Some form of immunotherapy for individuals allergic to peanuts is likely to be available within the next 5 years, according to Professor Wesley Burks, a food allergy expert. This prediction, made in a Seminar published in the May issue of The Lancet, is likely to bring relief to many concerned parents of peanut allergy sufferers.
Peanut allergy affects approximately 1% of children under the age of 5 years and is a disease modulated by IgE. In sufferers, ingested peanut protein crosslinks with the IgE antibodies of the immune system, bringing about the release of inflammatory molecules such as histamine. The disease is an increasing health concern, especially in developed countries; in one study in the USA, the prevalence of peanut allergy in young children was shown to have doubled between 1997 and 2008 – from 0.4 to 0.8%.
Although it is not known why the prevalence of peanut allergy is rising, the so-called ‘hygiene hypothesis’ is one theory that has been proposed, which states that the increased susceptibility to allergies observed in the Western world is a consequence of a lack of exposure to infectious agents in early childhood.
In his recently published Seminar, Burks discussed a number of theories as to why the prevalence of peanut allergy is increasing, as well as various other issues, including how the condition is diagnosed and managed.
Importantly, Burks also examined the potential new treatments and prevention strategies currently under development for peanut allergy sufferers. Scientists across the world are working on the development of novel immunotherapeutic strategies, with future treatments aimed at either curbing the immune response or inducing immune tolerance to the antigens. Possible approaches include using engineered peanut proteins as immunotherapy and specific oral tolerance induction, whereby the allergen is ingested in increasingly larger amounts on a regular basis.
“These studies offer the possibility of at least raising the threshold of the amount of peanut that it would take to cause a life-threatening allergic reaction; whether these types of treatments are likely to cause eventual clinical tolerance to develop remains to be seen,” wrote Burks.
As the condition becomes increasingly common, it will become ever-more imperative to develop effective treatments. For this reason, Professor Burks’ conclusion in his Seminar that the next 5 years will likely see some form of immunotherapy for peanut allergenic individuals is certainly an encouraging one.
Source: Burks AW. Peanut allergy. Lancet 371(9623), 1538–1546 (2008).
Immune-modulating drugs may carry risks of serious infections
Drugs commonly prescribed to treat immunological conditions such as rheumatoid arthritis and inflammatory bowel disease may carry the risk of serious infections other than the known risk of tuberculosis (TB), according to the results of a new survey. These findings suggest that physicians should be vigilant not just for TB but for a range of different infections in patients taking these drugs.
Autoimmune diseases encompass a wide range of different diseases, all of which are a consequence of the immune system wrongly identifying self-antigens as foreign, resulting in an aberrant immune response against the body’s own cells and tissues. Prominent examples of autoimmune diseases include celiac disease, irritable bowel syndrome and rheumatoid arthritis.
Among the medications used to treat such disorders are drugs that curb the immune response through inhibiting the action of the proinflammatory cytokine TNF-α. It has already been established that these anti-TNF-α agents are associated with an increased risk of TB infection and, to date, much attention has been focused on cases of TB occurring in patients using these drugs.
A recently published article presented the results of a nationwide survey that was carried out in order to identify a range of serious infections in patients receiving anti-TNF-α compounds. In this survey, 426 infectious disease physicians, members of the Emerging Infections Network of the Infectious Diseases Society of America, reported on the infections they had observed within the previous 6 months. In this context, cases of Staphylococcus aureus, histoplasmosis and nontuberculosis mycobacterial infections were all reported more commonly than TB.
The results of this study suggest that patients using anti-TNF-α therapy might be at an increased risk of a number of serious infections and that physicians should be cautious of infections other than TB in individuals who are either currently using or initiating anti-TNF-α therapy.
Source: Winthrop KL, Yamashita S, Beekmann SE, Polgreen PM; Infectious Diseases Society of America Emerging Infections Network. Mycobacterial and other serious infections in patients receiving anti-tumor necrosis factor and other newly approved biologic therapies: case finding through the Emerging Infections Network. Clin. Infect. Dis. 46(11), 1738–1740 (2008).
