Maria Garcia-Lloret

University of California, Los Angeles, Los Ángeles, California, United States

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Publications (21)160.33 Total impact

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    ABSTRACT: Traffic-related particulate matter (PM) has been linked to a heightened incidence of asthma and allergic diseases. However, the molecular mechanisms by which PM exposure promotes allergic diseases remain elusive. We sought to determine the expression, function, and regulation of pathways involved in promotion of allergic airway inflammation by PM. We used gene expression transcriptional profiling, in vitro culture assays, and in vivo murine models of allergic airway inflammation. We identified components of the Notch pathway, most notably Jagged 1 (Jag1), as targets of PM induction in human monocytes and murine dendritic cells. PM, especially ultrafine particles, upregulated TH cytokine levels, IgE production, and allergic airway inflammation in mice in a Jag1- and Notch-dependent manner, especially in the context of the proasthmatic IL-4 receptor allele Il4raR576. PM-induced Jag1 expression was mediated by the aryl hydrocarbon receptor (AhR), which bound to and activated AhR response elements in the Jag1 promoter. Pharmacologic antagonism of AhR or its lineage-specific deletion in CD11c(+) cells abrogated the augmentation of airway inflammation by PM. PM activates an AhR-Jag1-Notch cascade to promote allergic airway inflammation in concert with proasthmatic alleles. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    The Journal of allergy and clinical immunology 03/2015; 136(2). DOI:10.1016/j.jaci.2015.02.014 · 11.48 Impact Factor
  • Bob Geng · Maria Garcia-Lloret · Deborah McCurdy · Eric Yen · Tanesha Moss ·

    Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB14. DOI:10.1016/j.jaci.2014.12.978 · 11.48 Impact Factor
  • Moira E. Breslin · Maria Garcia-Lloret · Melinda Braskett ·

    Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB124. DOI:10.1016/j.jaci.2014.12.1338 · 11.48 Impact Factor
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    ABSTRACT: In the United States, newborn screening (NBS) is currently recommended for identification of 31 debilitating and potentially fatal conditions. However, individual states determine which of the recommended conditions are screened. The addition of severe combined immunodeficiency (SCID) screening to the recommended NBS panel has been fully instituted by 18 states, with another 11 states piloting programs or planning to begin screening in 2014. Untreated, SCID is uniformly fatal by 2 years of age. Hematopoietic stem cell transplantation usually is curative, but the success rate depends on the age at which the procedure is performed. Short-term implementation costs may be a barrier to adding SCID to states' NBS panels. A retrospective economic analysis was performed to determine the cost-effectiveness of NBS for early (<3.5 months) versus late (≥3.5 months) treatment of children with SCID at 3 centers over 5 years. The mean total charges at these centers for late treatment were 4 times greater than early treatment ($1.43 million vs $365,785, respectively). Mean charges for intensive care treatments were >5 times higher ($350,252 vs $66,379), and operating room–anesthesia charges were approximately 4 times higher ($57,105 vs $15,885). The cost-effectiveness of early treatment for SCID provides a strong economic rationale for the addition of SCID screening to NBS programs of other states.
    08/2014; 2(6). DOI:10.1016/j.jaip.2014.05.013

