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  • A pilot study showing a stronger H1N1 influenza vaccination response during pregnancy in women who subsequently deliver preterm JOURNAL OF REPRODUCTIVE IMMUNOLOGY Andorf, S., Bhattacharya, S., Gaudilliere, B., Shaw, G. M., Stevenson, D. K., Butte, A. J., Sirota, M. 2019; 132: 16–20
  • A pilot study showing a stronger H1N1 influenza vaccination response during pregnancy in women who subsequently deliver preterm. Journal of reproductive immunology Andorf, S., Bhattacharya, S., Gaudilliere, B., Shaw, G. M., Stevenson, D. K., Butte, A. J., Sirota, M. 2019; 132: 16–20

    Abstract

    PROBLEM: Preterm birth (PTB), or the delivery of an infant prior to 37 weeks of gestation, is a major health concern. Although a variety of social, environmental, and maternal factors have been implicated in PTB, causes of preterm labor have remained largely unknown. There is evidence of effectiveness and safety of influenza vaccination during pregnancy, however fewer studies have looked at vaccination response as an indicator of an innate host response that may be associated with adverse pregnancy outcomes. We carried out a pilot study to analyze the flu vaccine response during pregnancy of women who later deliver preterm or term.METHOD OF STUDY: We performed a secondary analysis of the individual-level data from an influenza vaccination response study (openly available from ImmPort) measured by hemagglutination inhibition assay of 91 pregnant women with term deliveries and 11 women who went on to deliver preterm. Flu vaccination responses for H1N1 and H3N2 influenza strains were compared between term and preterm deliveries.RESULTS: Women who went on to deliver preterm showed a significantly (P< 0.001) greater flu vaccine response for the H1N1 strain than women who delivered at term. The vaccine response for H3N2 was not significantly different between these two groups (P= 0.97).CONCLUSIONS: Although the sample size is limited and additional validation is required, our findings suggest an increased activation of the maternal immune system as shown by the stronger vaccination response to H1N1 in women who subsequently delivered preterm, in comparison to women who delivered at term.

    View details for PubMedID 30852461

  • A Phase 2 Randomized Controlled Multisite Study Using Omalizumab-facilitated Rapid Desensitization to Test Continued vs Discontinued Dosing in Multifood Allergic Individuals. EClinicalMedicine Andorf, S., Purington, N., Kumar, D., Long, A., O'Laughlin, K. L., Sicherer, S., Sampson, H., Cianferoni, A., Whitehorn, T. B., Petroni, D., Makhija, M., Robison, R. G., Lierl, M., Logsdon, S., Desai, M., Galli, S. J., Rael, E., Assa'ad, A., Chinthrajah, S., Pongracic, J., Spergel, J. M., Tam, J., Tilles, S., Wang, J., Nadeau, K. 2019; 7: 27–38

    Abstract

    As there is limited data on the sustainability of desensitization of multifood-oral immunotherapy (multifood-OIT), we conducted a multisite multifood-OIT study to compare the efficacy of successful desensitization with sustained dosing vs discontinued dosing after multifood-OIT.We enrolled 70 participants, aged 5-22 years with multiple food allergies confirmed by double-blind placebo-controlled food challenges (DBPCFCs). In the open-label phase of the study, all participants received omalizumab (weeks 1-16) and multi-OIT (2-5 allergens; weeks 8-30) and eligible participants (on maintenance dose of each allergen by weeks 28-29) were randomized 1:1:1 to 1 g, 300 mg, or 0 mg arms (blinded, weeks 30-36) and then tested by food challenge at week 36. Success was defined as passing 2 g food challenge to at least 2 foods in week 36.Most participants were able to reach a dose of 2 g or higher of each of 2, 3, 4, and 5 food allergens (as applicable to the participant's food allergens in OIT) in week 36 food challenges. Using an intent-to-treat analysis, we did not find evidence that a 300 mg dose was effectively different than a 1 g dose in maintaining desensitization, and both together were more effective than OIT discontinuation (0 mg dose) (85% vs 55%, P = 0.03). Fifty-five percent of the intent-to-treat participants and 69% of per protocol participants randomized to the 0 mg arm showed no objective reactivity after 6 weeks of discontinuation. Cross-desensitization was found between cashew/pistachio and walnut/pecan when only one of the foods was part of OIT. No statistically significant safety differences were found between the three arms.These results suggest that sustained desensitization after omalizumab-facilitated multi-OIT best occurs through continued maintenance OIT dosing of either 300 mg or 1 g of each food allergen as opposed to discontinuation of multi-OIT.Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Jeff and MacKenzie Bezos, NIAID AADCRC U19AI104209.ClinicalTrials.gov number, NCT02626611.