New study to investigate the causes of Type 1 diabetes
Juvenile Diabetes Research Foundation (JDRF), the leading charitable funder of Type 1 diabetes research worldwide, has awarded over GB£3 million pounds to fund a study to investigate the causes of Type 1 diabetes. The study hopes to shed light on how and why the disease occurs so that novel therapies can be developed to treat the condition.
Type 1 diabetes is a serious and life-threatening autoimmune disease that results in the destruction of the insulin-producing cells of the pancreas. The consequent lack of insulin rapidly results in serious illness and, if left untreated, death. In order to remain alive, diabetics require multiple daily injections of insulin. Importantly, these injections are not a cure; they are merely a means by which diabetics can self-manage their blood sugar levels in light of not having an endogenous insulin supply.
Although there are ongoing clinical trials aimed at finding methods of preventing or slowing the development of Type 1 diabetes, none so far has proven successful.
The newly funded study, known as the JDRF Centre for Diabetes Genes, Autoimmunity and Prevention (D-GAP), will bring together some of the UK’s leading diabetes researchers, including professors from King’s College London, the University of Cambridge and the University of Bristol, in an attempt to unravel the relationship between genes, immunity and Type 1 diabetes.
Researchers will take genetic samples from over 4000 volunteers across the UK, comprised of Type 1 diabetics, their relatives and members of the general population. Having collected all the samples, researchers will carry out a series of measurements on the white blood cells, cells involved in the immune response. If a link between these white blood cell measurements and the genetic profile of the samples can be identified, it will shed light on the disease process of diabetes, paving the way for new drugs and therapies to be developed.
“A key part of JDRF’s research is aimed at stopping or reversing the immune system response that causes Type 1 diabetes and D-GAP could provide the answers needed to achieve that. If we are able to understand what causes Type 1 diabetes, we will be another step closer to finding the cure”, says Karen Addington, Chief Executive of JRDF in the UK.
Source: Juvenile Diabetes Research Foundation www.jdrf.org.uk
Efalizumab appears safe for long-term use in psoriasis patients
Drug name: Efalizumab
Trade name: Raptiva®
Indication: Moderate-to-severe chronic plaque psoriasis
A review of data based on 10 years of experience using efalizumab (Raptiva®) in patients with moderate-to-severe chronic plaque psoriasis has confirmed that the drug has a favorable long-term safety profile. The data are encouraging, providing support for the use of efalizumab as an appropriate long-term treatment option for sufferers of this life-long condition.
Psoriasis is a common chronic inflammatory skin condition, affecting approximately 2% of the UK population. The condition causes skin cells to grow abnormally, resulting in thick, red, inflamed, scaly patches of skin, most commonly on the knees, elbows, trunk and scalp.
The etiology of psoriasis is unknown and, although there are a number of medications available to help control the symptoms, there is, as yet, no cure. Patients with moderate-to-severe psoriasis require life-long treatment and there is currently a significant unmet clinical need for durable psoriasis therapies – drugs that can be safely used in the long term to effectively manage the disease.
Efalizumab is a humanized anti-CD11a monoclonal antibody that binds to and blocks the activity of CD11a on the surface of T cells, thereby inhibiting the T-cell-mediated processes involved in the pathogenesis of psoriasis.
In this recent review, data were gathered from over a decade of clinical experience and postmarketing surveillance of efalizumab and a safety review was carried out. The results demonstrated that efalizumab had a favorable safety profile, with no reported increase in adverse events.
Notably, resent research has shown that the chronic inflammation that causes the visible symptoms of psoriasis on the skin also significantly affects the organs beneath the skin. Psoriasis sufferers are at a significantly increased risk of comorbidities, such as obesity and diabetes, and the disease reduces life expectancy by up to 10 years.
In order to manage psoriasis more affectively and to control the associated systemic inflammation, the focus should be on treating patients earlier and more aggressively. Consequently, there is a real need for drugs that are well tolerated and associated with favorable long-term safety profiles. The findings of this recent safety data analysis are therefore encouraging for those afflicted with moderate-to-severe psoriasis, providing support for the long-term use of efalizumab in many of these patients.