  • Journal of Allergy and Clinical Immunology 02/2014; 133(2):AB95. DOI:10.1016/j.jaci.2013.12.355 · 11.48 Impact Factor
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    ABSTRACT: The generation of oxidative stress by ambient air pollution particles contributes to the development of allergic sensitization and asthma, as demonstrated by intranasal challenge with well-characterized diesel exhaust particle (DEP) suspensions in humans. This effect is due to the presence of redox active organic chemicals in DEP, and can be suppressed by antioxidants and inducers of phase II enzymes in animals. In this communication, we determined whether the administration of a standardized broccoli sprout extract (BSE), which contains a reproducible amount of the sulforaphane (SFN) precursor, glucoraphanin, could be used to suppress the nasal inflammatory response in human subjects challenged with 300 μg of an aqueous DEP suspension (equivalent to daily PM exposure levels on a Los Angeles freeway). SFN is capable of inducing an antioxidant and phase II response via activation of the nuclear transcription factor (erythroid-derived 2)-like 2 (Nrf2). Previous studies have shown that 70-90% SFN delivered by BSE is absorbed, metabolized, and excreted in humans. An initial intranasal challenge with DEP in 29 human subjects was used to characterize the magnitude of the inflammatory response. Following a 4 week washout, a BSE that delivers a reproducible and standardized dose of 100 μmol SFN in mango juice was administered daily for four days. The nasal DEP challenge was repeated and lavage fluid collected to perform white blood cell (WBC) counts. The average nasal WBC increased by 66% over the initial screening levels and by 85% over the control levels 24 hours after DEP exposure. However, total cell counts decreased by 54% when DEP challenge was preceded by daily BSE administration for 4 days (p < 0.001). Since the SFN dose in these studies is equivalent to the consumption of 100-200 g broccoli, our study demonstrates the potential preventive and therapeutic potential of broccoli or broccoli sprouts rich in glucoraphanin for reducing the impact of particulate pollution on allergic disease and asthma.
    11/2013; 5(8). DOI:10.1039/c3fo60277j
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    ABSTRACT: : Cutaneous granulomas with prominent caseating necrosis are a rare manifestation of immunodeficiency. Extensive and recalcitrant cutaneous viral infections can also be seen. We present a case of an 18-year-old white man with an early onset poorly characterized combined immunodeficiency syndrome who, over the past 5 years, developed enlarging tender red-purple plaques on his extremities and pink near-confluent macules on his chest and back. Previous biopsies of the red-purple plaques showed features of granuloma annulare. Histopathological examination of old and new biopsies revealed both sarcoidal and palisading necrobiotic granulomas with perforating features and elastophagocytosis. Stains and tissue cultures were negative for bacterial and fungal organisms. In addition, biopsy of a macule on the back demonstrated verruca plana with characteristics of epidermodysplasia verruciformis. As an infant, the patient had failure to thrive and a combined immunodeficiency, but was lost to follow-up for 15 years. He currently continues to have severe hypogammaglobinemia and cellular immunodeficiency. Intravenous immunoglobulin and prednisone were initiated and his plaques improved rapidly. Topical imiquimod was ineffective for the verruca plana. The patient and his parents are currently undergoing whole exome sequencing including evaluation for epidermodysplasia verruciformis 1 and 2 gene mutations. This case highlights the importance of including genetic immunodeficiency disorders in the clinical and histopathological differential diagnosis for cutaneous sarcoidal or palisading necrobiotic granulomas and for extensive cutaneous viral infection.
    The American Journal of dermatopathology 11/2013; 36(2). DOI:10.1097/DAD.0b013e3182a67f9b · 1.39 Impact Factor
  • Bob Geng · Gary Rachelefsky · Maria Garcia-Lloret · Gerald C. Berkman ·
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    ABSTRACT: IgA plays crucial part of mucosal host defense. IgA deficiency is most common primary immunodeficiency. Strongyloidiasis is uncommon for non-immigrants in California. This is only 2nd published case of Strongyloidiasis with IgA deficiency raising question of significance of IgA in anti-helminthic immunity. 9 year old boy presented with sore throat and malaise. Labs over next 2 months showed eosinophilia (2200cells/mL), elevated IgE (6426 IU/ml) and IgA deficiency (<15mg/dL). IgA by additional assay was 0.1mg/dL. Generalized symptoms resolved but developed 2 episodes of vomiting and diarrhea over next several months. Allergy tests were unremarkable, and he did not have asthma or eczema. 3 ova & parasite stool studies were negative. While eosinophilia waxed and waned, levels reached 6926cells/mL prompting assay for serum Strongyloides antibody that was positive. Following which, 4th stool study revealed Charcot Leyden crystals and Strongyloides larva. Patient born in US, and had no recent foreign travel. Strongyloides can persist in hosts for decades. Disease acquisition and progression in “immunocompetent” patients are poorly understood. Infected humans produce Strongyloides specific IgA, and IgA is associated with parasite immunology in certain animals. This case of IgA deficient patient in non-endemic population suggests IgA may play role in anti-parasite host defense.
    2013 Clinical Immunology Society Annual Meeting; 04/2013
  • Bob Geng · Gary Rachelefsky · Maria Garcia-Lloret · Gerald C. Berkman ·

    Journal of Clinical Immunology 04/2013; 33(3):697-697. · 3.18 Impact Factor
  • Caroline Kuo · E. Richard Stiehm · Maria Garcia-Lloret ·

    Journal of Allergy and Clinical Immunology 02/2013; 131(2):AB71. DOI:10.1016/j.jaci.2012.12.916 · 11.48 Impact Factor
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    Journal of Allergy and Clinical Immunology 02/2011; 127(2). DOI:10.1016/j.jaci.2010.12.976 · 11.48 Impact Factor
  • M. Noval-Rivas · Y. Zhang · M. Garcia-Lloret · T. Chatila ·

