Non‐IgE‐mediated gastrointestinal food allergies in children

Non‐IgE‐mediated gastrointestinal food allergic disorders (non‐IgE‐GI‐FA) including food protein‐induced enterocolitis syndrome (FPIES), food protein‐induced enteropathy (FPE), and food protein‐induced allergic proctocolitis (FPIAP) are relatively uncommon in infants and young children, but are likely under‐diagnosed. Non‐IgE‐GI‐FA have a favorable prognosis, with majority resolving by age 3–5 years. Diagnosis relies on the recognition of symptoms pattern in FPIAP and FPIES and biopsy in FPE. Further studies are needed for a better understanding of the pathomechanism, which will lead eventually to the development of diagnostic tests and treatments. Limited evidence supports the role of food allergens in subsets of constipation, gastroesophageal reflux disease, irritable bowel syndrome, and colic. The immunologic pathomechanism is not fully understood and empiric prolonged avoidance of food allergens should be limited to minimize nutrient deficiency and feeding disorders/food aversions in infants.     

Non‐IgE‐mediated gastrointestinal allergies—Do they have a place in a new model of the Allergic March

The rise in food allergy has been described as the “second wave” of the allergy epidemic, with some developed countries reporting a prevalence of 10% of challenge‐proven food allergies. Recognition of the Allergic March has played a crucial role in identifying causality in allergic conditions, linking atopic dermatitis to food allergy and food allergy to other atopic disorders, thereby highlighting opportunities in prevention and the importance of early intervention. This publication will establish the value of weaving the less well‐understood, non‐IgE‐mediated food allergy into the Allergic March and mapping its progression through childhood and its associated co‐morbidities. The proposed non‐IgE‐mediated Allergic March highlights the concomitant presentation of gastrointestinal symptoms and atopic dermatitis as early presenting symptoms in confirmed non‐IgE‐mediated allergies and the later development of atopic co‐morbidities, including asthma and allergic rhinitis, similar to the IgE‐mediated Allergic March. This publication highlights recent observations of a link between non‐IgE‐mediated food allergy in early childhood and functional gastrointestinal disorders in later life and also the reported occurrence of extra‐intestinal manifestations at later ages. Although significant limitations exist in regard to the proposed evolution of the Allergic March model, the authors hope that this publication will influence the management of non‐IgE‐mediated gastrointestinal allergies and inform future research and interventions.     

IgE‐mediated latex allergy – An exciting and instructive piece of allergy history

Niggemann B. IgE‐mediated latex allergy – An exciting and instructive piece of allergy history.
Pediatr Allergy Immunol 2010: 21: 997–1001.
© 2010 John Wiley & Sons A/S Natural rubber latex represents a potent allergen, which for many years had an important impact on occupational health problems but especially on certain risk groups such as spina bifida. Luckily, these problems decreased when powder‐free, latex‐poor gloves were introduced. Latest data show that in children with spina bifida, who grew up completely latex‐free from birth on, sensitization to NRL as well as clinical relevant allergy significantly decreased. Furthermore, sensitization to aeroallergens also went down and even the prevalence of allergic diseases decreased significantly to rates of the general population. This new data clearly indicates that potent allergens (such as latex) in high‐risk groups (such as spina bifida) can induce sensitization spreading, and corresponding avoidance can reverse this development. In conclusion, it can be stated that ‘new’ allergies can suddenly arise, there are allergen‐specific risk groups, local IgE‐production is also possible in the CNS, allergen avoidance can be very effective in terms of primary prevention, sensitization spreading can be made reversible by effective prevention, and finally, certain allergies can luckily become history within a relatively short period of time. Furthermore, these new findings clearly end the debate about whether patients with spina bifida have a disease‐inherited risk for allergy to NRL and show that the cause is the meningi and the multiple surgical interventions – and therefore sequelae can be reversed by implementing preventive measures.     

