Download 02-04-12 ALLERGY: • META-ANALYSIS OF CLINICAL TRIALS ON

02-04-12
ALLERGY:
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META-ANALYSIS OF CLINICAL TRIALS ON TRADITIONAL CHINESE HERBAL MEDICINE
FOR TREATMENT OF PERSISTENT ALLERGIC RHINITIS:
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Between 10% and 20% of the population suffer from AR.
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Chinese herbal medicine interventions appear to have beneficial effects in
patients with PAR. However, the published efficacy studies are too small to
draw firm conclusion.
BASOPHILS AND ANTIGEN PRESENTATION: OF MICE AND NOT MEN?
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To be a functional APC, a specific cell should fulfill several capacities: antigen
binding and uptake, antigen processing, loading the antigen onto MHC-II
molecules and finally expressing the loaded MHC-II molecule on the plasma
membrane together with costimulatory molecules. This implicates that the
expression of MHC-II on the plasma membrane of a cell per se does not
designate antigen-presenting properties. This is, for instance, an important
point of debate on the IFN-y-induced MHC-II expression on mast cells or
keratinocytes.
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Human basophils lack protease-activated receptor expression (PAR), and PAR
ligands failed to induce activation of these cells.
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Human basophils cannot be activated through IgG receptors (their functions
are inhibited by IgG-mediated triggering via FcyRIIb receptors).
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It is of great interest to further examine the properties of basophils to present
antigen in different diseases in the context of their proven potent IL-4releasing role. However, one should take into account that even in the case
that basophils are found to present antigen to T cells, it is highly likely that
their role will be a minor one when compared with professional antigenpresenting DCs.
ANNALS OF ALLERGY AND CLINICAL IMMUNOLOGY:
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ANAPHYLAXIS CAUSED BY TETRAZEPAM WITHOUT CROSS-REACTIVITY WITH OTHER
BENZODIAZEPINES:
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Adverse reactions to benzodiazepines are mostly related to overdosing.
Allergic reactions are rare, with only a few cases reported in the literature.
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Tetrazepam challenge oral test: 5, 5, and 15 mg; 30 minutes between doses.
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Diazepam challenge oral test: 1, 2, and 2 mg; 30 minutes between doses.
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Tetrazepam has been described as an inductor of delayed type IV reactions,
such as maculopapular exanthema, Stevens-Johnson syndrome, toxic
epidermal necrolysis, hypersensitivity syndrome, and contact dermatitis.
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We present a case of anaphylaxis to tetrazepam supported by serologic data.
No evidence of cross-reactivity was found with other benzodiazepines,
suggesting a selective IgE-mediated mechanism.
RELATIONSHIP OF 25-HYDROXYVITAMIN D AND ASTHMA CONTROL IN CHILDREN:
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It is accepted that serum 25-hydroxyvitamin D (25[OH]D) levels less than 10 to
12 ng/mL represent deficiency, levels less than 20 ng/mL represent
insufficiency, and levels greater than 30 ng/mL represent sufficiency.
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To assess the therapeutic effect in asthma, a significantly higher dose of
vitamin D supplementation will be necessary beyond the recommendation of
the Institute of Medicine (600 IU) or the American Academy of Pediatrics (400
IU). We observed in our study population that 1,000 IU was inadequate to
increase 25(OH)D levels more than 30 ng/mL in 50% of our study participants
after 1 year of supplementation.
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Vitamin D deficiency has been linked to being overweight and having darker
skin color.
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Future therapeutic trials should be powered sufficiently, and patients
supplemented to vitamin D levels >30 ng/mL during the entire study to reveal
the potential for vitamin D supplementation to improve asthma control.
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In this study, no significant differences were found in ACT scores or spirometry
values between vitamin D–treated and placebo-treated individuals. This may
have been a result of failure to achieve normal 25(OH)D levels in most vitamin
D–treated patients.
ANNALS OF ALLERGY AND CLINICAL IMMUNOLOGY:
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ADMINISTRATION OF INFLUENZA VACCINE TO PEDIATRIC PATIENTS WITH EGGINDUCED ANAPHYLAXIS:
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We report on the relative safety of influenza vaccination in subjects with a
history of egg-induced anaphylaxis. In 119 vaccinations there were 3 cases of
skin-limited reactions and no systemic reactions.