    View details for DOI 10.1016/j.eclinm.2018.12.006

    View details for PubMedID 31193674

    View details for PubMedCentralID PMC6537534

  • Proteasome-Dependent Regulation of Distinct Metabolic States During Long-Term Culture of Human iPSC-Derived Cardiomyocytes. Circulation research Ebert, A., Joshi, A. U., Andorf, S., Dai, Y., Sampathkumar, S., Chen, H., Li, Y., Garg, P., Toischer, K., Hasenfuβ, G., Mochly Rosen, D., Wu, J. C. 2019

    Abstract

    The immature presentation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is currently a challenge for their application in disease modeling, drug screening, and regenerative medicine. Long-term culture is known to achieve partial maturation of iPSC-CMs. However, little is known about the molecular signaling circuitries that govern functional changes, metabolic output, and cellular homeostasis during long-term culture of iPSC-CMs.We aimed to identify and characterize critical signaling events that control functional and metabolic transitions of cardiac cells during developmental progression, as recapitulated by long-term culture of iPSC-CMs.We combined transcriptomic sequencing with pathway network mapping in iPSC-CMs that were cultured until a late time point, day 200 (D200), in comparison to a medium time point, day 90 (D90), and an early time point, day 30 (D30). Transcriptomic landscapes of long-term cultured iPSC-CMs allowed mapping of distinct metabolic stages during development of maturing iPSC-CMs. Temporally divergent control of mitochondrial metabolism was found to be regulated by cAMP/protein kinase A (PKA)- and proteasome-dependent signaling events. The PKA/proteasome-dependent signaling cascade was mediated downstream by heat shock protein 90 (Hsp90), which in turn modulated mitochondrial respiratory chain proteins and their metabolic output. During long-term culture, this circuitry was found to initiate upregulation of iPSC-CM metabolism, resulting in increased cell contractility that reached a maximum at the D200 time point.Our results reveal a PKA/proteasome- and Hsp90-dependent signaling pathway that regulates mitochondrial respiratory chain proteins and determines cardiomyocyte energy production and functional output. These findings provide deeper insight into signaling circuitries governing metabolic homeostasis in iPSC-CMs during developmental progression.

    View details for DOI 10.1161/CIRCRESAHA.118.313973

    View details for PubMedID 31104567

  • Analysis of a Large Standardized Food Challenge Data Set to Determine Predictors of Positive Outcome Across Multiple Allergens FRONTIERS IN IMMUNOLOGY Sindher, S., Long, A. J., Purington, N., Chollet, M., Slatkin, S., Andorf, S., Tupa, D., Kumar, D., Woch, M. A., O'Laughlin, K. L., Assaad, A., Pongracic, J., Spergel, J. M., Tam, J., Tilles, S., Wang, J., Galli, S. J., Nadeau, K. C., Chinthrajah, R. 2018; 9
  • Eliciting Dose and Safety Outcomes From a Large Dataset of Standardized Multiple Food Challenges FRONTIERS IN IMMUNOLOGY Purington, N., Chinthrajah, R., Long, A., Sindher, S., Andorf, S., O'Laughlin, K., Woch, M. A., Scheiber, A., Assa'ad, A., Pongracic, J., Spergel, J. M., Tam, J., Tilles, S., Wang, J., Galli, S. J., Desai, M., Nadeau, K. C. 2018; 9
  • MetaCyto: A Tool for Automated Meta-analysis of Mass and Flow Cytometry Data CELL REPORTS Hu, Z., Jujjavarapu, C., Hughey, J. J., Andorf, S., Lee, H., Gherardini, P., Spitzer, M. H., Thomas, C. G., Campbell, J., Dunn, P., Wiser, J., Kidd, B. A., Dudley, J. T., Nolan, G. P., Bhattacharya, S., Butte, A. J. 2018; 24 (5): 1377–88

