Regulation of the host immune system by helminth parasites

They may be called parasites, but we may owe helminth worms a great deal of appreciation.  At least, that’s what Dr Maizels and McSorley write in this month’s issue of the Journal of Allergy and Clinical Immunology (J Allergy Clin Immunol 2016; 138(3): 666-675).  To those who are unaware, there are only about a dozen or so species of helminths that commonly infect human beings, but they affect more than 2 billion people worldwide.  Their wide prevalence is a testament to the fact that they can evade host defenses and establish niches from themselves within our bodies.  Learning about how they do this can provide valuable insights about how our immune system works.

They do this through many different ways.  T-cells from helminth-infected asymptomatic humans show an increase in IL-4, IL-10, and TGF-beta over IL-17 and Interferon-gamma, suggesting that parasites skew our T-cells in a way that reduces the immune system’s ability to clear helminths.  In particular, the production of IL-10 correlates with the proliferation of regulatory T-cells, which in turn drive the body to produce IgG4 instead of pro-allergic IgE antibodies.  Interestingly, when helminths are cleared away by drug treatment, IgG4 levels decrease, which suggests that it is the helminths that are driving this movement.  Very broadly, this affects a host of other cells within the body, including macrophages, dendritic cells, and B-cells, which also seem to become more tolerating of these helminths.

The end-result of these changes is a mixed bag.  Helminths prevent the body from creating polyclonal responses, leading to decreased defense against pathogens like mycobacterium tuberculosis, and compromising the effect of childhood vaccines.  They also increase the risk of developing cancer, change metabolic processes (and maybe even protect against diseases like diabetes mellitus), and alter the bacteria that make up our gut microbiome.  Not surprisingly, at least in mice, helminth infection attenuates allergic responses as well. 

These insights are incredibly important, not only because they allow us to understand the immune system in a clearer manner, but also because research in this area holds the promise of creating new therapies that mimic the parasite molecules to treat a number of inflammatory diseases.

Creation and implementation of SAMPRO™: A school-based asthma management program

Childhood asthma affects over 6 million children in the United States.  In addition to its effects on physical health, asthma has an impact on academic and personal development.  Asthma related absences lead to decreased reading proficiency and increased learning disabilities.  In this month’s issue of the Journal of Allergy and Clinical Immunology, Lemanske and colleagues describe the creation of a central resource, termed SAMPRO (School-based Asthma Management Program). (J Allergy Clin Immunol 2016; 138(3): 711-723).

The SAMPRO workforce identified four components for development and implementation: (1) a circle of support facilitating communication, (2) asthma management plans, (3) comprehensive education plan, and (4) assessment of school environment. 

The circle of support is comprised of persons involved in taking care of children, including family, school personnel, clinicians, and community members.  School nurses in particular are pivotal in helping to ensure that children with asthma receive proper treatment.  In fact, the SAMPRO workforce strongly endorses full-time licensed registered nurses in schools (REF).

Secondly, the SAMPRO workforce strongly endorses the dissemination of asthma action plans among members of the circle of support.  Because asthma action plans have been shown to reduce deaths and emergency room visits, this is a high priority.  Electronic health information exchanges, web portals and continuity of care documents are methods that can help with this.

Thirdly, education of members within the circle of support has been highlighted, especially for school nurses.  The SAMPRO toolbox provides resources that can support nurses and others in managing chronic diseases in children.

Lastly, environmental triggers like pests, and poor indoor air quality have to be addressed.  55% of school districts require monthly campus-wide pest inspections but there remains a lot to be done.  The SAMPRO workforce recommends development of an Indoor Air Quality (IAQ) management program to help promote a healthy school environment. School staff needs to be educated in order to help empower them to make changes to the environment.

Altogether, these recommendations can help keep asthma from getting out of control enusring that children can continue to be at school, learning and growing rather than struggling with their breathing problems.

Clinical trial data access: Opening doors with TrialShare

The issue of “Data Sharing” has received considerable coverage in the medical literature and in the lay press recently.  There is a push to increase data transparency and to open such data for secondary use and analysis.  There have been different approaches to this issue with varying degrees of access. .  In this month’s issue of the Journal of Allergy and Clinical Immunology, Asare and colleagues describe their experiences with TrialShare, an online research resource providing data from the Immune Tolerance Network (ITN) of the National Institute for Allergy and Infectious Diseases (NIAID) (J Allergy Clin Immunol 2016; 138(3): 724-726).

Users of TrialShare have access to clinical trial protocols, case report forms, complete trial results, extensive de-identified participant level data, downloadable datasets for offline use, the ability to create alternate analyses, and a searchable database of ITN bio-specimen repository, among other features. 

The only requirement for registration is an e-mail address and password to establish an account.  In the 24 months since its introduction, a variety of different academic, government, nonprofit, and corporate individuals have used it to view and analyze data.

There are still many barriers preventing widespread use of data sharing software, but TrialShare is working towards breaking these down.  Unlike other data sharing projects, like the Yale Open Data Access Project and the Clinical Studies Data Access Project, there are no negotiation of data-use agreements and provisions to protect the competitive advantage of primary data generators.  Although there have been concerns that by sharing information more freely, there may be potential improper use of data, the experience of TrialShare has not demonstrated this.  And there is a vast infrastructure in the background to ensure that costs do not become burdensome for those carrying out clinical trials (about 0.5 to 2% of total costs of a clinical trial).

TrialShare is open to the biomedical community. Asare and colleagues invite us all to utilize this vital tool in order to ensure that the data being generated from immunology-related clinical trials is being analyzed in a free and open manner.