437例变态反应性疾病患儿血清特异性IgE抗体检测和分析

目的：了解长沙地区儿童变态反应性疾病的过敏原状况。方法：采用AllergyScreen过敏原定量检测系统检测437例变态反应性疾病患儿血清中总IgE和特异性IgE抗体水平。结果：总IgE阳性率为68.9%,特异性IgE阳性率为69.1%;常见过敏原为户尘螨粉尘螨、牛肉、羊肉、牛奶、猫狗毛皮屑。户尘螨粉尘螨阳性率在变应性鼻炎中最高,达86.0%,特应性皮炎次之,为41.2%,湿疹、荨麻疹相对较低,分别为27.6%,20.0%;猫狗毛皮屑在特应性皮炎、湿疹中相对较高,为23.5%和18.1%,在荨麻疹和变应性鼻炎中较低,为10.0%和8.7%;牛奶、牛肉、羊肉的阳性率在这4种过敏性疾病中均较高,但在4种过敏性疾病之间差别不明显。3岁以上吸入性过敏原阳性率明显高于3岁以下（P＜0.01）。结论：在长沙地区,过敏原对儿童变态反应性疾病有着重要影响,特别是户尘螨粉尘螨、猫狗毛皮屑、牛肉、羊肉、牛奶。［中国当代儿科杂志,2009,11（7）：543-545］     

Elevated cord blood IgE is associated with recurrent wheeze and atopy at 7 yrs in a high risk cohort

There is considerable interest in identifying children at high risk for developing atopic diseases for primary prevention. This study evaluates risk factors for detectable cord blood IgE and assesses CB‐IgE in predicting asthma and other IgE‐mediated allergic diseases in children at high risk because of family history. Cord blood was obtained as part of a randomized controlled trial assessing the efficacy of an intervention program in the primary prevention of IgE‐mediated allergic diseases. CB‐IgE was measured and the degree to which this was associated with perinatal risk factors was assessed. The cohort was then evaluated for atopic disorders at 7 yrs of age to assess the predictive value of CB‐IgE. Fifty‐five (19.3%) of infants had detectable CB‐IgE (≥0.5 kU/l). Maternal atopy and birth in winter months were risk factors associated with detectable CB‐IgE. CB‐IgE was found to be significantly associated with allergic sensitization (OR 2.22; 95% CI 1.11, 4.41) and recurrent wheeze at 7 yrs (OR 2.51, 95% CI 1.09, 5.76) but not with other outcomes. CB‐IgE may be a useful measure for identifying children at high risk of atopic diseases for the purpose of primary prevention.     

Anaphylaxis induced by oral methylprednisolone in a 10‐year‐old boy

Corticosteroids are potent anti‐inflammatory and anti‐allergic agents used in the treatment of various inflammatory diseases, including allergic diseases. Allergic reactions caused by corticosteroids, however, have been reported. Among these, delayed reactions to topical steroids are more common, whereas immediate reactions to systemic steroids are rare. Herein, we report the case of a 10‐year old boy with methylprednisolone‐induced anaphylaxis, in which the patient had a positive oral challenge test result. Physicians should be aware of the possibility of anaphylaxis or other allergic hypersensitivity in response to corticosteroids.     

Fish allergy in childhood

Fish and its derived products play an important role in human nutrition, but they may also be a potent food allergen. Fish can be an ingested, contact, and inhalant allergen. Gad c I, a Parvalbumin, the major allergen in codfish, is considered as fish and amphibian pan‐allergen. Prevalence of fish allergy appears to depend on the amount of fish eaten in the local diet. In Europe, the highest consumption occurs in Scandinavian countries, Spain and Portugal. In Spain, fish is the third most frequent allergen in children under 2 yr of age after egg and cow’s milk. An adverse reaction to fish may be of non‐allergic origin, due to food contamination or newly formed toxic products, but the most frequent type of adverse reactions to fish are immunologic‐mediated reactions (allergic reactions). Such allergic reactions may be both IgE‐mediated and non‐IgE‐mediated. Most cases are IgE‐mediated, due to ingestion or contact with fish or as a result of inhalation of cooking vapors. Some children develop non‐IgE‐mediated type allergies such as food protein induced enterocolitis syndrome. The clinical symptoms related to IgE‐mediated fish allergy are most frequently acute urticaria and angioedema as well as mild oral symptoms, worsening of atopic dermatitis, respiratory symptoms such as rhinitis or asthma, and gastrointestinal symptoms such as nausea and vomiting. Anaphylaxis may also occur. Among all the species studied, those from the Tunidae and Xiphiidae families appear to be the least allergenic.     