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Higher vaccine ovalbumin content does not increase the risk of a reaction.
CD27: A NEW PLAYER IN THE FIELD OF COMMON VARIABLE IMMUNODEFICIENCY
AND EBV-ASSOCIATED LYMPHOPROLIFERATIVE DISORDER?
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CD27 is routinely used as a marker of memory B cells. A human defect of CD27
might have a substantial effect on cellular and humoral immunity.
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Autosomal recessive CD27 deficiency should be considered in patients with
CVID who lack CD27+ B cells and/or patients with severe courses of EBV
infection, who might be treatable with IVIG and rituximab.
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It remains to be elucidated how the lack of (functional) CD27 contributes to
the pathogenesis of CVID and EBV-associated LPD.
DIAGNOSING NONIMMEDIATE REACTIONS TO CEPHALOSPORINS:
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Cephalosporins can cause nonimmediate reactions (occurring >1 hour and
within 7 days after last drug administration). Main reactions: maculopapular or
morbilliform rashes and delayed-appearing urticaria/angioedema.
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Aminocephalosporins: cephalexin, cefaclor, and cefatrizine.
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Readings of late reactions to IDR were done after 48 and 72 hours; any
infiltrated erythema with a diameter >5 mm was considered positive reaction.
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Most delayed skin manifestations in temporal correlation with cephalosporin
treatments did not were confirmed on IDR or DPT.
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IDR is useful in identifying the cephalosporins responsible for nonimmediate
reactions. Patch testing is not indicated in subjects with mild nonimmediate
reactions to cephalosporins, such as maculopapular and urticarial rashes.
ICON: FOOD ALLERGY:
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Celiac disease (and dermatitis herpetiformis associated with celiac disease) is a
cell-mediated response against an enzyme, tissue transglutaminase, that can
be triggered by an immune response to a food protein, gluten.
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Food allergens are usually proteins but sometimes haptens.
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Food allergens can cause reactions if they are inhaled; this should be
differentiated from inhaling the fragrance of a food.
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Clinical cross-reactivity among legumes is generally uncommon (eg, most
persons with peanut allergy tolerate beans and peas), whereas clinical crossreactivity among different types of crustacean shellfish is common.
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Protein-containing food additives and coloring agents, such as annatto,
carmine, and gelatin, can induce allergic reactions. Chemical additives, such as
artificial flavors (eg, tartrazine) and preservatives (eg, glutamates and sulfites),
might cause adverse reactions, but an immune mechanism has not been
identified, and such reactions are classified as intolerances.
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Food allergy in adults can be a persistent allergy from childhood or de novo
sensitization. Food allergy affects between 1% and 10% of the population.
More than half of presumed food allergies are not allergies.
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Medical history should ask the possible causal food, form of ingestion (raw,
cooked, or baked), quantity ingested, time course of reactions, nature of
reactions, and other factors (as exercise or ingestion of aspirin or alcohol).
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NONIMMEDIATE DRUG ALLERGY: DIAGNOSTIC BENEFIT OF SKIN TESTING AND
PRACTICAL APPROACH:
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TH9 CELLS: IN FRONT AND BEYOND TH2:
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There is currently no established gold standard for the diagnosis of a delayedtype allergy. Romano et al used weekly challenges with first one hundredth
and then one tenth and finally one single therapeutic daily dose. However, it is
well documented that some nonimmediate reactions appear only after a
treatment of several days at full therapeutic dosage. Furthermore, cofactors,
such as concomitant viral infections, are considered important, and these are
normally not present during challenge tests. Thus only a positive test result is
conclusive, and even challenge tests are not an unequivocal gold standard.
The cellular source for IL-9 is not restricted to TH9 cells because other immune
cells, such as mast cells, innate lymphoid cells, NKT cells, and regulatory T cells,
can also produce this cytokine.
THE AIRWAY EPITHELIUM IN CHILDHOOD ASTHMA:
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Irreversible airflow obstruction occurs early in the course of asthma, but in
most patients it does not progress to severe airflow obstruction as asthmatic
patients grow older.
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The reasons for this lack of progression in airflow obstruction are entirely
unexplained and deserve more study.
