Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Defective gene linked to two inherited immune deficiencies

08.08.2005


Defects in a single gene can result in two immune system disorders that leave affected individuals vulnerable to frequent or unusually severe infections, according to new findings reported in the August issue of Nature Genetics. The discovery may lead to new diagnostic tests for these two inherited conditions--immunoglobulin A (IgA) deficiency and common variable immunodeficiency (CVID) Currently, doctors diagnose the conditions by measuring immunoglobulin levels and excluding other causes for lowered immunoglobulin levels; there are no specific tests to detect the two disorders.

A deficiency of IgA--an important type of infection-fighting antibody found in tears, saliva and other secretions--affects 1 in 600 people in the western world; CVID is less common but more severe. Both conditions result in a person being more susceptible to pneumonia and to recurring infections of the ear, sinus and gastrointestinal tract. People with CVID also have an increased risk of developing cancers that affect B cells, cells that produce antibodies. Furthermore, IgA deficiency and CVID can predispose to autoimmune diseases, where the immune system turns against the body’s own tissues and organs.

"Most cases of CVID and IgA deficiency are of unknown cause," notes Josiah Wedgwood, M.D., Ph.D., of the Clinical Immunology Branch of the National Institute of Allergy and Infectious Diseases (NIAID), the component of the National Institutes of Health that funded the study. "To find a specific molecular defect that is the apparent cause of illness in a substantial subset of individuals with these two diseases is extremely important. Not only will this finding enable us to better diagnose these patients, it provides clues to key biochemical pathways that can lead to immunodeficiencies."



The study was led by Raif Geha, M.D., and Emanuela Castigli, Ph.D., of the Children’s Hospital Boston. The Boston team found specific mutations in a gene known as TACI, which plays a specific role in orchestrating the immune response. Defects in TACI were found in 4 of 19 unrelated patients with CVID and in 1 of 16 unrelated patients with IgA deficiency. None of 50 healthy people they studied had a TACI mutation. The scientists believe that it is likely that as yet unidentified genetic defects underlie CVID and IgA deficiency in those cases where TACI was not mutated.

When the scientists further examined four of the five individuals with TACI mutations, they found all four had relatives with the same mutations. Eleven of the 12 identified relatives with CVID or IgA deficiency reported a history of recurrent infections and were also found to have low levels of IgA and/or low levels of another type of antibody, immunoglobulin G (IgG).

TACI mutations interfere with two aspects of the immune response that involve maturation of B cells. Normally, TACI triggers B cells to switch from making immunoglobulin M (IgM), an antibody produced early in the immune response, to making other antibodies such as IgA and IgG. More important, TACI signals B cells to produce antibodies against specific invading bacteria and viruses.

Because TACI mutations are genetically dominant, a person with TACI mutations in one of the two TACI genes he or she inherits is unable to mount a strong antibody response. Each child of a person so affected has a fifty percent chance of inheriting the mutation and being predisposed to IgA deficiency and CVID.

"A test for TACI defects would enable the diagnosis of more children and their relatives with these immune deficiencies," says Dr. Geha, senior author of the study and the James Gamble Professor of Pediatrics at Harvard Medical School. "Many children who are sick with these disorders are now missed, because they can have normal IgA and IgG levels, yet they still have poor antibody responses and get the same bacterial and virus infections again and again."

But the gene discovery will not immediately change treatment strategies, notes Dr. Geha. "For the time being, therapy still consists of prophylactic antibiotics or intravenous immunoglobulin infusions every three weeks," he says.

NIAID News Office | EurekAlert!
Further information:
http://www.nih.gov

More articles from Life Sciences:

nachricht Study shines light on brain cells that coordinate movement
26.06.2017 | University of Washington Health Sciences/UW Medicine

nachricht New insight into a central biological dogma on ion transport
26.06.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Study shines light on brain cells that coordinate movement

26.06.2017 | Life Sciences

Smooth propagation of spin waves using gold

26.06.2017 | Physics and Astronomy

Switchable DNA mini-machines store information

26.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>