Expression of and responses to CD2 and CD3 in 18‐month‐old children with and without atopic dermatitis

We hypothesize that atopy is associated with a reduced T‐cell function early in life and an imbalance in cytokine production. The purpose of this study was to investigate the expression of and responses to CD2 and CD3 in children who did or did not develop atopic dermatitis early in life. The expression of CD2 and CD3 was analyzed by flow cytometry, and proliferation of CD2 and CD3 was studied by ³H‐thymidine incorporation in phytohaemagglutinin (PHA)‐ and anti‐CD3‐stimulated peripheral blood mononuclear cells (PBMC) of 18‐month‐old children, 25 with and 29 without atopic dermatitis. Exogenous interleukin (IL)‐2 was added to compensate for possible functional differences in accessory cells. Anti‐CD3‐induced secretion of IL‐4, IL‐5, IL‐6, IL‐10, IL‐13, and interferon‐γ (IFN‐γ) was analyzed by enzyme‐linked immunosorbent assay (ELISA). Atopy was associated with a low proportion of CD2⁺ lymphocytes. Responsiveness to PHA, which activates lymphocytes partly via the sheep erythrocyte receptor, CD2, was reduced in the allergic children. The anti‐CD3‐induced proliferation declined more rapidly with antibody dilution in the allergic than in the non‐allergic children. Atopic dermatitis was associated with high levels of anti‐CD3‐stimulated IL‐5 secretion. The IL‐4/IL‐10 and IL‐4/IFN‐γ ratios were higher in children with elevated total immunoglobulin E (IgE) levels. Skin prick test‐negative children with eczema produced higher levels of IL‐10 than skin prick test‐positive children. In conclusion, atopic children have a reduced T‐cell function. Atopic dermatitis is associated with increased IL‐5 production, while high total IgE levels are associated with high IL‐4/IFN‐γ and IL‐4/IL‐10 ratios.     

Non‐surgical treatment of adenoidal hypertrophy: The role of treating IgE‐mediated inflammation

Scadding G. Non‐surgical treatment of adenoidal hypertrophy: The role of treating IgE‐mediated inflammation
Pediatr Allergy Immunol 2010: 21: 1095–1106.
© 2010 John Wiley & Sons A/S Adenoidal hypertrophy (AH) and adenotonsillar hypertrophy are common disorders in the pediatric population and can cause symptoms such as mouth breathing, nasal congestion, hyponasal speech, snoring, and obstructive sleep apnea (OSA), as well as chronic sinusitis and recurrent otitis media. More serious long‐term sequelae, typically secondary to OSA, include neurocognitive abnormalities (e.g. behavioral and learning difficulties, poor attention span, hyperactivity, below‐average intelligence quotient); cardiovascular morbidity (e.g. decreased right ventricular ejection fraction, left ventricular hypertrophy, elevated diastolic blood pressure); and growth failure. Adenoidectomy (with tonsillectomy in cases of adenotonsillar hypertrophy) is the typical management strategy for patients with AH. Potential complications have prompted the investigation of non‐surgical alternatives. Evidence of a pathophysiologic link between AH and allergy suggests a possible role for intranasal corticosteroids (INS) in the management of patients with AH. This article reviews the epidemiology and pathophysiology of AH with a particular focus on evidence of its association with allergy and allergic rhinitis. Current treatment options are briefly considered with discussion on the rationale and evidence for the use of INS.     

