Kathleen E Sullivan

The Children's Hospital of Philadelphia, Filadelfia, Pennsylvania, United States

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Publications (211)1020.32 Total impact

  • Acta Haematologica 11/2013; 131(3):167-169. DOI:10.1159/000353758 · 0.99 Impact Factor
  • Solrun Melkorka Maggadottir, Kathleen E. Sullivan
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    ABSTRACT: A 2-year-old boy with chromosome 22q11.2 deletion syndrome was referred for recurrent sinopulmonary infections. He was diagnosed shortly after birth by a fluorescence in situ hybridization test that was performed due to interrupted aortic arch type B. He had no hypocalcemia, and his recovery from cardiac repair was uneventful. He had difficulty feeding and gained weight slowly, but, otherwise, there were no concerns during his first year of life. At 15 months of age, he began to develop significant otitis media and bronchitis. He was hospitalized once for pneumonia at 18 months of age and has never been off antibiotics for more than 1 week since then. He has not had any previous immunologic evaluation. Recurrent sinopulmonary infections in a child with chromosome 22q11.2 deletion syndrome can have the same etiologies as in any other child. Atopy, anatomic issues, cystic fibrosis, and new environmental exposures could be considered in this setting. Early childhood can be problematic for patients with chromosome 22q11.2 deletion syndrome due to unfavorable drainage of the middle ear and sinuses. Atopy occurs at a higher frequency in 22q11.2 deletion syndrome, and these children also have a higher rate of gastroesophageal reflux and aspiration than the general population. As would be appropriate for any child who presents with recurrent infections at 2 years of age, an immunologic evaluation should be performed. In this review, we will highlight recent findings and new data on the management of children and adults with chromosome 22q11.2 deletion syndrome.
    11/2013; 1(6):589–594. DOI:10.1016/j.jaip.2013.08.003
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    ABSTRACT: The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and chronic granulomatous disease through retrospective, prospective, and cross-sectional studies. The PIDTC additionally seeks to encourage training of junior investigators, establish partnerships with European and other International colleagues, work with patient advocacy groups to promote community awareness, and conduct pilot demonstration projects. Future goals include the conduct of prospective treatment studies to determine optimal therapies for primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot projects: newborn screening for SCID in Navajo Native Americans and B-cell reconstitution in patients with SCID after hematopoietic stem cell transplantation. Ten junior investigators have received grant awards. The PIDTC Annual Scientific Workshop has brought together consortium members, outside speakers, patient advocacy groups, and young investigators and trainees to report progress of the protocols and discuss common interests and goals, including new scientific developments and future directions of clinical research. Here we report the progress of the PIDTC to date, highlights of the first 2 PIDTC workshops, and consideration of future consortium objectives.
    The Journal of allergy and clinical immunology 10/2013; DOI:10.1016/j.jaci.2013.07.052 · 11.25 Impact Factor
  • Joint, bone, spine: revue du rhumatisme 09/2013; DOI:10.1016/j.jbspin.2013.08.005 · 3.22 Impact Factor
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    ABSTRACT: To examine the effect of chemotherapy for ovarian cancer on immunologic function and to define the effect on the serologic response to the influenza vaccine. Under IRB approved protocols, patients with ovarian cancer were administered seasonal trivalent killed influenza vaccines. Peripheral blood was collected for immunologic assessments. Serum was analyzed for hemagglutination inhibition (HAI) antibody titers. Peripheral blood mononuclear cells were isolated to characterize T and B cell populations and function. Thirty-one patients were recruited: 13 in remission receiving a dendritic cell vaccine with or without a single dose of low-dose cyclophosphamide, 3 in remission not receiving treatment, and 15 undergoing standard therapy. Significant effects on T cell and B cell subset distributions were seen. Functional effects were also seen. Few patients were