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Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief and Guest Reviewer Gary Hellermann,
PhD, reviewed premier medical journal articles for practicing
1. Exhaled nitric oxide distinguishes between subgroups of
preschool children with respiratory symptoms.
The goal of the Tucson Children's Respiratory Study is to
identify the factors that predispose nonwheezing and wheezing
children less than four yrs to develop chronic lung disease.
Measurement of fractional exhaled nitric oxide (FeNO) is
suitable even for infants and is useful in predicting
exacerbations and monitoring therapy in older children. This
study of 391 children demonstrates that FeNO levels are highest
in children with frequent recurrent wheeze and a stringent index
for prediction of asthma at school years. Editor's Comment:
FeNO may be useful to predict asthma susceptibility later in
life. Moeller A et al.
J Allergy Clin Immunol 2008; 121:705. Bacharier LB,
391名の乳幼児について、下気道炎症を評価するための分画呼気NO, fractional exhaled nitric
2. Intrinsically defective skin barrier function in
children with atopic dermatitis (AD) correlates with disease
AD is a disease with multiple environmental and genetic factors.
Research implicates defects in the skin barrier layer as one
cause of the pathology. This study compares transepidermal water
loss (TEWL) in a group of African American and white children
with AD, children with asthma or allergic rhinitis but no AD,
and healthy controls. Increased TEWL correlates with a defective
skin barrier and AD severity using the SCORAD index. Editor's
Comment: TEWL may be a useful biomarker for AD severity, but
whether this skin barrier defect contributes to AD remains
unknown. Gupta J et al.
J Allergy Clin Immunol 2008; 121:725.
2b. Impaired Th17 cell differentiation in subjects with
autosomal dominant hyper-IgE syndrome (HIES).
HIES is a serious disease that impairs the immune system's
ability to fight off infections and is associated with atopic
dermatitis and abnormalities of bone and connective tissue.
Mutations in the signal transducer and activator of
transcription 3 (STAT3) are present in some HIES patients. This
clinical study looks at healthy individuals, HIES patients with
STAT3 mutations and HIES patients with only some manifestations
of disease. T cells isolated from peripheral blood were sorted
by flow cytometry and analyzed for intracellular cytokines after
stimulation with staphylococcal enterotoxin B. IL-17- producing
T cells were found in the blood of HIES patients without STAT3
mutations but not in those with the mutations. This suggests a
link between susceptibility to infection and the activity of
Th17 regulatory lymphocytes and between STAT3 activity and Th17
generation. Editor's Comment: The observation of HIES-like
effects in those patients with normal STAT3 means that factors
in addition to Th17 exist. Milner JD et al.,
Nature Letters advanced online publication 12 March 2008.
3. Treatment of patients with hypereosinophilic syndrome (HES)
with mepolizumab (M).
Proliferation of eosinophils (E) from precursor cells requires
IL-5 and targeting this cytokine may be useful in treating HES,
a disease that can result in severe organ damage. Here 85
patients with HES and negative for F1P1L1-PDGFRA fusion gene
were given the anti-IL-5 antibody, M, or placebo in an
international, randomized, DBPC trial with the goal of reducing
the amount of prednisone (P) to 10 mg per day or less required
to control their illness. M treatment was effective in P sparing
in 84% and also reduced E in 95% of the patients. Adverse events
were similar in the M and P groups. Editor's comment: M
significantly reduces P -induced side-effects in HES.
Rothenberg ME et al.
New Engl J Med 2008; 358:1215. Wechsler ME,
4. Chronic exposure to beta-blockers attenuates
inflammation and mucin content in a murine asthma model.
Data from the mouse model of allergic asthma show that
chronic treatment with beta blockers improves airway
hyperresponsiveness (AHR). This report examines the mechanism of
the effects of chronic inhibition of beta adrenoceptor activity
in this model. Administration of beta blockers for 28 days
reduced total cell counts, eosinophils, and IL-13, IL-10, IL-5
and TGF-β1 levels in the bronchoalveolar lavage and attenuated
epithelial mucin content and morphologic changes. Editor's
Comment: Manipulation of the beta adrenoceptor pathway for
asthma treatment needs to be reexamined. Nguyen LP et al.
Am J Resp Cell Molec Biol 2008; 38:256.
