigger.
Mast cells, which reside in the skin and other tissues, release histamine and other inflammatory chemicals into the bloodstream and surrounding tissue in response to certain stimuli, a process known as degranulation. To assess potential mast cell involvement in vibratory urticaria, the researchers measured blood levels of histamine during an episode of vibration-induced hives. Histamine levels rose rapidly in response to vibration and subsided after about an hour, indicating that mast cells had released their contents. The researchers also observed increased tryptase, another marker of mast cell degranulation, in skin around the affected area.
"Notably, we also observed a small increase in blood histamine levels and a slight release of tryptase from mast cells in the skin of unaffected individuals exposed to vibration," said Hirsh Komarow, M.D., of NIAID's Laboratory of Allergic Diseases, the senior author of the study. "This suggests that a normal response to vibration, which does not cause symptoms in most people, is exaggerated in our patients with this inherited form of vibratory urticaria."
The NIH team realized that the first family's symptoms matched those of a different family described by researchers at Yale University in 1981. Through a collaboration with Yale, the NIH team obtained DNA samples from 25 members of that family. Two family members came to NIH for evaluation, and they put the scientists in contact with a third family with similar symptoms.
To identify the genetic basis of the disorder, the scientists performed genetic analyses, including DNA sequencing, on 36 affected and unaffected members from the three families. They found a single mutation in the ADGRE2 gene shared by family members with vibratory urticaria but not present in unaffected people. The scientists did not detect the ADGRE2 mutation in variant databases or in the DNA of more than 1,000 unaffected individuals with a similar genetic ancestry as the three families.
"This work marks, to the best of our knowledge, the first identification of a genetic basis for a mast-cell-mediated urticaria induced by a mechanical stimulus," said Dean Metcalfe, M.D., chief of NIAID's Laboratory of Allergic Diseases and a study co-author.
The ADGRE2 gene provides instructions for production of ADGRE2 protein, which is present on the surface of several types of immune cells, including mast cells. ADGRE2 is composed of two subunits--a beta subunit located within the cell's outer membrane, and an alpha subunit located on the outside surface of the cell. Normally, these two subunits interact, staying close together.
People with familial vibratory urticaria produce a mutated ADGRE2 protein in which this subunit interaction is less stable, the investigators found. After vibration, the alpha subunit of the mutant protein was no longer in close contact with the beta subunit. When the alpha subunit detaches from the beta subunit, the researchers suggest, the beta subunit produces signals inside mast cells that lead to degranulation, which causes hives and other allergy symptoms.
The research suggests that the ADGRE2 subunit interaction plays a key role in the mast cell response to certain physical stimuli, which could have implications for other diseases in which mast cells are involved. Next, the scientists plan to study what happens to the alpha subunit post-vibration and to unravel the cellular signaling leading to degranulation. They also plan to recruit more families with vibratory urticaria to further study the disorder and look for additional mutations in ADGRE2 and other genes.
NIAID conducts and supports research--at NIH, throughout the United States, and worldwide--to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
NHGRI is one of the 27 institutes and centers at the National Institutes of Health. The NHGRI Extramural Research Program supports grants for research and training and career development at sites nationwide. Additional information about NHGRI can be found at http://www.genome.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.NIH...Turning Discovery Into Health®
Reference: SE Boyden et al. Vibratory urticaria associated with a missense variant in ADGRE2. New England Journal of Medicine DOI: 10.1056/NEJMoa1500611 (2016).
NIH/National Institute of Allergy and Infectious Diseases
Related Family Articles:
The power of friendship gets stronger with age and may even be more important than family relationships, indicates new research by a Michigan State University scholar.
For 20 years, researchers have tried to find out why the chaperone Ssb is the only member of the widespread Hsp70-chaperone family that is able to bind directly to the ribosome.
How can couples and families effectively navigate issues such as divorce, teen parenting, or job loss?
Physicists in the College of Arts and Sciences have made science history by confirming the existence of a rare four-quark particle and discovering evidence of three other 'exotic' siblings.
Getting out in nature, even for just a 20-minute walk, can go a long way toward restoring your attention.
It's happened to many of us: While looking at someone you know very well, you blurt out the wrong name.
Family planning is a major health issue in India, the world's second most populous country.
By combining sophisticated RNA sequencing technology with a new device that isolates single cells and their progeny, MIT researchers can now trace detailed family histories for several generations of cells descended from one 'ancestor.'
Anthropologists study the Tsimane people of Bolivia to determine how parasitism affects female fertility.
Murderers who kill intimate partners and family members have a significantly different psychological and forensic profile from murderers who kill people they don't know, reports a new study.