able to mount a 4-fold HAI antibody response. A 4-fold response was observed for H1N1 in 20%, for H3N2 in 26%, and for influenza B in 6%. Pre-existing exposure to influenza was predictive of responders. Despite CDC recommendations that patients undergoing chemotherapy receive influenza vaccine, there is little evidence to support its serologic effectiveness in this population. Patients with ovarian cancer are almost uniformly unable to mount a meaningful antibody response. These findings have serious implications for future resource allocation for both seasonal and novel pandemic influenza outbreak and understanding the immunologic deficits as a result of chemotherapy may improve patient care.
    Vaccine 09/2013; 31(46). DOI:10.1016/j.vaccine.2013.09.001 · 3.49 Impact Factor
  • Patrícia Costa-Reis, Kathleen E Sullivan
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    ABSTRACT: Genetics unquestionably contributes to systemic lupus erythematosus (SLE) predisposition, progression and outcome. Nevertheless, single-gene defects causing lupus-like phenotypes have been infrequently documented. The majority of the identified genetic SLE risk factors are, therefore, common variants, responsible for a small effect on the global risk. Recently, genome wide association studies led to the identification of a growing number of gene variants associated with SLE susceptibility, particular disease phenotypes, and antibody profiles. Further studies addressed the biological effects of these variants. In addition, the role of epigenetics has recently been revealed. These combined efforts contributed to a better understanding of SLE pathogenesis and to the characterization of clinically relevant pathways. In this review, we describe SLE-associated single-gene defects, common variants, and epigenetic changes. We also discuss the limitations of current methods and the challenges that we still have to face in order to incorporate genomic and epigenomic data into clinical practice.
    Current Rheumatology Reports 09/2013; 15(9):369. DOI:10.1007/s11926-013-0369-4 · 2.45 Impact Factor
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    ABSTRACT: OBJECTIVES:Cornelia de Lange syndrome (CdLS) is a genetic syndrome with multisystem abnormalities. Infections are a significant cause of morbidity and mortality. The goals of our study were to identify the frequency and types of infections in CdLS and to determine if underlying immunodeficiency contributes to the clinical spectrum of this syndrome.METHODS:We assessed infectious histories in 45 patients with CdLS and evaluated conventional immunologic screening tests in 27 patients. Among these 27 subjects, additional phenotypic enumeration of T-cell subsets, expression of activation markers in T cells, and production of cytokines in response to T-cell stimulants were studied in 12 CdLS subjects compared with 12 normal case control subjects.RESULTS:Recurrent infections were reported at high frequency in CdLS patients and included chronic ear infections (53%), chronic viral respiratory infections (46%), pneumonia (42%), sinus infections (33%), oral candidiasis (13%), sepsis (6%), and bacterial skin infections (4%). Full immune evaluation in 27 subjects led to identification of 9 cases of antibody deficiency syndrome in patients with severe forms of CdLS. Subjects with CdLS had decreased percentages of T regulatory cells and T follicular helper cells compared with normal control subjects (P < .05).CONCLUSIONS:This study identified for the first time a high frequency of antibody deficiency in CdLS subjects, indicating a critical need for screening and management of immunodeficiency in CdLS patients with a history of well-documented severe or recurrent infections. Furthermore, our results indicate that impaired T-cell populations may be associated with antibody deficiency in CdLS.
    PEDIATRICS 07/2013; 132(2). DOI:10.1542/peds.2012-3815 · 5.30 Impact Factor
  • Patrícia Costa-Reis, Kathleen E Sullivan
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    ABSTRACT: Chronic recurrent multifocal osteomyelitis is a rare auto-inflammatory condition that primarily affects children and adolescents. It presents with recurrent episodes of pain related to the presence of foci of sterile bone inflammation. The long bones of the lower extremities are more frequently affected and the spine can also be involved. Imaging studies, including whole-body magnetic resonance, are important for diagnosis and detection of asymptomatic lesions. Bone biopsies may be necessary to exclude other diseases, including malignancy and infections. Non-steroidal anti-inflammatory drugs cause relief of symptoms in the majority of cases. Bisphosphonates and TNF-α blockers are alternatives for patients who do not respond or who have spinal involvement.
