Immunology
Accurate interpretation of antinuclear antibodies test key to confirming autoimmune disease
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The presence of antinuclear antibodies (ANA) indicates the possibility of autoimmunity and the indirect immunofluorescence (IIF) assay on HEp-2 cells is the standard blood test (ANA-HEp-2) used to detect ANA. However, studies have shown that a “false-positive” ANA test occurs in up to 13% of healthy individuals. In such cases the test detects the presence of autoantibodies that apparently are not associated with autoimmunity. Researchers from Brazil have now uncovered distinguishing characteristics of the ANA test in healthy individuals and patients with autoimmune disease, reducing the likelihood of an erroneous autoimmune disorder diagnosis. Their findings are published in the January 2011 issue of Arthritis & Rheumatism, a journal of the American College of Rheumatology (ACR).
The immune system is responsible for protecting the body against foreign invaders and infection, but in some individuals the immune system repeatedly attacks healthy cells in the body resulting in an autoimmune disease. According to the Centers for Disease Control and Prevention (CDC) autoimmune diseases - which include rheumatoid arthritis, Sjögren’s syndrome, and systemic lupus erythematosus - affect up to 8% (22 million individuals) of the U.S. population.
The Brazilian research team, led by Luis Andrade, MD, PhD, from the Federal University of São Paulo, recruited 918 healthy individuals (634 females and 284 males) between the ages of 18 and 66 years for this study. In the control group were 153 patients with autoimmune rheumatic diseases that included lupus (87), systemic sclerosis (45), Sjögren’s syndrome (11) and idiopathic inflammatory myopathy (10). To determine the concentration of ANA in the blood, ANA-HEp-2 tests were run on all participants and considered positive if a well defined IIF pattern was identified.
Structure of Key Molecule in Immune System Provides Clues for Designing Drugs, According to Penn Study
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PHILADELPHIA - A team from the University of Pennsylvania School of Medicine and Utrecht University has deciphered a key step in an evolutionarily old branch of the immune response. This system, called complement, comprises a network of proteins that “complement” the work of antibodies in destroying foreign invaders. It serves as a rapid defense mechanism in most species from primitive sponges to humans.
In a study published in the December 24 issue of Science, the groups of John Lambris, PhD, the Dr. Ralph and Sally Weaver Professor of Research Medicine at Penn, and Piet Gros at Utrecht, detail the atomic structure of two key transient enzyme complexes in the human complement system.
Complement proteins mark both bacterial and dying host cells for elimination by the body’s cellular cleanup services and have been implicated in at least 30 diseases, including stroke, myocardial infarction, and age-related macular degeneration. The findings, Lambris says, provide a molecular scaffold for designing novel drug therapeutics.
Vaccine boosts your immune system
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Researchers at BRIC, the University of Copenhagen, have discovered that the human body can create its own vaccine, which boosts the immune system and helps prevent chronic inflammatory diseases. The researchers’ results have just been published in the prestigious Journal of Clinical Investigation and may have significant consequences in developing new medicine.
Researchers at the Biotech Research and Innovation Centre (BRIC) at the University of Copenhagen have discovered a protein normally found in the body that can act to prevent chronic tissue inflammation. When administered in the form of a therapeutic vaccine it is able to effectively prevent and treat a number of different inflammatory disease models for multiple sclerosis (MS), rheumatoid arthritis (RA), skin hypersensitivity and allergic asthma (AA).
The results of this study have just been published by the prestigious Journal of Clinical Investigation in the article entitled “Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates multiple tissue-specific inflammation in mice”.
Lower back and foot pain associated with more severe knee osteoarthritis symptoms
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A new study found that patients with osteoarthritis (OA) of the knee who also have pain in other joints were more likely to experience greater knee pain. Specifically, pain in the lower back as well as foot pain and elbow pain on the same side as the affected knee were associated with more severe knee pain. Full details appear in the December issue of Arthritis Care & Research, a journal published by Wiley-Blackwell on behalf of the American College of Rheumatology.
Knee OA is the leading cause of disability in the U.S., with nearly 4.3 million adults over age 60 having the symptomatic form of the disease according to the Centers for Disease Control and Prevention (CDC). A study by Helmick et al. published in Arthritis & Rheumatism reported 59 million people have low back pain, which is the most common cause of lost work time among individuals less than 45 years of age and the third most common cause among those 45 to 65 years of age.
The current study team led by Pradeep Suri, M.D., from Harvard Medical School, New England Baptist Hospital, and Spaulding Rehabilitation Hospital in Boston, Massachusetts used data provided by individuals from the Osteoarthritis Initiative - a multicenter population-based observational cohort study of knee OA.
Pregnancy outcome affected by immune system genes
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A team of researchers, led by Ashley Moffett, at the University of Cambridge, United Kingdom, has shed new light on genetic factors that increase susceptibility to and provide protection from common disorders of pregnancy, specifically recurrent miscarriage, preeclampsia, and fetal growth restriction.