Related Family Reading:
The Family: A Christian Perspective on the Contemporary Home
by Jack O. Balswick (Author), Judith K. Balswick (Author)
Two respected senior professors in the marriage and family field cover every issue that affects family life, including marriage, parenting, sexuality, communication, social dynamics, and family life in modern society. This proven resource for studying the most established of human institutions has been in print for over twenty years, with over 80,000 copies sold. The fourth edition has been updated to address current family-related issues and refined to reflect teaching practices for the contemporary classroom, including updated references to online resources.
Praise for a Previous... View Details
by J. California Cooper (Author)
In this wise, beguiling, and beautiful novel set in the era of the Civil War, award-winning playwright and author J. California Cooper paints a haunting portrait of a woman named Always and four generations of her African-American family. View Details
by Pa Chin (Author), Olga Lang (Introduction)
An essential work for anyone interested in the society and history of modern China! The first half of the twentieth century was a period of great turmoil in China. Family, one of the most popular Chinese novels of that time, vividly reflects that turmoil and serves as a basis for understanding what followed. Written in 1931, Family has been compared to Dream of the Red Chamber for its superb portrayal of the family life and society of its time. Drawn largely from Pa Chin's own experience, Family is the story of the Kao family compound, consisting of four... View Details
The Tech-Wise Family: Everyday Steps for Putting Technology in Its Proper Place
by Andy Crouch (Author), Amy Crouch (Foreword)
Making conscientious choices about technology in our families is more than just using internet filters and determining screen time limits for our children. It's about developing wisdom, character, and courage in the way we use digital media rather than accepting technology's promises of ease, instant gratification, and the world's knowledge at our fingertips. And it's definitely not just about the kids.
Drawing on in-depth original research from the Barna Group, Andy Crouch shows readers that the choices we make about technology have consequences we may never have considered. He takes... View Details
Marriages and Families (8th Edition)
by Nijole V. Benokraitis (Author)
ALERT: Before you purchase, check with your instructor or review your course syllabus to ensure that you select the correct ISBN. Several versions of Pearson's MyLab & Mastering products exist for each title, including customized versions for individual schools, and registrations are not transferable. In addition, you may need a CourseID, provided by your instructor, to register for and use Pearson's MyLab & Mastering products.
Celebrate diversity with a picture book for very young children about the many faces of contemporary families. Big or small, similar or different-looking, there are all kinds of families. Some have on parent, some have two, and many include extended family. This inclusive look at many varieties of families will help young readers see beyond their own immediate experiences and begin to understand others.View Details
Downsizing The Family Home: What to Save, What to Let Go (Downsizing the Home)
by Marni Jameson (Author), Mark Brunetz (Foreword)
“This is essential reading for anyone clearing out your own or a loved one’s home. . . . invaluable.” —The Wall Street Journal
It’s a rite of passage almost no one will escape: the difficult, emotional journey of downsizing your or your aging parents' home. Here, nationally syndicated home columnist Marni Jameson sensitively guides readers through the process, from opening that first closet, to sorting through a lifetime's worth of possessions, to selling the homestead itself. Using her own personal journey as a basis, she helps you figure out a strategy... View Details
The Family: Three Journeys into the Heart of the Twentieth Century
by David Laskin (Author)
The author of the The Children’s Blizzard delivers an epic work of twentieth century history through the riveting story of one extraordinary Jewish family
In tracing the roots of this family—his own family—Laskin captures the epic sweep of the twentieth century. A modern-day scribe, Laskin honors the traditions, the lives, and the choices of his ancestors: revolutionaries and entrepreneurs, scholars and farmers, tycoons and truck drivers. The Family is a deeply personal, dramatic, and emotional account of people caught in a cataclysmic time in world... View Details
Families, Families, Families!
by Suzanne Lang (Author), Max Lang (Illustrator)
No matter your size, shape, or pedigree--if you love each other, you are a family!
Moms, dads, sisters, brothers — and even Great Aunt Sue — appear in dozens of combinations, demonstrating all kinds of nontraditional families! Silly animals are cleverly depicted in framed portraits, and offer a warm celebration of family love.
From School Library Journal
PreS-Gr 1—Imagine a house with many rooms, whose walls each have a different color or wallpaper, accenting a family portrait hanging there. On a rustic wooden wall hangs the first portrait—a large family of ducks... View Details
Family Nurse Practitioner Certification Intensive Review, Third Edition: Fast Facts and Practice Questions (Book + App)
by Maria T. Codina Leik MSN ARNP FNP-C AGPCNP-BC (Author)
Now with a free mobile & web app with print purchase!
Doody’s Medical Review: 100 Points; 5 Stars (First Edition)
The third edition of this highly acclaimed review continues to promote efficient, time-saving study by synthesizing the complex knowledge needed to pass the exam into a concise, well-organized format. It is updated with key information about the new ANCC and AANPCB certification exams, including new test format questions featuring photos of skin and eye conditions and EKGs, and more challenging drag and-drop and... View Details