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Immunobiology

Significant Accomplishments

Insights into the Pathogenesis of Severe Asthma

The Division of Immunobiology has made significant strides toward its mission to elucidate the underlying mechanisms of immune-related diseases in children. These insights bring us closer to development of novel therapies for the treatment of childhood diseases. In particular, asthma is the leading cause of hospitalization in children. Although existing therapies effectively control mild forms of asthma, severe disease is not controlled by currently available therapies. Marsha Wills-Karp, PhD, and colleagues have identified a novel pathway by which severe asthma may develop. Specifically, they showed that overproduction of an innate immune mediator, complement factor C3, leads to aberrant Th17 cell responses, which induce severe asthma. This recognition may lead to the development of novel therapies for difficult-to-treat asthma (Lajoie, Nat. Immunol., 2010).

Mechanisms of Anemia in Children

Unexplained anemia and other low-blood counts are often found in patients who develop sudden and severe inflammation. Patients with these conditions, such as sepsis, can also look quite similar to children with a unique inborn immune disorder called hemophagocytic lymphohistiocytosis (HLH). Michael B. Jordan, MD, and his colleagues have found that a particular inflammatory molecule, interferon gamma (IFN-γ), which is found in excess in children with HLH, is a critical driver of the acute anemia observed during diverse microbial infections via a unique mechanism called hemophagocytosis (Zoller, JEM, 2011). In a related study, Jordan opened and expanded a multicenter clinical trial, called “Hybrid Immunotherapy for Hemophagocytic Lymphohistiocytosis” (HIT-HLH), which tests the idea that a unique combination of therapies that arrest damaging immune responses in this disorder may improve current treatments. As significant numbers of HLH patients die during the initial phases of therapy, this approach should improve survival of children with HLH.

Potential Novel Treatment for Fatal Food Allergies

Fatal anaphylactic responses have been associated with ingestion of certain foods such as peanuts in allergic individuals. Fred Finkelman, MD, and his colleagues have recently demonstrated that the production of IgG antibodies, rather than IgE antibodies, to food allergens is protective and that delivery of IgG antibodies systemically can suppress the induction of shock by food allergens (JACI, 2011). Moreover, they have identified new markers that can be used to distinguish whether an individual develops a deleterious IgE or protective IgG antibody response. Identification of the underlying antibody response may lead to the development of more specific therapies to prevent fatal anaphylactic responses in children (Khodoun et al., PNAS, 2011).