R U Sorensen

Louisiana State University Health Sciences Center New Orleans, New Orleans, Louisiana, United States

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Publications (101)378.38 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) are effective in the treatment of patients with primary antibody deficiency disorders (PAD). The purpose of this study was to evaluate Streptococcus pneumoniae (Spn) antibody titers to 14 serotypes in patients receiving IVIG compared to SCIG and to correlate Spn antibody levels to clinical outcome. The doses of IgG/kg/month were similar in both IVIG and SCIG groups. In 11 patients treated with IVIG, Spn antibody titers were ≥1.3 mcg/ml to 99.4% ± 2.1% of the 14 serotypes at Peak IVIG but decreased to 66.9% ± 19.8% at Trough IVIG. Loss of Spn titers ≥1.3 mcg/ml was most frequent for Spn serotypes 1, 4, 9V, and 23. This correlated with lower Spn antibody titers to these serotypes at Peak IVIG compared to the other serotypes. In 13 patients treated with SCIG, Spn antibody titers were protective to 58.2% ± 23.3% of the serotypes 3-5 days after infusion, similar to Trough IVIG. Likewise the Spn serotypes with the least protective percentages were the same as the ones observed in Trough IVIG. There were no annualized serious bacterial infections (aSBI) in either group. However, there were significantly decreased annualized other infections (aOI) in the SCIG group compared to the IVIG treated group, 0.8 ± 0.7 versus 2.2 ± 1.2 infections/patient/year (P = 0.004). Breakthrough aOI did not correlate with protective or higher serum Spn antibody titers. This article is protected by copyright. All rights reserved.
    Clinical & Experimental Immunology 06/2015; DOI:10.1111/cei.12665 · 3.28 Impact Factor
  • Lily E Leiva, Hanh Monjure, Ricardo U Sorensen
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    ABSTRACT: Clinical observations in patients with specific antibody deficiency treated for periods of time with IgG infusion have suggested that IgG may have a positive immunoregulatory effect on the production of specific antibodies against pneumococcal polysaccharides. We developed an in vitro model to test the effect of an IgIV preparation on the antibody production in response to a pneumococcal polysaccharide serotype and on the antibody and cytokine production in response to both a protein antigen and a pneumococcal polysaccharide antigen. We studied 37 consecutive patients referred to our clinics for evaluation of their recurrent respiratory infections. Subjects were divided into two groups: 22 patients without SAD and 15 patients with SAD. PBMCs were left unstimulated or were stimulated with tetanus toxoid or pneumococcal polysaccharide serotype 19, in the presence of human albumin or IgIV. IgG anti-Pn-19 antibody, IL-4 and IFN-γ concentrations in culture supernatants were determined by ELISA. An increase in IgG anti-Pn-19 antibodies, associated with an increase in IFN-γ and a decrease in IL-4 production was observed in cultures stimulated with pneumococcal polysaccharide in the presence of IgIV when patients were analyzed together. The enhancing effect of IgIV was more significant for both IgG anti-Pn19 antibodies and IFN-γ in patients without SAD. In contrast, IgIV caused a significant decrease in IL-4 secretion in patients with SAD, which was associated with an increase in IgG anti-Pn19 antibodies in 3 of 7 of these patients. These results suggest that IgIV has some immunomodulatory effect on the in vitro production of IgG anti-Pn19 antibodies and cytokine production in cell cultures stimulated with Pn-19 antigen and that this modulation may be associated with a Th1/Th2 regulatory mechanism. Further studies at a cellular and molecular level are in progress to examine if the differences in the in vitro modulatory response to IgIV in these two groups of patients may point to a functional defect in patients with SAD.
    Journal of Clinical Immunology 12/2014; 35(2). DOI:10.1007/s10875-014-0120-6 · 2.65 Impact Factor
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    Ricardo U Sorensen, Lily E Leiva
    Journal of Clinical Immunology 12/2013; 34(2). DOI:10.1007/s10875-013-9977-z · 2.65 Impact Factor
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    ABSTRACT: Patients with primary immunodeficiency diseases (PIDD) may present with recurrent infections affecting different organs, organ-specific inflammation/autoimmunity, and also increased cancer risk, particularly hematopoietic malignancies. The diversity of PIDD and the wide age range over which these clinical occurrences become apparent often make the identification of patients difficult for physicians other than immunologists. The aim of this report is to develop a tool for educative programs targeted to specialists and applied by clinical immunologists. Considering the data from national surveys and clinical reports of experiences with specific PIDD patients, an evidence-based list of symptoms, signs, and corresponding laboratory tests were elaborated to help physicians other than immunologists look for PIDD. Tables including main clinical manifestations, restricted immunological evaluation, and possible related diagnosis were organized for general practitioners and 5 specialties. Tables include information on specific warning signs of PIDD for pulmonologists, gastroenterologists, dermatologists, hematologists, and infectious disease specialists. This report provides clinical immunologists with an instrument they can use to introduce specialists in other areas of medicine to the warning signs of PIDD and increase early diagnosis. Educational programs should be developed attending the needs of each specialty.