Glucocorticoids enhance interleukin‐4 production to neo‐antigen (hyaluronidase) in children immunocompromised with cytostatic drugs

Immunoglobulin E (IgE)‐mediated immediate‐type allergic reactions to hyaluronidase have been observed in children with central nervous system (CNS) tumors. Glucocorticoids, used as therapy for brain edema, are discussed controversially as T helper 2 (Th2) stimulatory factors. In this study we investigated the role of glucocorticoids on a Th2 cytokine‐promoting effect in children with CNS tumors. Peripheral blood mononuclear cells (PBMCs) from: 29 children suffering from malignant brain tumors, of whom 23 received short‐term glucocorticoid treatment (for 3–4 days) during the course of chemotherapy; 18 children with nephrotic syndrome or renal transplantation receiving long‐term glucocorticoid treatment; and 13 healthy children, were incubated with phytohemagglutinin (PHA) and/or anti‐CD28 monoclonal antibody (mAb) and, in a second approach, with hyaluronidase. The concentrations of Th cell‐mediated cytokines – interleukin (IL)‐4, IL‐10, and interferon‐γ (IFN‐γ) – were measured in supernatants. The IL‐4 production of PBMCs incubated with PHA/anti‐CD28 mAb from children with repeated co‐administration of glucocorticoids, hyaluronidase, and cytostatic drugs (median: 249.9 pg/ml; range: 234.4–261.7) was significantly higher (p < 0.0001) than IL‐4 production of PBMC from children of all the other groups (median: 86.18; range: 16.0–212.5). There was no significant difference in the levels of IL‐10 and IFN‐γ within the groups. PBMCs stimulated only with hyaluronidase failed to produce detectable levels of cytokines. The results of this study indicate that repeated co‐administration of glucocorticoids and hyaluronidase (a neo‐antigen) enhance IL‐4 production in vitro and thus may induce the production of specific IgE antibodies in children immunocompromised with cytostatic drugs. Hyaluronidase itself does not stimulate in vitro IL‐4 synthesis in PBMCs of children receiving cytostatic drugs.     

IgE response and its regulation in allergic diseases

The distinguishing feature of the allergic person is his or her elevation of serum IgE. This propensity to develop a sustained IgE response is determined genetically. The biologic effects of IgE are mediated via Fc receptors (Fc epsilon R) present on mast cells and basophils (Fc epsilon R type 1) and subpopulations of monocytes, macrophages, eosinophils, and platelets (Fc epsilon R type 2). Interaction of allergen with IgE on these cells results in receptor "bridging" and the release of histamine and other inflammatory mediators. Fc epsilon R type 2 on lymphocytes and monocytes are upregulated in atopic disease and may play a role in the allergic inflammatory reaction. The activation of B cells to synthesize IgE requires several stages (see Fig. 2). T cells play an important role in the regulation of IgE synthesis. In vitro activation of resting B cells to synthesize IgE requires direct cellular interaction with T cells or the presence of IL4 for activation. The latter effect is inhibited by alpha-interferon. Preactivated B cells are influenced in an isotype-specific manner by T-cell-derived IgE binding factors (IgE-BF), which may act as IgE-potentiating or IgE-suppressive factors, depending on their degree of glycosylation. The regulation of IgE synthesis is an important area of investigation. It provides us with an understanding of the basis of the human allergic response and ultimately may provide the basis for novel strategies in the treatment of allergic diseases.     

儿童变态反应性疾病过敏原3 504例调查分析

目的：了解儿童变态反应性疾病的过敏原状况,以便于有针对性的预防和治疗。方法：对3 504例各种变态反应性疾病患儿,采用UniCAP100系统检测血清fx5E（食物筛查试验）或Phadiatop（环境吸入性筛查试验）,及血清特异性IgE。结果：过敏性鼻炎、过敏性结膜炎、哮喘及丘疹性荨麻疹患儿的血清环境吸入性变应原阳性率明显高于食物性变应原,而过敏性紫癜及消化道疾病患儿的食物性变应原阳性率明显高于环境吸入性变应原。环境吸入性特异性IgE水平较高,屋尘、户尘螨、粉尘螨大部分达到6级,食物性特异性IgE水平较低,均在3级以下。结论：不同的儿童变态反应疾病的食物和环境吸入过敏原有显著差异,环境吸入性特异性IgE水平较食物性特异性IgE高。［中国当代儿科杂志,2010,12（9）：720-722］     