    Abstract

    While meta-analysis has demonstrated increased statistical power and more robust estimations in studies, the application of this commonly accepted methodology to cytometry data has been challenging. Different cytometry studies often involve diverse sets of markers. Moreover, the detected values of the same marker are inconsistent between studies due to different experimental designs and cytometer configurations. As a result, the cell subsets identified by existing auto-gating methods cannot be directly compared across studies. We developed MetaCyto for automated meta-analysis of both flow and mass cytometry (CyTOF) data. By combining clustering methods with a silhouette scanning method, MetaCyto is able to identify commonly labeled cell subsets across studies, thus enabling meta-analysis. Applying MetaCyto across a set of ten heterogeneous cytometry studies totaling 2,926 samples enabled us to identify multiple cell populations exhibiting differences in abundance between demographic groups. Software is released to the public through Bioconductor (http://bioconductor.org/packages/release/bioc/html/MetaCyto.html).

    View details for PubMedID 30067990

  • Development of a tool predicting severity of allergic reaction during peanut challenge. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology Chinthrajah, R. S., Purington, N., Andorf, S., Rosa, J. S., Mukai, K., Hamilton, R., Smith, B. M., Gupta, R., Galli, S. J., Desai, M., Nadeau, K. C. 2018

    Abstract

    BACKGROUND: Reliable prognostic markers for predicting severity of allergic reactions during oral food challenges (OFC) have not been established.OBJECTIVE: We sought to develop a predictive algorithm of a food challenge severity score (CSS) to identify those at higher risk for severe reactions to a standardized peanut OFC.METHODS: Medical history and allergy tests were obtained for 120 peanut-allergic participants who underwent double-blind, placebo-controlled food challenges (DBPCFCs). Reactions were assigned a CSS between 1 to 6 based on cumulative tolerated dose and a "severity clinical indicator." Demographic characteristics, clinical features, peanut component IgE values, and a basophil activation marker were considered in a multi-step analysis to derive a flexible decision rule to understand risk during peanut of OFC.RESULTS: 18.3% participants had a severe reaction (CSS >4). The decision rule identified the following three variables (in order of importance) as predictors of reaction severity: ratio of %CD63hi stimulation with peanut to %CD63hi anti-IgE (CD63 ratio), history of exercise-induced asthma, and forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC) ratio. The CD63 ratio alone was a strong predictor of CSS (p<0.001).CONCLUSION: The CSS is a novel tool that combines dose thresholds and allergic reactions to understand risks associated with peanut OFCs. Lab-values (CD63 ratio), along with clinical variables (exercise-induced asthma and FEV1/FVC ratio) contribute to the predictive ability of the severity of reaction to peanut OFC. Further testing of this decision rule is needed in a larger external data source before it can be considered outside of research settings.

