Volume 129, Issue 2 , Pages 273-274, February 2012
News Beyond Our Pages
Article Outline
- Improved clinical outcomes with reslizumab in a subpopulation of patients with eosinophilic asthma
- A possible cure for the “common cold”?
- Human low-affinity IgG receptor (FcγRIIA) sufficient for anaphylaxis
- Atopy linked to lymphoid stress surveillance responses
- Intermittent budesonide therapy for children with recurrent wheezing
Improved clinical outcomes with reslizumab in a subpopulation of patients with eosinophilic asthma
Previous research on reslizumab, an anti–IL-5 mAb, in asthmatic patients did not provide a clear clinical benefit; however, improvements were noted in small studies in subgroups of patients with eosinophilic asthma. Castro et al (Am J Respir Crit Care Med 2011;184:1125-32) investigated reslizumab's effectiveness in 106 patients with uncontrolled asthma with eosinophilia exclusively. The primary outcome (asthma control questionnaire) was not significantly improved. However, the authors found that airway function improved and sputum and blood eosinophilia decreased in the reslizumab-treated group. Moreover, they reported a novel finding. Patients with nasal polyposis had a statistically significant improvement in asthma control compared with those without polyposis. Thus there might be a subpopulation of patients with eosinophilic asthma whose symptoms can be controlled with anti–IL-5 consistent with other recent reports concerning another anti-IL-5 therapeutic.
Lead author, Mario Castro, MD, at Washington University, St Louis, Mo, gave us this comment on their findings: “The results of this trial add to the growing body of evidence that there are sub-phenotypes of severe asthma that can be identified by combining clinical history with biomarkers, such as sputum eosinophils, to provide targeted therapy. These subgroups now need to be prospectively tested in randomized controlled trials with novel therapies to test their effectiveness and safety.”
A possible cure for the “common cold”?
Rhinovirus, the most common agent of the “common cold,” is of great concern for patients with asthma or chronic obstructive pulmonary disease, being responsible for exacerbations and hospitalizations. An article by Niespodziana et al (FASEB J 2011, 10.1096/fj.11-193557) presented very interesting results from their investigation of mechanisms of memory immune responses during rhinovirus infections, which explained why acquired immunity to rhinovirus does not protect from recurrent infection. The authors reported that the major rhinovirus epitope that generated IgG1 and IgA responses was a nonneutralizing peptide found inside the viral capsid during viral binding. The authors suggested that this misdirection accounted for the failure of memory immunity to provide protection against future rhinovirus infection. They also noted that their findings would facilitate the development of vaccines against the rhinovirus epitopes that are responsible for infection.
Rudolf Valenta, MD, senior author, commented: “Based on the results of our work it may be possible to develop vaccines which allow to focus neutralizing antibodies against those rhinovirus capsid structures which are involved in docking to human cells and thus to prevent rhinovirus infections.”
Rudolf Valenta
Human low-affinity IgG receptor (FcγRIIA) sufficient for anaphylaxis
Following up on their results in mice in which they demonstrated that active and passive anaphylaxis was dependent on IgG and its receptors, FcγRIIIA and FcγRIV, expressed on neutrophils, Jönsson et al (Blood 2011, doi:10.1182/blood-2011-07-367334) reported results from anaphylaxis studies with transgenic mice that express the human low-affinity IgG receptor FcγRIIA. They showed that FcγRIIA was sufficient to induce fatal active anaphylaxis upon antigen challenge. Jönsson et al also demonstrated that FcγRIIA activation on mast cells mediated passive cutaneous anaphylaxis; however, FcγRIIA aggregation on monocytes and neutrophils was responsible for passive systemic anaphylaxis. Monoclonal antibody blockade of FcγRIIA abolished anaphylactic responses. The authors also showed that mast cells, monocytes, and neutrophils released anaphylactic mediators, such as histamine, platelet-activating factor and leukotrienes, after FcγRIIA binding. The possible applicability of these results to human subjects would have significant implications for eventually understanding and treating various forms of anaphylaxis.
Senior author, Pierre Bruhns, PhD, at INSERM, Paris, France, gave this statement: “Human FcgRIIA (CD32A) is the most widely expressed IgG receptor in humans, and it can activate all allergy-related cell types (mast cells, basophils, eosinophils, monocytes and neutrophils). The study performed by Friederike Jönsson, PhD, demonstrates that FcγRIIA can, in the absence of any other IgG receptor, recapitulate allergic inflammation and anaphylaxis when in presence of allergen-specific IgG and allergen. As evidence accumulates of circulating allergen-specific IgG in patients, the contribution of FcγRIIA and IgG should be re-evaluated in allergic diseases, particularly in anaphylaxis.”
Pierre Bruhns and Friederike Jönsson
Atopy linked to lymphoid stress surveillance responses
The presence of γδ T cells in tissue-resident T-cell compartments has been suggested to represent a stress surveillance system that is activated when epithelial damage occurs. This system is mediated through production of cytokines and ligands that bind to the natural killer cell receptor NKG2D. Recently, Strid et al (Science 2011;334:1293-7) reported that mild abrasive skin damage on mice resulted in local γδ T cell–associated NKG2D activation, as well as increased TH2 cytokine mRNA expression (eg, IL-1, IL-25, IL-33, and thymic stromal lymphopoietin). The authors also showed that antigen exposure concomitant with skin abrasion caused increased levels of antigen-specific IgE, IgG, and IgG1, supporting both local and systemic effects of the epithelial damage. Strid et al concluded that their findings support a requirement for γδ T cells, as part of the lymphoid stress surveillance system, to initiate TH2-dominant responses associated with the development of atopy when environmental molecules co-occur with epithelial damage.
Their findings support a requirement for γδ T cells, as part of the lymphoid stress surveillance system, to initiate TH2-dominant responses
Intermittent budesonide therapy for children with recurrent wheezing
Concerns over adherence and growth suppression in children with wheeze who are regularly treated with inhaled corticosteroids have prompted re-examination of some clinical guidelines by the National Heart, Lung, and Blood Institute's Childhood Asthma Research and Education Network. Zeiger et al (N Engl J Med 2011;365:1990-2001) compared low-dose, daily inhaled budesonide with intermittent budesonide therapy initiated at the beginning of respiratory tract infection and continued for 1 week in 278 children between the ages of 12 and 53 months with frequent, episodic wheezing at risk for asthma exacerbation. The authors found that daily low-dose budesonide therapy did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations. Although the difference in growth measures was not statistically significant between the 2 groups, they noted that the mean exposure to budesonide was greater in those undergoing the daily low-dose regimen. Zeiger et al commented that their findings of lack of superiority of daily low-dose budesonide to high-dose intermittent budesonide might be an important consideration in future clinical guidelines.
Lead author, Robert Zeiger, MD, PhD, at Kaiser Permanente and University of California, San Diego, gave us this comment: “Our study offers a treatment option for wheezing preschoolers. . .while the study may benefit many preschoolers who wheeze during respiratory illnesses, it did not evaluate children who have more severe disease or persistent symptoms. A critical element of the intermittent approach is that parents were trained on when to start the intermittent regimen so it was not used for every respiratory illness or symptom.”
Robert Zeiger
News items are written by Sherri Gabbert, PhD.
Find more News Beyond Our Pages online at www.jaci-nbop.blogspot.com.
PII: S0091-6749(11)02946-0
doi:10.1016/j.jaci.2011.12.977
Volume 129, Issue 2 , Pages 273-274, February 2012