A key step in the initiation of a successful pregnancy is the invasion of the lining of the uterus by fetal cells known as trophoblasts, which become the main cell type of the placenta. Recurrent miscarriage, preeclampsia, and fetal growth restriction are thought to result from inadequate trophoblast invasion of the uterus lining. Interactions between maternal cells known as uterine NK cells and fetal trophoblasts — specifically interactions between HLA-C molecules on the fetal trophoblasts and KIRs on the maternal uterine NK cells — are key to determining the extent of trophoblast invasion. Previous data from Moffett’s lab indicated that a particular combination of fetal HLA-C and maternal KIR was associated with increased risk of preeclampsia. In this study, the team has extended this correlation to recurrent miscarriage and fetal growth restriction. Furthermore, they have determined that the presence of other maternal KIRs that combine with the same HLA-C molecule provides protection against the same common disorders of pregnancy.
Major disease-vector mosquito reveals the secrets of its immune system
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The Culex quinquefasciatus mosquito poses a significant threat to human health as a blood-sucking transmitter of elephantiasis-causing worms and encephalitis-inducing viruses. An international team of scientists, including researchers from the University of Geneva and the SIB Swiss Institute of Bioinformatics sequenced its genome and studied its responses to pathogen infections. Two articles published in today’s issue of Science, describe results from comparing the Culex mosquito with the malaria mosquito, Anopheles gambiae, and the dengue mosquito, Aedes aegypti, which offer new insights into the elimination of insect-transmitted diseases that seriously impact on global public health.
Mosquitoes are the most important disease-vectors. Species of Culex, Aedes, and Anopheles mosquitoes are responsible for the transmission of many human pathogens including parasites that cause malaria, viruses that trigger dengue and yellow fever, and West Nile encephalitis, as well as worms that cause lymphatic filariasis (also called elephantiasis). The capacity of different mosquito species to transmit these and other pathogens varies greatly, and much of this variation can be attributed to the mosquito immune system’s ability to recognise and eliminate the pathogen. Applying their expertise in comparative evolutionary genomic analyses and insect immunity, Professor Evgeny Zdobnov and Dr Robert Waterhouse, from the University of Geneva Medical School and the SIB Swiss Institute of Bioinformatics, joined forces with scientists from around the world to examine the Culex genome and its encoded genes.
Sequencing of the Culex genome, directed by Peter Atkinson and Peter Arensburger from the University of California Riverside, allowed researchers to perform a thorough comparison among the three disease-vector mosquito species.
Improving Endpoints for Cancer Immunotherapy Clinical Trials
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The Cancer Research Institute (CRI) Cancer Immunotherapy Consortium (CIC), the leading global initiative in advancing the emerging field of immuno-oncology, has proposed criteria for improved endpoints for cancer immunotherapy trials, which were published online on September 8 in the Journal of the National Cancer Institute.
These improved clinical trial endpoints help to distinguish between the effects of chemotherapy and immunotherapy and address long-needed adjustments of standard endpoints such as survival and anti-tumor response. In addition, they introduce harmonization criteria for immune response assays to help establish immune response as a biomarker in clinical trials.
Over the last six years, the CIC has worked across the community of scientists involved with cancer immunotherapy within academia, industry, and regulatory agencies, and has developed these trial endpoint recommendations based on consensus workshops and clinical and laboratory data.
Early-Life Exposure to Polychlorinated Biphenyls Reduces Immune Response to Vaccination
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Children exposed to polychlorinated biphenyls (PCBs) early in life later had a diminished immune response to diphtheria and tetanus vaccinations, according to a study published online June 20 ahead of print in the peer-reviewed journal Environmental Health Perspectives (EHP). This result suggests that PCB exposure during the first years of life, a critical period in immune system development, could undermine the effectiveness of childhood vaccinations and possibly impair immune system responses to infection.
PCBs are long-lived environmental contaminants that are suspected to be toxic to the immune system. The study included 587 children born between 1999 and 2001 who lived in the Faroe Islands. The residents of the Faroe Islands, which lie midway between Norway and Iceland in the North Atlantic, have widely varying PCB exposure due to differing consumption patterns of contaminated traditional foods such as pilot whale blubber. Routine childhood vaccinations, which feature standard antigen doses at set time points, provided an opportunity to examine immune responses in the Faroese children.
Mothers provided blood samples at 32 weeks of pregnancy and milk samples 4 to 5 days after birth.
Eliminating the source of asthma-causing immune molecules
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Asthma and other allergic diseases are caused by inappropriate immune responses. Soluble IgE molecules, produced by immune cells known as B cells, are key immune mediators of these diseases. Therapeutic targeting of IgE in the blood can neutralize its effects and is an effective treatment for moderate-to-severe allergic asthma.
However, this approach does not halt IgE production and patients need to be treated repeatedly. But now, a team of researchers, at Genentech Inc., South San Francisco, has developed a way to specifically eliminate IgE-producing B cells, providing a potential new long-lasting therapeutic approach to treating asthma and other allergic diseases.
