A.M. Plaza-Martín

Safety and predictors of adverse events during oral immunotherapy for milk allergy: severity of reaction at oral challenge, specific IgE and prick test

Strict avoidance is the only accepted management for cows milk (CM) allergy. CM oral immunotherapy (CM‐OIT) is under investigation.

Polysensitization to aeroallergens and food in eosinophilic esophagitis in a pediatric population

There are few studies on eosinophilic esophagitis (EE) in the pediatric population in Europe. We present our data and emphasize the following findings: a) all patients had symptoms of allergic respiratory disease prior to receiving a diagnosis of EE with polysensitization (aeroallergens, food allergens); and b) in contrast with the results of earlier studies, food sensitization in our series most often corresponded to legumes.

Eosinophilic oesophagitis: clinical manifestations and treatment options. The role of the allergologist.

Eosinophilic oesophagitis (EO) is an infrequent disorder that is currently underdiagnosed. It has been described in both adults and in children, and is more prevalent among males. The etiology of EO is not clear, though atopy has been suggested as playing an important role in the development of the disease. The clinical presentation of EO is varied, and a differential diagnosis with other digestive tract disorders is required particularly gastro-oesophageal re-flux. Dysphagia and food bolus impactation within the oesophagus are the most characteristic symptoms. Diagnostic confirmation is obtained from multiple oesophageal biopsy, with the detection in some sample or samples of over 15 eosinophils per high-magnification microscopic field. An allergological study is needed to evaluate the existence of allergens (perennial or seasonal environmental allergens and food allergens) responsible for the eosinophilic infiltration found at oesophageal level. There is no specific treatment for EO, and topical corticosteroids (swallowed) are currently the pharmacological treatment of choice. Dietary therapy in children with food allergy as the causal factor may prove effective, though the existence of polysensitisation complicates the correct implementation of such treatment. Oesophageal dilatation is reserved for cases with severe dysphagia, and is not without complications. Treatment with anti-IL-5, antileukotrienes, azathioprine, 6-mercaptopurine, anti-IgE, etc., could constitute alternatives to topical corticosteroids, although information is still lacking on their long-term safety and efficacy in the paediatric population.

Immunological Changes in Blood of Newborns Exposed to Anti-TNF-α during Pregnancy

Background Although anti-TNF-α monoclonal antibodies are considered safe during pregnancy, there are no studies on the development of the exposed-infant immune system. The objective was to study for the first time the impact of throughout pregnancy exposure to anti-TNF-α has an impact in the development of the infant’s immune system, especially B cells and the IL-12/IFN-γ pathway. Methods Prospective study of infants born to mothers with inflammatory bowel disease treated throughout pregnancy with anti-TNF-α (adalimumab/infliximab). Infants were monitored both clinically and immunologically at birth and at 3, 6, 12, and 18 months. Results We included seven patients and eight healthy controls. Exposed infants had detectable levels of anti-TNF-α until 6 months of age; they presented a more immature B- and helper T-phenotype that normalized within 12 months, with normal immunoglobulin production and vaccine responses. A decreased Treg cell frequency at birth that inversely correlated with mother’s peripartum anti-TNF-α levels was observed. Also, a decreased response after mycobacterial challenge was noted. Clinically, no serious infections occurred during follow-up. Four of seven had atopia. Conclusion This study reveals changes in the immune system of infants exposed during pregnancy to anti-TNF-α. We hypothesize that a Treg decrease might facilitate hypersensitivity and that defects in IL-12/IFN-γ pathway might place the infant at risk of intracellular infections. Pediatricians should be aware of these changes. Although new studies are needed to confirm these results, our findings are especially relevant in view of a likely increase in the use of these drugs during pregnancy in the coming years.

Asymptomatic LTP sensitisation is common in plant-food allergic children from the Northeast of Spain.

BACKGROUND The sensitisation profile at molecular level in plant-food allergy is complex. Several allergens may be involved, with different potential for severe reactions. lipid transfer proteins (LTP) are considered the most relevant plant-food allergens in adults in Mediterranean countries, but less is known in children. AIM To describe the clinical pattern and sensitisation profile of children with plant-food allergy and LTP sensitisation from Northeast Spain. METHODS Children with history of immediate reaction to plant-food(s), positive skin-prick-test to the culprit plant-food(s) and specific-IgE to plant-food LTPs were analysed. RESULTS 130 children were included. 69.2% (90/130) had reacted to ≥2 taxonomically unrelated plant-foods. Peach, walnut, hazelnut and peanut were most frequently involved. Reactions severity ranged from anaphylaxis (45.4%, 59/130) to oral symptoms only. Sensitisation to a particular plant-food LTP not always caused clinical symptoms with that plant-food; 69% (40/58) and 63% (17/27) of peach- and walnut-tolerant subjects had positive rPru p 3 and nJug r 3 specific IgE, respectively. 65.4% (85/130) of children were also sensitised to storage proteins, which was associated to anaphylaxis and nut allergy. However, 60% of patients without nuts/seeds allergy were sensitised to storage proteins. Specific-IgE levels to LTPs and/or storage proteins were not useful to predict allergy (vs. tolerance) to peach, walnut, peanut or hazelnut. CONCLUSIONS Sensitisation to LTP and/or storage proteins without clear clinical significance is relatively common. Prospective longitudinal studies are required to evaluate the relevance of these silent sensitisations over time. Caution is required when interpreting the results of molecular-based diagnostic tools in clinical practice.