    View details for PubMedID 29709643

  • High dimensional immune biomarkers demonstrate differences in phenotypes and endotypes in food allergy and asthma. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology Chinthrajah, R. S., Purington, N., Sampath, V., Andorf, S., Manohar, M., Prunicki, M., Zhou, X., Tupa, D., Nadeau, K. C. 2018

    View details for PubMedID 29705381

  • Epigenetic Changes in Immune Cells Following Successful Desensitization with Multi-Food Allergen Oral Immunotherapy Chinthrajah, S., Andorf, S., Manohar, M., Maecker, H., Tsai, M., Galli, S., Nadeau, K. SPRINGER/PLENUM PUBLISHERS. 2018: 358–59
  • Anti-IgE treatment with oral immunotherapy in multifood allergic participants: a double-blind, randomised, controlled trial LANCET GASTROENTEROLOGY & HEPATOLOGY Andorf, S., Purington, N., Block, W. M., Long, A. J., Tupa, D., Brittain, E., Spergel, A., Desai, M., Galli, S. J., Nadeau, K. C., Chinthrajah, R. 2018; 3 (2): 85–94

    Abstract

    Despite progress in single food oral immunotherapy, there is little evidence concerning the safety and efficacy of treating individuals with multiple food (multifood) allergies. We did a pilot study testing whether anti-IgE (omalizumab) combined with multifood oral immunotherapy benefited multifood allergic patients.We did a blinded, phase 2 clinical trial at Stanford University. We enrolled participants, aged 4-15 years, with multifood allergies validated by double-blind, placebo-controlled food challenges to their offending foods. Inclusion criteria included a positive skin prick test of 6 mm or more (wheal diameter, above the negative control), a food-specific serum IgE concentration of more than 4 kU/L for each food, or both, and a positive double-blind, placebo-controlled food challenge at 500 mg or less of food protein. Exclusion criteria included eosinophilic oesophagitis and severe asthma. Participants were randomised (3:1) with a block size of four, to receive multifood oral immunotherapy to two to five foods, together with omalizumab (n=36) or placebo (n=12). 12 individuals who fulfilled the same inclusion and exclusion criteria were included as controls. These individuals were not randomised and received neither omalizumab nor oral immunotherapy. Omalizumab or placebo was administered subcutaneously for 16 weeks, with oral immunotherapy starting at week 8, and was stopped 20 weeks before the exit double-blind, placebo-controlled food challenge at week 36. The primary endpoint was the proportion of participants who passed double-blind, placebo-controlled food challenges to at least two of their offending foods. This completed trial is registered with ClinicalTrials.gov, number NCT02643862.Between March 25, 2015, and Aug 18, 2016, 165 participants were assessed for eligibility, of whom 84 did not meet the inclusion criteria and 21 declined to participate. We enrolled and randomised 48 eligible participants and the remaining 12 patients were included as nonrandomised, untreated controls. At week 36, a significantly greater proportion of the omalizumab-treated (30 [83%] of 36) versus placebo (four [33%] of 12) participants passed double-blind, placebo-controlled food challenges to 2 g protein for two or more of their offending foods (odds ratio 10·0, 95% CI 1·8-58·3, p=0·0044). All participants completed the study. There were no serious or severe (grade 3 or worse) adverse events. Participants in the omalizumab group had a significantly lower median per-participant percentage of oral immunotherapy doses associated with any adverse events (27% vs 68%; p=0·0082). The most common adverse events in both groups were gastrointestinal events.In multifood allergic patients, omalizumab improves the efficacy of multifood oral immunotherapy and enables safe and rapid desensitisation.US National Institutes of Health (NIH).

    View details for PubMedID 29242014

  • Food allergy and omics. The Journal of allergy and clinical immunology Dhondalay, G. K., Rael, E., Acharya, S., Zhang, W., Sampath, V., Galli, S. J., Tibshirani, R., Boyd, S. D., Maecker, H., Nadeau, K. C., Andorf, S. 2018; 141 (1): 20–29

    Abstract

    Food allergy (FA) prevalence has been increasing over the last few decades and is now a global health concern. Current diagnostic methods for FA result in a high number of false-positive results, and the standard of care is either allergen avoidance or use of epinephrine on accidental exposure, although currently with no other approved treatments. The increasing prevalence of FA, lack of robust biomarkers, and inadequate treatments warrants further research into the mechanism underlying food allergies. Recent technological advances have made it possible to move beyond traditional biological techniques to more sophisticated high-throughput approaches. These technologies have created the burgeoning field of omics sciences, which permit a more systematic investigation of biological problems. Omics sciences, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, and exposomics, have enabled the construction of regulatory networks and biological pathway models. Parallel advances in bioinformatics and computational techniques have enabled the integration, analysis, and interpretation of these exponentially growing data sets and opens the possibility of personalized or precision medicine for FA.