Human milk polyunsaturated long‐chain fatty acids and secretory immunoglobulin A antibodies and early childhood allergy

The possible protective effect of breast milk against atopic manifestations in infancy, i.e. atopic eczema and food allergy, has been controversial for the last decades. Besides the methodological problems, differences in the composition of human milk could explain these controversies. The aim of this study was to investigate the composition of polyunsaturated fatty acids (PUFA) and secretory immunoglobulin A (S‐IgA) levels to food proteins (ovalbumin and β‐lactoglobulin) and an inhalant allergen (cat) in milk from mothers of allergic and non‐allergic children. Blood samples were obtained at birth and at 3 months from 120 children. Skin prick tests were performed at 6, 12 and 18 months, and the development of atopic diseases was assessed in the children. Breast milk samples were collected from their mothers at birth and monthly during the lactation period. Milk PUFA composition was measured by gas chromatography, and enzyme‐linked immunosorbent assay (ELISA) was used to measure total S‐IgA, anti‐cat S‐IgA, anti‐ovalbumin S‐IgA, and anti‐β‐lactoglobulin S‐IgA. Allergic disease developed in 44/120 children (22/63 children of allergic mothers and 22/57 children of non‐allergic mothers). Lower levels of eicosapentaenoic acid, C20:5 n‐3 (EPA), docosapentaenoic acid C22:5n‐3 (DPA), and docosatetraenoic acid C22:4 n‐6 (DHA) (p < 0.05 for all) were found in mature milk from mothers of allergic as compared to milk from mothers of non‐allergic children. The total n‐6 : total n‐3 and the arachidonic acid, C20:4 n‐6 (AA) : EPA ratios were significantly lower in transitional and mature milk from mothers of allergic children, as compared to milk from mothers of non‐allergic children. The PUFA levels in serum of allergic and non‐allergic children were largely similar, except for higher levels of C22:4 n‐6 and C22:5 n‐6 (p < 0.05 for both) and a higher AA : EPA ratio in serum phospholipids in the former group (p < 0.05). Changes in the levels of milk PUFA were reflected in changes in PUFA serum phospholipids, particularly for the n‐6 PUFA. The AA : EPA ratio in maternal milk was related, however, to the AA : EPA only in serum from non‐allergic children, while this was not the case in allergic children. The levels of total S‐IgA, anti‐cat S‐IgA, anti‐ovalbumin S‐IgA, and anti‐β‐lactoglobulin S‐IgA in milk from mothers of allergic, as compared to non‐allergic, children were similar through the first 3 months of lactation. Low levels of n‐3 PUFA in human milk, and particularly a high AA : EPA ratio in maternal milk and serum phospholipids in the infants, were related to the development of symptoms of allergic disease at 18 months of age. The milk PUFA composition influenced the composition of PUFA in serum phospholipids of the children. We also showed that the lower levels of colostral anti‐ovalbumin S‐IgA and lower total S‐IgA in mature milk from atopic mothers did not influence the development of allergic disease in the children up to 18 months of age. The findings indicate that low α‐linolenic acid, C18:3 n‐3 (LNA) and n‐3 long‐chain polyunsaturated fatty acids (LCP) 20–22 carbon chains, but not the levels of S‐IgA antibodies to allergens, are related to the development of atopy in children.     