    Journal of Allergy and Clinical Immunology 02/2011; 127(2). DOI:10.1016/j.jaci.2010.12.564 · 11.48 Impact Factor
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    ABSTRACT: In atopic subjects food ingestion drives the production of IgE antibodies that can trigger hypersensitivity reactions. The IL-4 pathway plays a critical role in this response, and genetic polymorphisms in its components have been linked to allergy. We sought to test whether an activating mutation in the IL-4 receptor (IL-4R) α chain enhances allergic responses to a food antigen. F709 mice, in which the IL-4Rα immunoreceptor tyrosine-based inhibitory motif is inactivated, were gavage fed with ovalbumin (OVA). Reactions to OVA challenge and immune responses, including antibody production and T(H)2 responses, were assessed. F709 mice, but not wild-type control animals, sensitized by means of gavage with OVA and either cholera toxin or staphylococcal enterotoxin B, displayed mast cell activation and systemic anaphylaxis on enteral challenge. Anaphylaxis was elicited even in F709 mice enterally sensitized with OVA alone. Bone marrow chimera experiments established that the increased sensitivity conferred by the F709 genotype was mediated mostly by hematopoietic cells but that nonhematopoietic cells also contributed. F709 mice exhibited increased intestinal permeability to macromolecules. The F709 genotype conferred increased OVA-specific IgE but not IgG1 responses, local and systemic T(H)2 responses, and intestinal mast cell hyperplasia compared with wild-type mice. Anaphylaxis was abrogated in F709 mice lacking IgE or the high-affinity receptor for IgE (FcεRI). Augmented IL-4Rα signaling confers increased intestinal permeability and dramatically enhanced sensitivity to food allergens. Unlike anaphylaxis to injected antigens, which in rodents can be mediated by either IgE or IgG antibodies, the food-induced response in F709 mice is solely IgE dependent.
    The Journal of allergy and clinical immunology 12/2010; 127(3):795-805.e1-6. DOI:10.1016/j.jaci.2010.11.009 · 11.48 Impact Factor
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    ABSTRACT: The hyper IgE syndrome (HIES) is characterized by abscesses, eczema, recurrent infections, skeletal and connective tissue abnormalities, elevated serum IgE, and diminished inflammatory responses. It exists as autosomal-dominant and autosomal-recessive forms that manifest common and distinguishing clinical features. A majority of those with autosomal-dominant HIES have heterozygous mutations in signal transducer and activator of transcription (STAT)-3 and impaired T(H)17 differentiation. To elucidate mechanisms underlying different forms of HIES. A cohort of 25 Turkish children diagnosed with HIES were examined for STAT3 mutations by DNA sequencing. Activation of STAT3 by IL-6 and IL-21 and STAT1 by IFN-alpha was assessed by intracellular staining with anti-phospho (p)STAT3 and -pSTAT1 antibodies. T(H)17 and T(H)1 cell differentiation was assessed by measuring the production of IL-17 and IFN-gamma, respectively. Six subjects had STAT3 mutations affecting the DNA binding, Src homology 2, and transactivation domains, including 3 novel ones. Mutation-positive but not mutation-negative subjects with HIES exhibited reduced phosphorylation of STAT3 in response to cytokine stimulation, whereas pSTAT1 activation was unaffected. Both patient groups exhibited impaired T(H)17 responses, but whereas STAT3 mutations abrogated early steps in T(H)17 differentiation, the defects in patients with HIES with normal STAT3 affected more distal steps. In this cohort of Turkish children with HIES, a majority had normal STAT3, implicating other targets in disease pathogenesis. Impaired T(H)17 responses were evident irrespective of the STAT3 mutation status, indicating that different genetic forms of HIES share a common functional outcome.
    The Journal of allergy and clinical immunology 09/2009; 124(2):342-8, 348.e1-5. DOI:10.1016/j.jaci.2009.05.004 · 11.48 Impact Factor
  • K. Chen · M. I. Garcia-Lloret · S. A. McGhee · S. Srikanth · Y. Gwack · E. R. B. McCabe ·