    View details for PubMedID 29307411

  • Eliciting Dose and Safety Outcomes From a Large Dataset of Standardized Multiple Food Challenges. Frontiers in immunology Purington, N., Chinthrajah, R. S., Long, A., Sindher, S., Andorf, S., O'Laughlin, K., Woch, M. A., Scheiber, A., Assa'ad, A., Pongracic, J., Spergel, J. M., Tam, J., Tilles, S., Wang, J., Galli, S. J., Desai, M., Nadeau, K. C. 2018; 9: 2057

    Abstract

    Background: Food allergy prevalence has continued to rise over the past decade. While studies have reported threshold doses for multiple foods, large-scale multi-food allergen studies are lacking. Our goal was to identify threshold dose distributions and predictors of severe reactions during blinded oral food challenges (OFCs) in multi-food allergic patients. Methods: A retrospective chart review was performed on all Stanford-initiated clinical protocols involving standardized screening OFCs to any of 11 food allergens at 7 sites. Interval-censoring survival analysis was used to calculate eliciting dose (ED) curves for each food. Changes in severity and ED were also analyzed among participants who had repeated challenges to the same food. Results: Of 428 participants, 410 (96%) had at least one positive challenge (1445 standardized OFCs with 1054 total positive challenges). Participants undergoing peanut challenges had the highest ED50 (29.9 mg), while those challenged with egg or pistachio had the lowest (7.07 or 1.7 mg, respectively). The most common adverse event was skin related (54%), followed by gastrointestinal (GI) events (33%). A history of asthma was associated with a significantly higher risk of a severe reaction (hazard ratio [HR]: 2.37, 95% confidence interval [CI]: 1.36, 4.13). Higher values of allergen-specific IgE (sIgE) and sIgE to total IgE ratio (sIgEr) were also associated with higher risk of a severe reaction (1.49 [1.19, 1.85] and 1.84 [1.30, 2.59], respectively). Participants undergoing cashew, peanut, pecan, sesame, and walnut challenges had more severe reactions as ED increased. In participants who underwent repeat challenges, the ED did not change (p = 0.66), but reactions were more severe (p = 0.02). Conclusions: Participants with a history of asthma, high sIgEr, and/or high values of sIgE were found to be at higher risk for severe reactions during food challenges. These findings may help to optimize food challenge dosing schemes in multi-food allergic, atopic patients, specifically at lower doses where the majority of reactions occur. Trials Registration Number: ClinicalTrials. gov number NCT03539692; https://clinicaltrials.gov/ct2/show/NCT03539692.

    View details for PubMedID 30298065

  • Analysis of a Large Standardized Food Challenge Data Set to Determine Predictors of Positive Outcome Across Multiple Allergens. Frontiers in immunology Sindher, S., Long, A. J., Purington, N., Chollet, M., Slatkin, S., Andorf, S., Tupa, D., Kumar, D., Woch, M. A., O'Laughlin, K. L., Assaad, A., Pongracic, J., Spergel, J. M., Tam, J., Tilles, S., Wang, J., Galli, S. J., Nadeau, K. C., Chinthrajah, R. S. 2018; 9: 2689

