Ruperto González

T cell activity in successful treatment of chronic urticaria with omalizumab

Omalizumab, a humanized monoclonal anti-IgE antibody has the potential to alter allergen processing. Recently, it has been postulated the assessment of PHA-stimulated adenosine triphosphate (ATP) activity as maker of CD4+ T cells activity in peripheral blood cells. We present the case report of a 35-year-old woman with a history of chronic idiopathic urticaria and angioedema of 8 years of development with poor response to treatment. The patient was partially controlled with cyclosporine at doses of 100 mg/12 h. However, she was still developing hives daily. Finally treatment with omalizumab was started at dose of 300 mg every 2 weeks. The patient experienced a decrease in urticarial lesions 2 days after starting therapy. We also evaluated the effects of omalizumab therapy on the activity of peripheral blood CD4+ T cells from the patient, in order to determine the potential modification of anti-IgE therapy on the process of antigen presentation-recognition. Activity of CD4+ cells by ATP release was clearly increased demonstrating an enlarged CD4 activity. Omalizumab may be useful in the treatment of severe chronic urticaria. ATP activity of peripheral blood CD4+ T cells might be a non-subjective method to assess Omalizumab activity.

Oral mite anaphylaxis by Thyreophagus entomophagus in a child: a case report.

Sensitization to Thyreophagus entomophagus, a storage mite, is uncommon and might produce occupational respiratory disorders in farmers. We present the first case of a child suffering anaphylaxis produced by ingestion of contaminated flour with Thyreophagus entomophagus.

Evaluating the Usefulness of Retesting for Beta-Lactam Allergy in Children.

Many children with adverse reactions to beta-lactams are labeled as allergic without performing an allergy study to confirm it. In this retrospective study of 10 years, we detected only 3.3% positive cases. Although international guidelines recommend a second allergy workup in patients with a negative study, we found from our results a low profitability of retesting.

Accuracy in diagnosis of allergy to β-lactams

There are a large number of patients labelled as allergic to drugs commonly used in clinical practice without having been studied and based only on clinical history. This creates a major health resource problem, having to use alternative treatments, in many cases with higher cost.

IP-10 In Pediatric Celiac Disease and Food Allergy.

physicians and pharmaceutical companies that PML could occur. Th is brings us to the topic of the biological plausibility of the rare event of PML in association with anti-adhesion therapies. We off er as a cautionary example the unexpected immunologic eff ect of serum antibodies to Abciximab. Th is monoclonal antibody therapy was designed to bind to the activated form of platelet glycoprotein IIb / IIIa (aka integrin α IIb β 3 ), and prevent clotting during endovascular procedures without an excess of clinically important bleeding in most patients. However, some patients developed antibodies against the abciximab / platelet complex, which reduced the specifi city of this interaction ( 3 ). When one of these rare patients is treated with abciximab, severe thrombocytopenia occurs, and rapid bleeding from all mucosal surfaces ensues. Although it is unlikely that a similar mechanism might reduce the specifi city of other antiintegrin monoclonal therapies, it is not impossible. Th at this has previously occurred in patients treated with another anti-integrin monoclonal antibody, and that patients with infl ammatory bowel disease (IBD) are prone to autoimmune reactions, makes it unlikely but possible that an unforeseen mechanism in rare patients could reduce the specifi city of an antiα 4 β 7 monoclonal therapy ( Figure 1 ). Suffi cient sample size can change a very rare event to a reasonably likely event. We would like to reiterate that the rule of 3 s provides the upper limit of the 95 % confi dence interval, not the actual estimate of the risk of an event. We agree with the letter writers that PML cases associated with vedolizumab, if they occur at all, will be rare events, and that there are many factors that could aff ect an estimate of the frequency of rare events, including biological plausibility, latency, and other risk factors. We are hopeful that anti-adhesion therapies will prove benefi cial to millions of patients with IBD worldwide, but we should be prepared for the possibility of rare events, including PML. We hope that if PML does occur in the future in association with the newer anti-adhesion therapies, gastroenterologists, the Food and Drug Administration, and the general public will thoughtfully consider the frequency of rare events and embrace the richness of human diversity. To paraphrase Miranda in Shakespeare ’ s Th e Tempest (V,i), O brave new world, that has such biologic processes in it! To dismiss the past (abciximab) and deny the possibility of rare risks in the future would make us ill-prepared for an important potential complication. As vedolizumab leaves the island of clinical trials for the wider world of clinical practice, rare events might occur, but we should not panic or overreact to them. Instead, we should thoughtfully consider the frequency and magnitude of benefi ts in relation to the frequency and magnitude of rare risks .

Safety of Modified Dust Mite Subcutaneous Immunotherapy in Severe Allergic Asthma