Identification of the etiologies of chronic urticaria in children: A prospective study of 94 patients

Jirapongsananuruk O, Pongpreuksa S, Sangacharoenkit P, Visitsunthorn N, Vichyanond P. Identification of the etiologies of chronic urticaria in children: A prospective study of 94 patients.
Pediatr Allergy Immunol 2010: 21: 508–514.
© 2009 John Wiley & Sons A/S The etiologies of chronic urticaria (CU) in childhood remains incompletely understood because of limited data in children. The objective of this study was to examine some of the possible etiologies of CU in children by focusing on the functional autoantibody to FcεRIα and IgE, thyroid autoimmunity, urticarial vasculitis, parasitic infestation and food allergy. Children 4–15 yr of age with CU were investigated for complete blood count, erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), CH₅₀, free‐T4 (FT₄), thyroid stimulating hormone (TSH), anti‐thyroglobulin and anti‐microsomal antibody, autologous serum skin test (ASST), skin prick tests (SPT) for foods, food challenges, and stool examination for parasites. Ninety‐four children who met the criteria for CU were recruited. Patients with physical urticaria were excluded. Eosinophilia and elevated ESR were found in 23% and 13%, respectively. High ANA titers were found in 2%. None of these patients had clinical features of urticarial vasculitis, abnormal CH₅₀ level, abnormal TSH and FT₄. Anti‐thyroglobulin and anti‐microsomal antibodies were not detected. Positive ASST was found in 38%. There were no differences in medication requirement and CU remission between patients with positive and negative ASST. Parasites were found in 5% without clinical correlation. SPT to foods was positive in 35%. Positive food challenges were found in six/nine patients with positive history of food allergy and two/seven patients with negative history. Food avoidance was beneficial to the subgroup of patients with positive history of food allergy only.     

Allergic disease in infants up to 2 years of age in relation to plasma omega‐3 fatty acids and maternal fish oil supplementation in pregnancy and lactation

To cite this article: Furuhjelm C, Warstedt K, Fagerås M, Fälth‐Magnusson K, Larsson J, Fredriksson M, Duchén K. Allergic disease in infants up to 2 years of age in relation to plasma omega‐3 fatty acids and maternal fish oil supplementation in pregnancy and lactation. Pediatr Allergy Immunol 2011; 22 : 505–514. We have previously reported a protective effect of maternal omega‐3 long‐chain polyunsaturated fatty acids (ω‐3 LCPUFA) supplementation in pregnancy and lactation on IgE‐associated eczema and food allergy in the infant during the first year of life. Here we investigate whether the effects of the LCPUFA supplementation on IgE‐associated diseases last up to 2 yr of age and assess the relationship between plasma proportions of ω‐3 PUFAs and the frequency and severity of infant allergic disease. 145 pregnant women, at risk of having an allergic infant, were randomized to daily supplementation with 1.6 g eicosapentaenoic acid (EPA) and 1.1 g docosahexaenoic acid (DHA) or placebo starting in the 25th gestational week and continuing through 3.5 months of breastfeeding. Clinical examinations, skin prick tests and analysis of maternal and infant plasma phospholipid fatty acids and infant specific IgE were performed. No difference in the prevalence of allergic symptoms was found between the intervention groups. The cumulative incidence of IgE‐associated disease was lower in the ω‐3‐supplemented group (6/54, 13%) compared with the placebo group (19/62, 30%, p = 0.01). Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease (p = 0.01–0.05) in a dose‐dependent manner. Higher maternal and infant proportions of DHA and EPA were found if the infants presented none, when compared with multiple allergic symptoms, (p < 0.05) regardless of sensitization. In summary, the ω‐3 supplementation offered no obvious preventive effect on the prevalence of clinical symptoms of allergic disease, but the decrease in cumulative incidence of IgE‐associated disease seen during the first year still remained until 2 yr of age. Furthermore, high proportions of DHA and EPA in maternal and infant plasma phospholipids were associated with less IgE‐associated disease and a reduced severity of the allergic phenotype.     

Anti-IgE-Therapie bei Kindern und Jugendlichen

Immunoglobulin E (IgE) plays a key role in mediating allergic reactions to food and environmental allergens, which are relevant for the expression of allergic symptoms of the airways (rhinoconjunctivitis, bronchial asthma), the skin (urticaria, atopic dermatitis), as well as the gastrointestinal tract (food allergens). The recombinant humanized antibody omalizumab, which became available in Germany in 2005 for the treatment of severe allergic asthma for children aged 12 years and above, has proved its therapeutic efficacy for special cases,as well as its safety in all age groups. In addition to bronchial asthma, anti-IgE offers interesting perspectives for the treatment of complex allergic diseases which have a strong impact on quality of life and have so far been difficult to control.     