    Abstract

    Background: Double-blind placebo-controlled food challenges (DBPCFCs) remain the gold standard for the diagnosis of food allergy; however, challenges require significant time and resources and place the patient at an increased risk for severe allergic adverse events. There have been continued efforts to identify alternative diagnostic methods to replace or minimize the need for oral food challenges (OFCs) in the diagnosis of food allergy. Methods: Data was extracted for all IRB-approved, Stanford-initiated clinical protocols involving standardized screening OFCs to a cumulative dose of 500 mg protein to any of 11 food allergens in participants with elevated skin prick test (SPT) and/or specific IgE (sIgE) values to the challenged food across 7 sites. Baseline population characteristics, biomarkers, and challenge outcomes were analyzed to develop diagnostic criteria predictive of positive OFCs across multiple allergens in our multi-allergic cohorts. Results: A total of 1247 OFCs completed by 427 participants were analyzed in this cohort. Eighty-five percent of all OFCs had positive challenges. A history of atopic dermatitis and multiple food allergies were significantly associated with a higher risk of positive OFCs. The majority of food-specific SPT, sIgE, and sIgE/total IgE (tIgE) thresholds calculated from cumulative tolerated dose (CTD)-dependent receiver operator curves (ROC) had high discrimination of OFC outcome (area under the curves > 0.75). Participants with values above the thresholds were more likely to have positive challenges. Conclusions: This is the first study, to our knowledge, to not only adjust for tolerated allergen dose in predicting OFC outcome, but to also use this method to establish biomarker thresholds. The presented findings suggest that readily obtainable biomarker values and patient demographics may be of use in the prediction of OFC outcome and food allergy. In the subset of patients with SPT or sIgE values above the thresholds, values appear highly predictive of a positive OFC and true food allergy. While these values are relatively high, they may serve as an appropriate substitute for food challenges in clinical and research settings.

    View details for PubMedID 30538699

  • Observational long-term follow-up study of rapid food oral immunotherapy with omalizumab ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY Andorf, S., Manohar, M., Dominguez, T., Block, W., Tupa, D., Kshirsagar, R. A., Sampath, V., Chinthrajah, R., Nadeau, K. C. 2017; 13: 51

    Abstract

    A number of clinical studies focused on treating a single food allergy through oral immunotherapy (OIT) with adjunctive omalizumab treatment have been published. We previously demonstrated safety and tolerability of a rapid OIT protocol using omalizumab in a phase 1 study to achieve desensitization to multiple (up to 5) food allergens in parallel, rapidly (7-36 weeks; median = 18 weeks). In the current long-term, observational study, we followed 34 food allergic participants for over 5 years, who had originally undergone the phase 1 rapid OIT protocol.After reaching the maintenance dose of 2 g protein for each of their respective food allergens as a part of the phase 1 study, the long-term maintenance dose was reduced for some participants based on a pragmatic team-based decision. Participants were followed up to 62 months through standard oral food challenges (OFCs), skin prick tests, and blood tests.Each participant passed the 2 g OFC to each of their offending food allergens (up to 5 food allergens in total) at the end of the long-term follow-up (LTFU) study.Our data demonstrate the feasibility of long-term maintenance dosing of a food allergen without compromising the desensitized status conferred through rapid-OIT. Trial registration Registry: Clinicaltrials.gov. Registration numbers: NCT01510626 (original study), NCT03234764 (LTFU study). Date of registration: November 29, 2011 (original study); July 26, 2017 (LTFU study, retrospectively registered).

    View details for PubMedID 29296107

    View details for PubMedCentralID PMC5738812

  • Feasibility of sustained response through long-term dosing in food allergy immunotherapy ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY Andorf, S., Manohar, M., Dominguez, T., Block, W., Tupa, D., Kshirsagar, R. A., Sampath, V., Chinthrajah, R., Nadeau, K. C. 2017; 13: 52