Source: Medical News Today www.medicalnewstoday.com/articles/108598.php
Molecule made by gut bacteria may offer a new type of treatment for inflammatory bowel disease
A naturally occurring molecule produced by symbiotic bacteria living in the human gut may have the potential to be developed for use as a natural therapeutic for inflammatory bowel disease (IBD), according to researchers.
It is estimated that up to 1 million Americans have IBD, a term that encompasses a number of immune-mediated conditions that cause inflammation of the intestines, the two predominant diseases of which are Crohn’s disease and ulcerative colitis.
The human GI tract, the site of the body affected by IBD, is home to 100 trillion bacteria, some of which are potentially pathogenic and can be responsible for infection and acute disease. However, other gut bacteria can be beneficial, existing in a mutually beneficial ‘symbiotic’ relationship with their human host. It has been proposed that imbalances in the bacterial microbiota of our gut could be a key factor in the pathogenesis of IBD.
In a recent study led by Sarkis Mazmanian, scientists exposed laboratory mice to the pathogenic bacterium Helicobacter hepaticus in order to upset the intestinal microbiota and induce a disease in the mice that resembles human Crohn’s disease and ulcerative colitis. The team then co-colonized the mice with the prominent human symbiont Bacteriodes fragilis and found that the mice were protected from disease. Furthermore, the researchers were able to identify a single molecule produced by B. fragilis that was responsible for the protective effects of this bacterium, a sugar known as polysaccharide A (PSA); mice given only oral doses of PSA were also protected from the experimentally induced colitis.
Notably, PSA was found to cause the CD4+ T cells of the immune system to release IL-10, a molecule with demonstrated anti-inflammatory properties that has previously been shown to offer protection against IBD. It seems that, through the production of PSA, B. fragilis is able to induce the production of IL-10, reprogramming the host’s immune system to reduce gut inflammation.
Significantly, it may be possible to harness the beneficial activities of PSA to treat aberrant gut inflammation: “The most immediate and obvious application is that PSA may potentially be developed as a natural therapeutic of inflammatory bowel disease,” says Mazmanian.
Moreover, Mazmanian’s team predict that there may be many other bacterial compounds with beneficial activities awaiting discovery. Through the production of these molecules, termed ‘symbiosis factors’ by Mazmanian and colleagues, numerous species of bacteria are able to positively interact with the immune system of their host in order to actively promote the health of the individual in which they reside, thereby creating an enhanced environment for their own survival.
It is hoped that, on the basis of the immunomodulatory properties of these naturally occurring bacterial compounds, a number of these symbiosis factors may be developed into new therapeutics for the treatment of inflammatory disorders such as IBD.
Interestingly, this recent study also provides evidence to support the ‘hygeine hypothesis’, one theory that has been proposed to account for the recent and dramatic increase in the prevalence of certain diseases, such as asthma and allergies, in the Western world.
Similar to what has been observed for a number of illnesses in developed countries, the incidence of IBD has increased considerably in recent years; for example, over the past 20 years, the rate of Crohn’s disease has increased by 400%.
The hygiene hypothesis links the observed rise in prevalence of these diseases to modern practices that reduce bacterial infections, such as sanitation, vaccination and antibiotic use. Evidently, these antimicrobial practices do not only affect the infectious microbes for which they are intended, they also affect a number of beneficial bacteria on which our well-being may depend.
As demonstrated for IBD in this recent study, molecules produced by the bacterial microbiota can mediate the critical balance between health and disease. This study suggests that the interplay between the various different groups of bacteria living in our intestines has a profound effect on human health and, through our modern lifestyle and the implementation of antimicrobial practices, we may be upsetting the balance of our gut microbiota and, consequently, causing IBD. Therefore, although it is clearly important to protect ourselves against infection by eliminating potentially pathogenic bacteria, it may be the case that certain diseases also result from the absence of beneficial bacteria and their positive effects on our health.
Source: Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453(7195) 620–625 (2008).