Allergen immunotherapy for IgE‐mediated food allergy: There is a measure in everything to a proper proportion of therapy

IgE‐mediated food allergy (FA) is a potentially life‐threatening condition with a negative impact on quality of life and an increasing prevalence in westernized countries in the recent two decades. A strict avoidance of the triggering food(s) represents the current standard approach. However, an elimination diet may be difficult and frustrating, in particular for common foods, (eg, milk, egg, and peanut). Food allergy immunotherapy (FA‐AIT) may provide an active treatment that enables to increase the amount of food that the patient can intake without reaction during treatment (ie, desensitization), and reduces the risk of potential life‐threatening allergic reaction in the event of accidental ingestion. However, several gaps need still to be filled. A memorable Latin orator stated: “Est modus in rebus” (Horace, Sermones I, 1, 106‐07). This sentence remembers that there is a measure in everything to a proper proportion of therapy. The common sense of measure should find application in each stage of treatment. A personalized approaching should consider the specific willing and features of each patient. Efforts are devoted to improve the efficacy, the safety but also the quality of life of patients suffering from FA. In the near future, it will be important to clarify immunologic pathways of FA‐AIT, and to identify reliable biomarkers in order to recognize the most suitable candidates to FA‐AIT and algorithms for treatments tailored on well‐characterized subpopulations of patients.     

Marked thrombocytopenia in a neonate is associated with anti‐HPA‐5b,anti‐HLA‐A31, and anti‐HLA‐B55 antibodies

Maternal antibodies against human platelet antigen (HPA) and/or human leukocyte antigen (HLA) cause fetal and neonatal alloimmune thrombocytopenia (FNAIT) in 0.09‐0.15% of live births. Severe cases account for 5‐31% and the frequency of multiple kinds of alloantibodies is 6.9‐9% of FNAIT. We present a case of severe FNAIT associated with anti‐HPA‐5b, anti‐HLA‐A31, and anti‐HLA‐B55 antibodies, successfully treated with immunoglobulin and platelet transfusion. The anti‐HLA‐B55 antibody was detected in the newborn's serum, but disappeared on the 20th day, which was followed by an increase of the platelet count. These findings suggested the potential involvement of an anti‐HLA antibody in the pathogenesis of FNAIT.     

Primary mediastinal large B‐cell lymphoma: Outcome of a series of pediatric patients treated with high‐dose methotrexate and cytarabine plus anti‐CD20

Between 2007 and 2013, 13 children diagnosed with primary mediastinal large B‐cell lymphoma (PMLBL) were treated according to a modified version of AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) LNH‐97 protocol based on high‐dose methotrexate, anthracyclines, and addition of anti‐CD20. Ten patients achieved a continuous complete remission with front‐line therapy. The overall 5‐year survival was 91.7%, and event‐free survival was 83.9%, with only one patient dying of progressive disease. Despite the few cases, these results demonstrate that this therapy, which includes anti‐CD20, given in a multicenter setting, is feasible with acceptable toxicity in children with PMLBL.     

Interleukin‐33 in the developing lung—Roles in asthma and infection

It has become increasingly clear that interleukin‐33 (IL‐33) plays a crucial role in initiation of type 2 immunity. The last decade of intense research has uncovered multiple mechanisms through which IL‐33 targets key effector cells of the allergic immune response. Recently, IL‐33 has been implicated in shaping the immune system of the lungs early in life, at a time which is crucial in the subsequent development of allergic asthma. In this review, we will address the current literature describing the role of IL‐33 in the healthy and diseased lung. In particular, we will focus on the evidence for IL‐33 in the development of immune responses in the lung, including the role of IL‐33–responsive immune cells that may explain susceptibility to allergic sensitization at a young age and the association between genetic variants of IL‐33 and asthma in humans. Finally, we will indicate areas for potential therapeutic modulation of the IL‐33 pathway.