5. Allergen induces the migration of platelets (P) to lung
tissue in allergic asthma.
There is substantial evidence that P activation is associated
with increased lung inflammation and bronchoconstriction.
Ovalbumin (OVA)-allergic mice were challenged with OVA and their
lungs examined for P recruitment. Comparisons with mice lacking
FcξRIγ showed platelet migration from the blood into the lungs
in response to allergen in wild-type (WT) but not in mice
deficient in IgE receptor. Platelets isolated from human allergy
patients as well as those from WT (but not FcRγ-/-) mice also
migrate in vitro toward the relevant allergen. Editor's
Comment: The role of platelets in lung inflammation needs to be
elucidated along with other inflammatory cells. Pitchford SC
Am J Resp Crit Care Med 2008; 177:604.
Y, et al. Immunity. 2008 Apr;28(4):581-9. ）の主旨と一致している。
6. Cetuximab(C)-induced anaphylaxis (A) and IgE specific
C is a humanized monoclonal antibody against epidermal growth
factor receptor (EGFR) used to treat colorectal and squamous-cell
carcinoma of the head and neck. Its use is accompanied by a
relatively high incidence of A. This study shows that there were
25 hypersensitivity reactions in 76 patients undergoing C
treatment for cancer. IgE to the sugar,
galactose-α-1,3-galactose, present on the antibody heavy chain,
were found in 17 of these 25 subjects versus one of 51 subjects
without A. A occurred in some subjects the first time they
received C indicating that the offending IgE was already
present. While all humans have IgG against
galactose-α-1,3-galactose, only some individuals develop the
corresponding IgE. Editor's Comment: Patients under
consideration for C will most likely benefit from screening for
IgE against this oligosaccharide. Chung CH et al.
New Engl J Med 2008; 358:1109.
Cetuximabはepidermal growth factor receptor (EGFR)に対するヒト化モノクローナル抗体で、扁平上皮癌患者等に使用されている。アナフィラキシーの報告は多く、76名中、25に過敏症状がみられた。この原因抗原はCetuximabに存在する抗体に存在する糖鎖galactose-α-1,3-galactoseであった。全ての患者はこの抗原に対するIgG抗体を保有していて、一部の患者はIgE抗体を産生した。
7. Factor analysis in the Genetics of Asthma International
Network (GAIN) family study identifies five major quantitative
The pathogenesis of asthma involves a complex interplay of
genetic and environmental influences, and this report attempts
to identify distinct asthma phenotypes by factor analysis. Six
countries and 11 centers form the database for the GAIN study
and from it was drawn a group of asthmatic subjects, age 7-35.
They and their symptomatic siblings were subjected to factor
analysis for asthma phenotype and five distinct factors were
identified: FEV1 and FVC, allergen skin prick test (SPT),
self-reported allergies, rhinitis symptoms and asthma symptoms.
Comparisons among siblings show that these factors are
consistent with shared genetic and environmental influences.
Factor scores correlate with IgE levels, methacholine PC20, age
and asthma severity and may be better for defining asthma
phenotypes than SPT or IgE alone. Editor's Comment: While
this is an important study, the fact that it is cross-sectional
rather than longitudinal is a weak point. Pillai SG et al.
Clin Exp Allergy 2008; 38:421.
６つの国で共同でおこなわれているGenetics of Asthma International Network
プリックテスト (SPT), アレルギーに関する自己報告, 鼻炎症状、喘息症状、以上の５つにより
8. Factors predicting anaphylaxis (A) to peanuts (P) and
tree nuts (TN) in patients referred to a specialist center.
Data from a group of 1094 patients with P and TN allergy
compiled over 12 years were compared in terms of whether P or TN
were involved, severity of associated disease (eczema, asthma
and rhinitis), allergen-specific IgE and SPT results, and in 122
patients, the serum level of angiotensin-converting enzyme (ACE)
and aminopeptidase P (APP). The analysis found a higher rate of
pharyngeal edema in patients with severe rhinitis and low ACE
levels. Severe bronchospasm tended to occur in those with severe
versus mild asthma and severe eczema with altered consciousness.
Editor's comment: The "allergen shock organ" and low ACE
levels help predict the clinical manifestations of A.
Summers CW et al.
J Allergy Clin Immunol 2008; 121:632.