NATURE REVIEWS IMMUNOLOGY:
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A KILLER COMBINATION:
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A combination of the tumour-targeting antibody trastuzumab (specific for
human epidermal growth factor receptor 2 (HER2)) and a NK cell-activating
antibody specific for CD137 is highly effective in treating breast cancer.
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Trastuzumab leads to the elimination of HER2+ breast cancer cells mainly
through antibody-dependent cell-mediated cytotoxicity by NK cells.
ADOPTIVE IMMUNOTHERAPY FOR CANCER - HARNESSING THE T CELL RESPONSE:
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It seems perplexing that tumours persist despite being enriched for T cells that
are specific for antigens expressed by the tumour. This is perhaps because
tumour-infiltrating lymphocytes (TILs) are restrained by immunosuppressive
molecules, such as T cell immunoglobulin and mucin domain-containing
protein 3 (TIM3), lymphocyte activation gene 3 protein (LAG3), programmed
cell death protein 1 (PD1) and cytotoxic T lymphocyte antigen 4 (CTLA4).
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Immunotherapy based on transfer of naturally occurring or gene-engineered T
cells can mediate tumour regression in patients with metastatic cancer.
COORDINATED REGULATION OF MYELOID CELLS BY TUMOURS:
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3 groups of terminally differentiated myeloid cells: macrophages, dendritic
cells and granulocytes.
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Tumour microenvironment alters myeloid cells and can convert them into
potent immunosuppressive cells.
EDITORIAL SELECTION DEMYSTIFIED:
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The immune system can eliminate immunogenic tumour cells, but such
immune reactivity may lead to the somatic evolution of tumours so that they
are no longer recognized by the immune system. This process is known as
cancer immunoediting.
HOPE IN A STICKY SITUATION:
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During tumorigenesis, hypoxic tumour environment promotes the formation of
abnormal new blood vessels compared with healthy vasculature. Leukocyte
adhesion to endothelial cells lining tumour-associated vasculature is impaired
and, consequently, effector immune cells cannot gain access to the tumour.
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Therapy with a TNF–peptide fusion protein that targets TNF to the tumourassociated vasculature promoted the upregulation of adhesion molecules on
endothelial cells and increased the infiltration of CD8+ T cells into tumours.
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KEEPING VIRUS-DRIVEN LYMPHOMAS IN CHECK:
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EBV is rapidly cleared by the immune system, but it can persist in some cells
for life. Under conditions of immunosuppression, B cells that are latently
infected with EBV can undergo marked proliferation and malignant
transformation. EBV latent membrane protein 1 (LMP1) is essential for the
transformation of human B cells.
SKIN-DEEP MEMORY:
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Skin infection generates non-migratory CD8+ T effector memory cells that
provide global skin immunity against re-infection.
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Alemtuzumab depleted all T cells from the blood, including skin-homing TCM
cells, but did not deplete skin-resident TEM cells. Failure of alemtuzumab to
deplete skin-resident TEM cells was not due to poor skin penetration of the
drug or loss of expression of CD52 by TEM cells, but is thought to result from
the scarcity of neutrophils in the skin to mediate T cell depletion through
antibody-dependent cell-mediated cytotoxicity.
TARGETING NATURAL KILLER CELLS AND NATURAL KILLER T CELLS IN CANCER:
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NK cells and NKT cells are subsets of lymphocytes that share some
phenotypical and functional similarities. Both cell types can rapidly respond to
the presence of tumour cells and participate in antitumour immune responses.
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NKT cells have been classified into four different groups. Only type I (iNKT cells)
and type II NKT cells are CD1d-restricted.
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iNKT cells are unique because they have the ability to respond both as innate
cells, with minimal TCR involvement, and as memory-like cells through the
engagement of their semi-invariant TCR.
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Recent studies indicate that NK cell activation could lead to the generation of
‘memory’ NK cells, a feature that has been ascribed only to B and T cells so far
and that is recognized as the hallmark of the adaptive immune system.
TUMOUR IMMUNOTHERAPY — LEUKOCYTES TAKE UP THE FIGHT:
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Inhibitory signalling pathways that restrict immune cell activation (known as
immune ‘checkpoints’) can be inhibited and such an approach has been shown
to induce regression of melanomas and other types of cancer.
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The immune system can promote the elimination of tumours, but often
immune responses are modulated or suppressed by the tumour
microenvironment.