    Abstract

    Clinical trials using oral immunotherapy (OIT) for the treatment of food allergies have shown promising results. We previously demonstrated the feasibility of desensitization for up to 5 food allergens simultaneously through OIT. In this observational study, we report the findings of long-term follow-up (LTFU) of the participants treated through a single site OIT phase 1 trial.The participants (n = 46) were followed up to 72 months since the time they reached 2 g maintenance dose per food in the initial phase 1 trial. During the long-term maintenance dosing, participants continued or reduced the initial maintenance dose of food allergen protein to high (median 2 g protein) vs. low (median 300 mg protein). Participant follow-up included clinical monitoring, standardized OFCs, and in some cases, skin prick tests and measurement of allergen-specific IgE and IgG4.Irrespective of the high vs. low long-term maintenance dose during LTFU, all participants were able to ingest 2 g protein of each food allergen protein during OFCs performed at the end of our LTFU.Our LTFU cohort of food OIT participants from a single site, phase 1 OIT study, supports the feasibility of sustained desensitization through long-term maintenance dosing. Trial registration Registry: Clinicaltrial.gov. Registration numbers: NCT01490177 (original study); NCT03234764 (LTFU study). Date of registration: November 29, 2011 (original study); July 26, 2017 (LTFU study, registered).

    View details for PubMedID 29296108

    View details for PubMedCentralID PMC5738818

  • Oral immunotherapy for food allergy SEMINARS IN IMMUNOLOGY Freeland, D., Manohar, M., Andorf, S., Hobson, B. D., Zhang, W., Nadeau, K. C. 2017; 30: 36–44

    Abstract

    Food allergy is a pathological, potentially deadly cascade of immune responses to molecules or molecular fragments that are normally innocuous when encountered in foods, such as milk, egg, or peanut. As the incidence and prevalence of food allergy rise, the standard of care is poised to advance beyond food allergen avoidance coupled with injectable epinephrine treatment of allergen-induced systemic reactions. Recent studies provide evidence that oral immunotherapy may effectively redirect the atopic immune responses of food allergy patients as they ingest small but gradually increasing allergen doses over many months, eliciting safer immune responses to these antigens. Research into the molecular and cellular bases of pathological and therapeutic immune responses, and into the possibilities for their safe and effective modulation, is generating tremendous interest in basic and clinical immunology. We synthesize developments, innovations, and key challenges in our understanding of the immune mechanisms associated with atopy and oral immunotherapy for food allergy.

    View details for PubMedID 28865877

    View details for PubMedCentralID PMC5776738

  • Association of Clinical Reactivity with Sensitization to Allergen Components in Multifood-Allergic Children. journal of allergy and clinical immunology. In practice Andorf, S., Borres, M. P., Block, W., Tupa, D., Bollyky, J. B., Sampath, V., Elizur, A., Lidholm, J., Jones, J. E., Galli, S. J., Chinthrajah, R. S., Nadeau, K. C. 2017

    Abstract

    Thirty percent of children with food allergies have multiple simultaneous allergies; however, the features of these multiple allergies are not well characterized serologically or clinically.We comprehensively evaluated 60 multifood-allergic patients by measuring serum IgE to key allergen components, evaluating clinical histories and medication use, performing skin tests, and conducting double-blind, placebo-controlled food challenges (DBPCFCs).Sixty participants with multiple food allergies were characterized by clinical history, DBPCFCs, total IgE, specific IgE, and component-resolved diagnostics (IgE and IgG4) data. The food allergens tested were almond, egg, milk, sesame, peanut, pecan, walnut, hazelnut, cashew, pistachio, soy, and wheat.Our data demonstrate that of the reactions observed during a graded DBPCFC, gastrointestinal reactions occurred more often in boys than in girls, as well as in individuals with high levels of IgE to 2S albumins from cashew, walnut, and hazelnut. Certain food allergies often occurred concomitantly in individuals (ie, cashew/pistachio and walnut/pecan/hazelnut). IgE testing to components further corroborated serological relationships between and among these clustered food allergies.Associations of certain food allergies were shown by DBPCFC outcomes as well as by correlations in IgE reactivity to structurally related food allergen components. Each of these criteria independently demonstrated a significant association between allergies to cashew and pistachio, as well as among allergies to walnut, pecan, and hazelnut.