    Journal of Allergy and Clinical Immunology 02/2009; 123(2). DOI:10.1016/j.jaci.2008.12.312 · 11.48 Impact Factor
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    Maria Garcia-Lloret · Sean McGhee · Talal A Chatila ·
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    ABSTRACT: The benefit of immunoglobulin (IG) replacement in primary antibody deficiencies is unquestionable. Many of these congenital disorders present early in life and this therapy is often first implemented in the young. This article focuses on the indications of IG replacement in children, with an emphasis on the specific diagnostic problems encountered in this population. Also presented is an overview of the practical aspects of IG administration in the pediatric setting, including the recognition and management of adverse reactions. Finally, the advent of subcutaneous IG, a therapeutic IG modality with the potential to have a great impact on the quality of life of children with antibody deficiencies and their families, is discussed.
    Immunology and Allergy Clinics of North America 12/2008; 28(4):833-49, ix. DOI:10.1016/j.iac.2008.07.001 · 1.82 Impact Factor
  • Kaleo Ede · Deborah McCurdy · Maria Garcia-Lloret ·
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    ABSTRACT: Hypertrophic osteoarthropathy is an uncommon disease in the pediatric age group characterized by noninflammatory joint effusions, terminal digit clubbing, and radiographic evidence of periosteal new bone formation affecting the hands, feet, and distal limbs. The hepatopulmonary syndrome is also uncommon in childhood and presents as hepatic dysfunction, impaired arterial oxygenation, and intrapulmonary shunting. We report the case of a 17-year-old male with a history of liver transplantation at 4 months for biliary atresia who was initially diagnosed with juvenile rheumatoid arthritis but later developed features of classic hypertrophic osteoarthropathy. In addition, he was found to have the hepatopulmonary syndrome. It is important to consider hypertrophic osteoarthropathy as an imitator of juvenile rheumatoid arthritis, to recognize its known association with chronic liver disease, and to know that hepatopulmonary syndrome can occur in the setting of hypertrophic osteoarthropathy.
    Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases 09/2008; 14(4):230-3. DOI:10.1097/RHU.0b013e31817de06c · 1.08 Impact Factor
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    Talal A Chatila · Ning Li · Maria Garcia-Lloret · Hyon-Jeen Kim · Andre E Nel ·
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    ABSTRACT: Originally interpreted within the framework of a binary T(H)1/T(H)2 paradigm, our knowledge of the pathogenesis of atopic diseases has broadened to incorporate the contribution of T regulatory cells and the newly described proinflammatory T(H)17 cell lineage. The commitment of peripheral T-cell clones to undergo differentiation into one of those lineages is shaped by self-reinforcing transcriptional circuitries that center on key transcriptional regulators: T-box expressed in T cells (T(H)1), GATA-3 (T(H)2), forkhead box p3 (T regulatory cells), and retinoid-related orphan receptor gammatau/retinoid-related orphan receptor alpha (T(H)17). These circuits function both to establish the respective lineage phenotype and to enable epigenetic changes that maintain those phenotypes long-term. This evolving view of how signaling and transcriptional networks generate effector T-cell responses suggests novel therapeutic approaches to reprogram effector T-cell lineage commitment in allergic diseases in favor of tolerance induction.
    The Journal of allergy and clinical immunology 05/2008; 121(4):812-23; quiz 824-5. DOI:10.1016/j.jaci.2008.02.025 · 11.48 Impact Factor
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    ABSTRACT: Therapeutic options for DiGeorge syndrome (DGS) with profound T-cell deficiency are very limited. Thymic transplantation has shown promising results but is not easily available. Hematopoietic cell transplantation (HCT) has been successful in restoring immune competence in the short term. Present the long-term follow-up of 2 patients with complete DGS who received bone marrow transplants in the neonatal period from HLA-matched siblings, and perform a multicenter survey to document the status of other patients with DGS who have undergone HCT. Immune function assessment by immunophenotyping, lymphocyte proliferation, T-cell receptor excision circles, single nucleotide polymorphism mapping arrays, spectratyping, cytogenetics, and fluorescence in situ hybridization were used. Among reported patients with DGS receiving HCT, survival is greater than 75%. Our patients are in their 20s and in good health. Their hematopoietic compartment shows continuous engraftment with mixed chimerism, normal T-cell function, and humoral immunity. Circulating T cells exhibit a memory phenotype with a restricted repertoire and are devoid of T-cell receptor excision circles. These features suggest that T-cell reconstitution has occurred predominantly through expansion of the donors' mature T-cell pool. Although restricted, their immune systems are capable of providing substantial protection to infection and respond to vaccines. We conclude that bone marrow transplant achieves long-lived reconstitution of immune function in complete DGS and is a good alternative to thymic transplantation in patients with a suitable donor. Bone marrow transplant in complete DGS using an HLA-matched sibling donor provides long-lasting immunity and is a suitable and more available alternative to thymic transplantation.
    Journal of Allergy and Clinical Immunology 11/2007; 120(4):908-15. DOI:10.1016/j.jaci.2007.08.048 · 11.48 Impact Factor
  • M. Braskett · M. I. Garcia-Lloret · S. Howenstine · D. McCurdy · S. McGhee ·

    Journal of Allergy and Clinical Immunology 01/2007; 119(1). DOI:10.1016/j.jaci.2006.11.093 · 11.48 Impact Factor