    Journal of Clinical Immunology 05/2013; 33(6). DOI:10.1007/s10875-013-9902-5 · 2.65 Impact Factor
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    ABSTRACT: A 13 year old female presented 2 years ago with episodic CUA, marginally responsive to corticosteroids. Extensive workup was negative for hereditary angioedema, different autoimmune, rheumatological, malignant and infectious conditions. Her CUA initially responded to high dose antihistamines and LTRA but worsened, required hospitalization and was unresponsive to doxepin, accolate, dapsone, cyclosporine, methotrexate and omalizumab. Workup for sinusitis revealed CVID and after 3 IVIG infusions her angioedema resolved. A 16 year old boy with recurrent sinusitis was diagnosed with CVID at age 11 and started IVIG. 4 years later he developed CUA. Extensive workup, as for the girl, was negative. During 2 months of refractory angioedema and ICU care he did not respond to high dose antihistamines, LTRA, corticosteroids, immunomodulatory IVIG doses, icatibant, FFP, omalizumab or berinert. His flares of angioedema continue and he has a tracheostomy for airway protection.The increased incidence of autoimmune disease in CVID is well established. CUA, a common diagnosis, can occur in CVID without relation to the immunodeficiency. 25-50% of CUA patients have auto-antibodies to the high affinity IgE-receptor, however this was not found in our patients. Possibly CVID patients, being prone to autoimmune conditions, have IgG auto-antibodies triggering mast cell and/or basophil activation.
    2013 Clinical Immunology Society Annual Meeting; 04/2013
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    ABSTRACT: Human DOCK8 deficiency is associated with diffuse warts, combined immunodeficiency and malignancy. NK cells serve as an innate defense against virally infected cells and function in tumor surveillance. NK cell cytotoxicity requires reorganization of actin at the lytic NK cell immunologic synapse (IS) formed with target cells. Since DOCK8-deficient patients have severe cutaneous viral infections and malignancy, we hypothesized that NK cell function was abnormal. Ten patients with biallelic DOCK8 mutations as well as NK cell lines with stably reduced DOCK8 expression were evaluated experimentally using in vitro NK cell cytotoxicity, F-actin quantification, and high-resolution analyses of the NK cell IS. Cytolytic function was decreased in DOCK8-deficient patients and cell lines and was not corrected by IL-2 stimulation. Importantly, DOCK8 deficiency did not affect total NK cell filamentous actin content, but abrogated filamentous actin accumulation at the lytic IS. DOCK8 deficiency impairs NK cell function by blocking formation of a mature lytic IS owing to ineffective synaptic actin accumulation. This previously unappreciated defective host defense mechanism may explain the unusual susceptibility to viral infections and related cancers in DOCK8-deficient patients.
    2013 Clinical Immunology Society Annual Meeting; 04/2013
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    ABSTRACT: Dyskeratosis congenita (DC) is a multisystem disease caused by genetic mutations that result in defective telomere maintenance. Herein, we describe a 17-year-old patient with severe DC, manifested by bone marrow failure, severe immunodeficiency, and enterocolitis requiring prolonged infliximab therapy, who developed fatal hepatic failure caused by an aggressive, infiltrating hepatic angiosarcoma. Although DC patients have known increased risk of developing liver failure and multiple types of malignancy, this report is the first to describe angiosarcoma in a DC patient. Malignancy should thus be considered in the differential diagnosis of progressive liver dysfunction in DC patients.
    Journal of Pediatric Hematology/Oncology 04/2013; 36(4). DOI:10.1097/MPH.0b013e318286d4d4 · 0.96 Impact Factor
  • Journal of Clinical Immunology 04/2013; 33(3):687-687. · 2.65 Impact Factor
  • Journal of Clinical Immunology 04/2013; 33(3):671-671. · 2.65 Impact Factor
  • Kathleen E. Sullivan, Lihua Shi, Li Song
    Journal of Clinical Immunology 04/2013; 33(3):671-672. · 2.65 Impact Factor