    View details for DOI 10.1016/j.jaip.2017.01.016

    View details for PubMedID 28351786

  • RImmPort: an R/Bioconductor package that enables ready-for-analysis immunology research data. Bioinformatics Shankar, R. D., Bhattacharya, S., Jujjavarapu, C., Andorf, S., Wiser, J. A., Butte, A. J. 2017

    Abstract

    : Open access to raw clinical and molecular data related to immunological studies has created a tremendous opportunity for data-driven science. We have developed RImmPort that prepares NIAID-funded research study datasets in ImmPort (immport.org) for analysis in R. RImmPort comprises of three main components: (i) a specification of R classes that encapsulate study data, (ii) foundational methods to load data of a specific study and (iii) generic methods to slice and dice data across different dimensions in one or more studies. Furthermore, RImmPort supports open formalisms, such as CDISC standards on the open source bioinformatics platform Bioconductor, to ensure that ImmPort curated study datasets are seamlessly accessible and ready for analysis, thus enabling innovative bioinformatics research in immunology.RImmPort is available as part of Bioconductor (bioconductor.org/packages/RImmPort).rshankar@stanford.edu.Supplementary data are available at Bioinformatics online.

    View details for DOI 10.1093/bioinformatics/btw719

    View details for PubMedID 28057685

  • Temporal Regulation by Innate Type 2 Cytokines in Food Allergies. Current allergy and asthma reports Graham, M. T., Andorf, S., Spergel, J. M., Chatila, T. A., Nadeau, K. C. 2016; 16 (10): 75-?

    Abstract

    Food allergies (FAs) are a growing epidemic in western countries with poorly defined etiology. Defined as an adverse immune response to common food allergens, FAs present heterogeneously as a single- or multi-organ response that ranges in severity from localized hives and angioedema to systemic anaphylaxis.Current research focusing on epithelial-derived cytokines contends that temporal regulation by these factors impact initial sensitization and persistence of FA responses upon repeated food allergen exposure. Mechanistic understanding of FA draws insight from a myriad of atopic conditions studied in humans and modeled in mice. In this review, we will highlight how epithelial-derived cytokines initiate and then potentiate FAs. We will also review existing evidence of the contribution of other atopic diseases to FA pathogenesis and whether FA symptoms overlap with other atopic diseases.

    View details for PubMedID 27771884

  • T-Cell Immunophenotyping of Second-Hand Smoke-related Asthma. Annals of the American Thoracic Society Bauer, R. N., Chinthrajah, R. S., Andorf, S., Hobson, B., Miller, R. L., Nadeau, K. C. 2016; 13: S95-?

    View details for DOI 10.1513/AnnalsATS.201507-457MG

    View details for PubMedID 27027962

  • ImmPort: disseminating data to the public for the future of immunology. Immunologic research Bhattacharya, S., Andorf, S., Gomes, L., Dunn, P., Schaefer, H., Pontius, J., Berger, P., Desborough, V., Smith, T., Campbell, J., Thomson, E., Monteiro, R., Guimaraes, P., Walters, B., Wiser, J., Butte, A. J. 2014; 58 (2-3): 234-239

    Abstract

    The immunology database and analysis portal (ImmPort) system is the archival repository and dissemination vehicle for clinical and molecular datasets created by research consortia funded by the National Institute of Allergy and Infectious Diseases Division of Allergy, Immunology, and Transplantation. With nearly 100 datasets now publicly available and hundreds of downloads per month, ImmPort is an important source for raw data and protocols from clinical trials, mechanistic studies, and novel methods for cellular and molecular measurements. To facilitate data transfer, templates for data representation and standard operating procedures have also been created and are also publicly available. ImmPort facilitates transparency and reproducibility in immunology research, serves as an important resource for education, and enables newly generated hypotheses and data-driven science.

    View details for DOI 10.1007/s12026-014-8516-1

    View details for PubMedID 24791905