IgE-producing B cells express on their surface an IgE molecule that is slightly different to the IgE molecules that they secrete. The team, led by Lawren Wu, generated a therapeutic molecule known as a monoclonal antibody that targets the portion of human IgE that is contained in IgE molecules on the surface of B cells but not in IgE molecules in the blood.
Faithful mothers have healthier babies
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Faculty of 1000 reviewers examine a study from New Zealand on whether prolonged exposure to the father’s semen protects new mothers against pre-eclampsia and having an undersized baby
In this study by Kho and colleagues at the University of Auckland, published in the Journal of Reproductive Immunology, 2507 first-time pregnant women were interviewed about the length of their relationship with the baby’s biological father.
When the pregnancies came to term, pre-eclampsia (pregnancy-induced hypertension) was found to be less common in women who had long-term sexual relations exclusively with the biological father, than in those who had been with their partner only for a short time (i.e. less than six months).
US group advises cuts in post-exposure rabies jabs
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U.S. immunization advisers have recommended reducing the number of rabies shots needed to protect humans after exposure to a rabid animal in a move to conserve vaccine supplies.
The Advisory Committee on Immunization Practices or ACIP, which advises the U.S. Centers for Disease Control and Prevention, voted on Wednesday to change the vaccine schedule from five doses to four, eliminating the last shot.
The move was intended to conserve vaccine supplies in the event of a vaccine shortage, which occurred from 2007 to 2009.
New Therapy Enlists Immune System to Boost Cure Rate in a Childhood Cancer
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A multicenter research team has announced encouraging results for an experimental therapy using elements of the body’s immune system to improve cure rates for children with neuroblastoma, a challenging cancer of the nervous system.
John M. Maris, M.D., chief of Oncology at The Children’s Hospital of Philadelphia, co-authored the phase 3 clinical trial, which was led by Alice Yu, M.D., Ph.D., of the University of California, San Diego. Maris chairs the committee supervising the trial for the Children’s Oncology Group, a cooperative organization that pools resources from leading medical centers to study and devise new treatments for pediatric cancers.
Neuroblastoma, a cancer of the peripheral nervous system, usually appears as a solid tumor in the chest or abdomen. Neuroblastoma accounts for 7 percent of all childhood cancers, but due to its often aggressive nature, causes 15 percent of all childhood cancer deaths.
Scientists Discover How to Improve Immune Response to Cancer
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A team of scientists at The Campbell Family Institute for Breast Cancer Research (CFIBCR) at Princess Margaret Hospital and international collaborators have discovered how to trigger an improved immune response to cancer that could be included in new clinical trials that use a patient’s own cells to destroy tumours.
The findings, published online today in Nature Medicine (DOI: 10.1038/nm.1953), demonstrate the tantalizing potential of immunotherapy in cancer treatment, says principal investigator Dr. Pamela Ohashi, co-director, CFIBCR.
In the lab study, the scientists combined interleukin-7 (IL-7) – a key component of the immune system – with a viral vaccine to improve the ability of the cells of the immune system to attack tumours. The result was clear: The combination boosted immunity to tumours.
A potential marker of increased histological activity in hepatitis C virus infection
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Early, vigorous and sustained lymphocyte proliferative responses specific to hepatitis C virus (HCV) have been regarded as pivotal for viral clearance. On the other hand, antibody responses’ contribution is still controversial. Research data have been accumulated regarding the significance of specific antibody classes during chronic infection. Particularly, the relation of IgA and alcohol-induced hepatic damage has been recognized, but its possible implication in HCV chronic infection has not been explored so far.
A research article to be published on November 28, 2008 in the World Journal of Gastroenterology addresses this question. This article investigated the HCV-specific immune responses in chronic treated and untreated patients, in paired samples taken 6 months apart. IgG, IgM and IgA levels, as well as IgG1-4 subclasses and peripheral blood lymphocyte proliferative responses against core, envelope and NS3 antigens were assayed by ELISA and CFSE staining, respectively.
Over 70% of the patients showed specific IgG and IgM against HCV capsid, E1 and NS3, while the hypervariable region-1 of E2 was recognized by half of patients. Anti-capsid IgM and IgG levels increased over time, while IgA levels did not; instead, an increase in IgA positive samples was observed.
Oral immunotherapy promising for children with milk allergy
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Oral immunotherapy for cow’s milk allergy appears to effectively desensitize allergic children, a new study indicates, although further work is needed to determine the best dosing, duration of therapy, and whether permanent tolerance can be achieved, the study team emphasizes.
Twenty children, 6 to 17 years of age, with a known history of milk allergy were randomly assigned to placebo or to milk in a three-phase dosing schedule. On the first day, a dose of 0.4 mg milk protein was administered, and escalated about every 30 minutes to a maximum first-day dose of 50 mg.
Home dosing was then initiated at the highest tolerated dosage, followed by 8 weekly in-office dose increases to a maximum of 500 mg. Once a dose of 500 mg (equivalent to 15 mL of milk) was achieved, participants remained on this daily maintenance dose for 13 weeks.