  • Annals of the Rheumatic Diseases 02/2013; 72(Suppl 1):A12-A13. DOI:10.1136/annrheumdis-2013-203215.23 · 9.27 Impact Factor
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    ABSTRACT: BACKGROUND: Dedicator of cytokinesis 8 (DOCK8) mutations are responsible for a rare primary combined immunodeficiency syndrome associated with severe cutaneous viral infections, increased IgE levels, autoimmunity, and malignancy. Natural killer (NK) cells are essential for tumor surveillance and defense against virally infected cells. NK cell function relies on Wiskott-Aldrich syndrome protein for filamentous actin (F-actin) accumulation at the lytic NK cell immunologic synapse. DOCK8 activates cell division cycle 42, which, together with Wiskott-Aldrich syndrome protein, coordinates F-actin reorganization. Although abnormalities in T- and B-cell function have been described in DOCK8-deficient patients, the role of NK cells in this disease is unclear. OBJECTIVES: We sought to understand the role of DOCK8 in NK cell function to determine whether NK cell abnormalities explain the pathogenesis of the clinical syndrome of DOCK8 deficiency. METHODS: A cohort of DOCK8-deficient patients was assembled, and patients' NK cells, as well as NK cell lines with stably reduced DOCK8 expression, were studied. NK cell cytotoxicity, F-actin content, and lytic immunologic synapse formation were measured. RESULTS: DOCK8-deficient patients' NK cells and DOCK8 knockdown cell lines all had decreased NK cell cytotoxicity, which could not be restored after IL-2 stimulation. Importantly, DOCK8 deficiency impaired F-actin accumulation at the lytic immunologic synapse without affecting overall NK cell F-actin content. CONCLUSIONS: DOCK8 deficiency results in severely impaired NK cell function because of an inability to form a mature lytic immunologic synapse through targeted synaptic F-actin accumulation. This defect might underlie and explain important attributes of the DOCK8 deficiency clinical syndrome, including the unusual susceptibility to viral infection and malignancy.
    The Journal of allergy and clinical immunology 02/2013; 131(3). DOI:10.1016/j.jaci.2012.12.1568 · 11.25 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2013; 131(2):AB8. DOI:10.1016/j.jaci.2012.12.704 · 11.25 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2013; 131(2):AB71. DOI:10.1016/j.jaci.2012.12.917 · 11.25 Impact Factor
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    ABSTRACT: Influenza is a common respiratory pathogen. Its severity can be unpredictable, but people with chronic illness are at increased risk of severe infection, complications, and death from influenza. This review examines evidence to support various strategies to protect pediatric oncology patients from influenza-related morbidity. Influenza vaccination should be considered standard. Additional evidence-supported measures include antiviral treatment, antiviral prophylaxis, cohorting of patients, and hospital infection control measures. Data from other high-risk populations support the vaccination of family members, double-dose or high-dose vaccination, and the use of barrier methods. These measures have the potential to optimize patient outcomes because there will be fewer treatment interruptions for acute illness. These strategies can also protect patients from prolonged hospitalizations and morbidity related to influenza.
    The Oncologist 01/2013; DOI:10.1634/theoncologist.2012-0401 · 4.54 Impact Factor
  • Revue du Rhumatisme 01/2013; DOI:10.1016/j.rhum.2013.09.001

Publication Stats

5k Citations
1,020.32 Total Impact Points

Institutions

  • 1994–2015
    • The Children's Hospital of Philadelphia
      • • Department of Pediatrics
      • • Division of Human Genetics and Molecular Biology
      Filadelfia, Pennsylvania, United States
    • Johns Hopkins Medicine
      • Department of Pediatrics
      Baltimore, MD, United States
  • 1998–2014
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 2013
    • Helsinki University Central Hospital
      • Division of Infectious Diseases
      Helsinki, Southern Finland Province, Finland
  • 2000–2012
    • University of Pennsylvania
      • Perelman School of Medicine
      Philadelphia, PA, United States
  • 2007
    • University Hospital Motol
      Praha, Praha, Czech Republic
  • 2003
    • Westat
      Maryland, United States
  • 1993–2001
    • Johns Hopkins University
      • Department of Pediatrics
      Baltimore, Maryland, United States