9. A comparison of inflammatory mediators released by
basophils (B) of asthmatic and control subjects in response to
high-affinity IgE receptor aggregation.
B are a small but important set of leukocytes in allergic
reactions and their effects are mediated through activation of
the FcξRIs on their surface. Human B from 16 healthy and 12
asthmatic volunteers were analyzed in this study for cytokine
and chemokine levels before and after binding of IgE to the
receptors and correlated with histamine release and skin prick
test (SPT). Both normal and asthmatic B produced GM-CSF, MIP-5
and eotaxin. Leptin was also produced in most samples and IL-8
in response to IgE cross-linking. No difference in cytokine
release from B was seen in healthy versus asthmatic subjects.
Editor's Comment: The secretion of leptin by B is an interesting
finding that needs confirmation. Gilmartin L et al.
Int Arch Allergy Immunol 2008; 145:182.
10. Primary nasal epithelium exposed to house dust mite (HDM)
extract shows activated expression in allergic individuals.
Epithelial cells (EC) are more than just bystanders in the
establishment of an immune response. Here EC from nasal biopsies
of five allergic and five healthy individuals were cultured with
or without HDM extract and isolated RNA was used for gene
expression profiling by microarray analysis. Results were
verified by quantitative real-time PCR. HDM triggered
up-regulation of two transcription factors (NFkappaB and AP-1)
in healthy epithelium, as well as a number of chemokines, growth
factors and structural proteins. In allergic individuals,
however, these pathways were already activated and HDM did not
change the expression of NFkappaB but did down-regulate AP-1.
Editor's Comment: The finding of specific differences in
allergen-induced gene expression response in allergic
individuals may point the way to new diagnostic and therapeutic
tools. Vroling AB et al.
Am J Resp Cell Molec Biol 2008; 38:293.
11. Phenotypic characterization of T lymphocytes in COPD:
abnormal CD4+CD25+ regulatory T-lymphocyte response to tobacco
Why do some smokers develop COPD and others not? That was the
question posed in this investigation of 23 patients with
moderate COPD, 29 healthy smokers and seven never-smoker
volunteers. T cells were isolated from bronchoalveolar lavage
fluid (BALF) and from peripheral blood and characterized as CD4+
or CD8+, according to the maturation (CD45RA and CD45RO),
activation CD28 markers and to explore potential Treg
abnormalities. Results show that BALF T cells from COPD patients
have higher CD8+CD45RA+ levels and lower CD8+CD45RO+ levels than
smokers with normal lung function. Compared with never-smokers,
smokers with preserved lung function showed a prominent
up-regulation of Tregs absent in COPD. T cells from peripheral
blood did not show any significant differences among the three
groups of patients. Editor's Comment: The lower Treg activity
in the lungs of COPD patients may be involved in pathogenesis of
the disease. Barcelo B et al.
Eur Resp J 2008; 31:555.
Immunity; The Immune Response in Infectious and Inflammatory Disease
Authors: Anthony L DeFranco, Richard M Locksley, Miranda Robertson
Available from: New Science Press Ltd, 2007
List Price: 49.95 USD
Clinical Immunologist, and Professor of Clinical Education, University of Western Sydney, Campbelltown, NSW, Australia
This first edition is part of the "Primers in Biology" series, with an emphasis on immunobiology rather than clinical immunology. The design is unique, with information generally condensed into reasonably brief paragraphs, and accompanied by 367 high quality illustrations that are also available for teaching purposes on line.
The strength of this new textbook lies in the large amount of authoritative information contained in a concise format. Those with some background knowledge will be able to update and refresh, aided by the provision of handy definitions and literature references at the bottom of most pages. This will prove a valuable resource for those involved in the teaching of immunology. For students new to the subject, the concise presentation may prove a barrier to understanding a complex topic.
The role of the immune system in the pathophysiology of infection is well covered. The section covering the interaction of the immune system with the inflammatory response is certainly superior to most of its competitors. As with many of its peer texts, however, the coverage of autoimmune disease and clinical allergy is somewhat cursory, with brief mention only of treatment options. Information on therapeutics is probably best sought elsewhere.
Immunity will appeal to those who appreciate a blend of economy of narrative, and diversity of illustrative techniques. A large amount of up-to-date basic immunologic science is included. This book will prove a useful addition to the existing immunobiology literature.
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