U E S D A Y 730 CC10 A38G Polymorphism (rs3741240) Is Associated with Asthma Susceptibility and Bronchial Hyperresponsiveness Mediated by the Eosinophilic Inflammation in Korean Children Kyungmo Hong, Hyun-Kyung Kim, Mi-Jin Kang, MS, Ho-Sung Yu, BS, Byoung-Ju Kim, MD, PhD, Young Ho Jung, MD, Jinho Yu, MD, PhD, Soo-Jong Hong, MD, PhD; Goucher College, Baltimore, USA, Childhood Asthma Atopy Center, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, South Korea, Department of Pediatrics, Hae-undae Paik Hospital, Inje University College of Medicine, Busan, South Korea, Childhood Asthma Atopy Center, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, Research Center for Standardization of Allergic Disease, Seoul, South Korea. RATIONALE: Clara cell secretory protein (CC10) or uteroglobin (secretoglobin, family 1A, member 1 (SCGB1A1)) is produced by nonciliated Clara cells in the respiratory tract. CC10 is believed to function in reducing inflammation, inhibiting phospholipase A2. We investigated the association of the CC10 A38G polymorphism with asthma in Korean children, and to assess the effect of these variants on intermediate phenotypes of asthma. METHODS: Asthmatic children (N5930) and control children (N5578) were evaluated for asthma phenotypes and intermediate phenotype such as IgE, pulmonary function test, and BHR to methacholine. Polymorphism of CC10 (rs3741240) was genotyped by using TaqMan assay. RESULTS: In children with asthma and atopic asthma, the frequencies of the AA genotype were higher than normal controls (aOR 1.60, 1.68; 95% confidence interval (CI) 1.18-2.16, 1.23-2.29, respectively). The AA genotype was associated with higher logECP (p50.031) in children with atopic asthma, and lower PC20 (aOR 1.61; 95% CI 1.05-2.46) values in children with asthma compared to the GG + AG genotypes. CONCLUSIONS: The CC16 A38G polymorphism is associated with the development of asthma and intermediate asthma phenotypes in Korea children. Atopic asthmatic children with AA genotype were associated with higher log ECP level and asthmatic children were also associated with lower PC20 values. Therefore, the AA genotype may be related with an increased risk of asthma and BHR inKorean childrenmediated by airway eosinophilic inflammation. This study was supported by a grant from the Korea Healthcare technology R&D Project, Ministry for Health, Welfare, Republic of Korea (A092076)

Allergen Specific Immunotherapy in Cases of Severe Atopic Dermatitis

S U N D A Y 366 Allergen Specific Immunotherapy in Cases of Severe Atopic Dermatitis Inmaculada S anchez-Mach in, MD, Paloma Poza, Ruperto Gonz alez, Victor Matheu, MD; Hospital Ofra-T orax, Tenerife, Spain, Hospital Ofra-T orax, santa cruz de tenerife, Spain, Hospital Ofra-T orax, S/C de Tenerife, Spain, Hospital Ofra, Tenerife, Spain. RATIONALE: Allergen sensitization appears to be part of the etiology of Atopic Dermatitis (AD). The effectiveness of allergen specific immunotherapy (SIT) in AD remains controversial, even contraindicated in severe cases. METHODS: Total IgE (T-IgE) and Specific IgE (S-IgE) by CAPFarmacia. Patient 1 (P1): 43-year-old male. Patient 2 (P2): 31-year old woman. Patient 3 (P3): 9-year-old woman. All of them were nonresponders to usual therapeutics including corticosteroids oral (Last year daily for P1, P2, and 6 cycles for P3), cyclosporin (P1, P2) or methotrexate (P1with bloody diarrhea). They hadmild persistent rhinitis and intermitent asthma and positive S-IgE to Dermatophagoidesand storage mites, and P1 also to grass, ragweed pollen and foods without clinical relevance. RESULTS: In a first visit SCORAD and T-IgEwere: P1, 81 and 31,090UI/ ml. P2, 75 and 19,038UI/ml. P3, 36 and 14.897UI/ml.We started treatment with SIT, with cluster administration schedule of 4weeks in Hospital Immunotherapy Unit and subsequent monthly maintenance. The early months P1 and P2 showed improvement. The T-IgE was descending in improved patients to be in the 4 year of SIT: 5,560UI/ml for P1 and 2,500UI/ml for P2 with SCORAD of 11 and 5 respectively. However, since there was no clinical improvement for P3 over the first year and her T-IgE increase to 19,239UI/ml and SCORAD to 40, the SIT was stopped. CONCLUSIONS:Wehave observed a rapid onset of action after initiation of SIT in some cases of Severe AD. Clinical improvement was correlated with the decrease in T-IgE. The SIT may be a therapeutic alternative.

No association between genetic ancestry and susceptibility to asthma or atopy in Canary Islanders.

Asthma is a complex respiratory disease characterized by chronic inflammation of airways and frequently associated with atopic symptoms. The population from the Canary Islands, which has resulted from a recent admixture of North African and Iberian populations, shows the highest prevalence of asthma and atopic symptoms among the Spanish populations. Although environmental particularities would account for the majority of such disparity, genetic ancestry might play a role in increasing the susceptibility of asthma or atopy, as have been demonstrated in other recently African-admixed populations. Here, we aimed to explore whether genetic ancestry was associated with asthma or related traits in the Canary Islanders. For that, a total of 734 DNA samples from unrelated individuals of the GOA study, self-reporting at least two generations of ancestors from the Canary Islands (391 asthmatics and 343 controls), were successfully genotyped for 83 ancestry informative markers (AIMs), which allowed to precisely distinguishing between North African and Iberian ancestries. No association was found between genetic ancestry and asthma or related traits after adjusting by demographic variables differing among compared groups. Similarly, none of the individual AIMs was associated with asthma when results were considered in the context of the multiple comparisons performed (0.005 ≤ p value ≤ 0.042; 0.221 ≤ q value ≤ 0.443). Our results suggest that if genetic ancestry were involved in the susceptibility to asthma or related traits among Canary Islanders, its effects would be modest. Larger studies, examining more genetic variants, would be needed to explore such possibility.