Can total IgE/specific IgE ratio predict tolerance in cow's milk allergic children?

due to development of wheezing. In summary, we report the first case of a pediatric patient with IgE-mediated allergy to glatiramer acetate, presenting with a severe systemic reaction, in whom a novel and successful desensitization protocol was applied that allowed her to resume the use of this medication. Furthermore, we have established a skin test protocol which can potentially be helpful in evaluating patients with suspected IgE-mediated reactions to glatiramer acetate. Our experience supports the notion that allergy evaluation and desensitization can be helpful in pediatric patients with a history of hypersensitivity reactions to glatiramer acetate and may allow continuation of this extremely powerful therapeutic agent available for the treatment of MS.

Lymphoma as presentation of common variable immunodeficiency

taxenes, platinum salts, L-asparaginase and monoclonal antibodies involving anaphylactic or anaphylactoid reactions. To date no desensitisation protocols have been published on third generation aromatase inhibitors like AN. In these case reports both patients referred late reactions to AN with mainly cutaneous symptoms. To clarify the underlying mechanism of these reactions, patch tests with 10 % AN in white petrolatum were performed with negative results. This could have several explanations: the fi nal responsible agent for the reaction could be a metabolite of AN; poor penetration of the drug into the epidermis; low drug concentration, use of inappropriate vehicle and immunosuppression state of patients. Although no immune mechanism could be proven in our patients, a desensitisation procedure was tried with success. This result reinforces the fact that desensitisation to drugs that induce delayed cutaneous hypersensitivity reactions is possible and safe, as we have observed many times in patients with HIV infection and delayed cutaneous reactions to cotrimoxazol.

Characterization of the Highly Prevalent Regulatory CD24hiCD38hi B-Cell Population in Human Cord Blood

The newborn’s immune system must transition from a sterile haploidentical uterus to the world full of antigens. Regulatory B-cells (Breg; broadly defined as CD19+CD24hiCD38hi) are tolerance promoters in the adult immune system. They can inhibit IFN-γ and IL-17 production by T-cells and are essential in different conditions, including pregnancy. Breg have still not been well characterized in umbilical cord blood, where we hypothesize that they are pivotal in the achievement of tolerance. We studied CD19+CD24hiCD38hi Breg in healthy umbilical cord blood (hUCB) compared to healthy peripheral adult blood (hAPB). Total numbers of Breg were increased in hUCB compared to hAPB (34.39 vs. 9.49%; p = 0.0002), especially in the marginal zone-like B-cell subset, in which the most marked difference could be observed between hUCB and hAPB (60.80 vs. 4.94%; p = 0.1). CD24hiCD38hi subset in hUCB produced IL-10 and inhibited T-cell IFN-γ [1.63 vs. 0.95 stimulation ratio (SR); p = 0.004] and IL-4 (1.63 vs. 1.44 SR; p = 0.39) production. Phenotypically, hUCB Breg cells presented IgMhiIgDhiCD5+CD10+CD27− markers, similar to those described in hAPB Breg cells, but they showed increased IgM concentration and decreased expression of CD22 and CD73 markers. Our work characterized the frequency, phenotype, and function of Breg in hUCB, which may contribute to understanding of immune tolerance during pregnancy, paving the way to a new approach to immune-related diseases in the fetus and the newborn.

Evans Syndrome as First Manifestation of Primary Immunodeficiency in Clinical Practice

Background: Evans syndrome (ES) is a rare immune disorder in children, manifested by simultaneous or sequential autoimmune cytopenias (ACs) of unknown cause and having a chronic course with periods of exacerbation and remission. Some primary immunodeficiencies (PIDs) may present with autoimmune manifestations without infections, masking suspicion of them. The PIDs that can typically manifest as ES are autoimmune lymphoproliferative syndrome and common variable immunodeficiency (CVID). Materials and Methods: Review of clinical charts and laboratory results of pediatric patients followed-up in the outpatient clinic of PID with a diagnosis of ES and humoral immunodeficiency. Results: Three pediatric patients, a boy and 2 girls, presented with corticosteroid-dependent ES. In the diagnostic approach, autoimmune lymphoproliferative syndrome was ruled out, and during follow-up, patients showed laboratory signs of humoral immune deficiency and were diagnosed with CVID. After initiating the recommended treatment for CVID with AC, patients improved without new exacerbations. Conclusions: These cases highlight the importance of detection of possible PID in the context of ES and the establishment of CVID treatment to control AC.

Sirolimus as an alternative treatment in patients with granulomatous-lymphocytic lung disease and humoral immunodeficiency with impaired regulatory T cells

One of the most frequent non‐infectious complications of humoral immunodeficiencies with a CVID‐like pattern is a particular form of inflammatory lung disease which is called granulomatous‐lymphocytic interstitial lung disease (GLILD). Its development worsens patient prognosis, with a significant decrease in survival. Currently, there are no unified guidelines regarding its management, and different combinations of immunosuppressants have been used with variable success.