    Journal of Clinical Immunology 11/2013; 34(1). DOI:10.1007/s10875-013-9954-6 · 2.65 Impact Factor
  • Luke A Wall, Ricardo U Sorensen
    The Journal of pediatrics 10/2013; 163(6). DOI:10.1016/j.jpeds.2013.08.065 · 3.74 Impact Factor
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    Journal of Clinical Immunology 07/2013; 33(7). DOI:10.1007/s10875-013-9921-2 · 2.65 Impact Factor
  • Lily E Leiva, Hanh Monjure, Ricardo U Sorensen
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    ABSTRACT: OBJECTIVES: To investigate the immunological phenotypes detected in children with recurrent upper and lower respiratory infections that have normal total immunoglobulin concentrations. METHODS: A cohort of over 60 children with recurrent respiration infections was evaluated for specific antibody deficiencies (SAD) and for memory B-cell abnormalities. A control group of children without recurrent infections was also evaluated. Evaluation included a detailed history of immunizations with pneumococcal vaccines; determination of IgM, IgG, IgA, and IgE concentrations; measurement of anti-pneumococcal polysaccharide antibody levels by ELISA and expression of CD27, IgD, and IgM on peripheral CD19(+)B cells by flow cytometry to determine the proportions of naive, IgM-memory B cells, and class-switched memory B cells. RESULTS: Patients were classified as having a SAD to either pure polysaccharides (PPV-SAD) or to conjugate polysaccharides (PCV-SAD) based on the number of polysaccharides to which they developed an adequate antibody response. A normal response to only 2 or fewer of 7 PCV or PPV serotypes was considered as evidence of SAD. Forty-one patients without SAD and 26 with SAD were identified. IgM-memory B cells were low in 3 of 41 patients without SAD; in 3 of 5 PPV-SAD patients; and in 10 of 21 PCV-SAD patients. Class-switched memory B cells were low in 19 of 41 patients without SAD; in all 5 patients with PPV-SAD; and in 11 of 21PCV-SAD patients. CONCLUSIONS: Patients with recurrent infection with or without SAD may have low IgM- and/or class-switched memory B cells. Ongoing research aims to determine the prognostic implications of these differences in patients with SAD.
    Journal of Clinical Immunology 10/2012; DOI:10.1007/s10875-012-9814-9 · 2.65 Impact Factor
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    ABSTRACT: A major diagnostic intervention in the consideration of many patients suspected to have primary immunodeficiency diseases (PIDDs) is the application and interpretation of vaccination. Specifically, the antibody response to antigenic challenge with vaccines can provide substantive insight into the status of human immune function. There are numerous vaccines that are commonly used in healthy individuals, as well as others that are available for specialized applications. Both can potentially be used to facilitate consideration of PIDD. However, the application of vaccines and interpretation of antibody responses in this context are complex. These rely on consideration of numerous existing specific studies, interpolation of data from healthy populations, current diagnostic guidelines, and expert subspecialist practice. This document represents an attempt of a working group of the American Academy of Allergy, Asthma & Immunology to provide further guidance and synthesis in this use of vaccination for diagnostic purposes in consideration of PIDD, as well as to identify key areas for further research.
    The Journal of allergy and clinical immunology 09/2012; 130(3 Suppl):S1-24. DOI:10.1016/j.jaci.2012.07.002 · 11.25 Impact Factor
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    Amos Etzioni, Ricardo Sorensen
    04/2012; 69(2):149-150.
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    ABSTRACT: A large population of patients with recurring infections are undiagnosed or under diagnosed and Primary Immunodeficiency (PI) is more common than had been previously estimated. The results strongly indicate the measurable impact of Physician Education and Public Awareness in identifying patients with an underlying PI. The Jeffrey Modell Centers Network (JMCN) provides the infrastructure for referral, diagnosis and appropriate treatment. All disease classifications and identified defects increased significantly over the study period. Quality of Life for referred and diagnosed patients dramatically improved compared to undiagnosed patients. There is a substantial cost savings for diagnosed patients compared to undiagnosed, even if regular IgG is required. The SPIRIT(®) Software successfully identified patients with PI in a large database and at three pilot sites. The Software was successfully tested for specificity and sensitivity.
    Immunologic Research 09/2011; 51(1):61-70. DOI:10.1007/s12026-011-8241-y · 3.53 Impact Factor
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    ABSTRACT: Hypomorphic mutations in the nuclear factor-κB (NF-κB) essential modulator (NEMO) gene result in a variable syndrome of somatic and immunologic abnormalities. Clinically relevant genotype-phenotype associations are essential to understanding this complex disease. To study 2 unrelated boys with novel NEMO mutations altering codon 223 for similarity in phenotype in consideration of potential genotype-phenotype associations. Clinical and laboratory features, including cell counts, immunoglobulin quantity and quality, natural killer cell cytotoxicity, and Toll-like and tumor necrosis factor receptor signaling, were evaluated. Because both mutations affected NEMO codon 223 and were novel, consideration was given to new potential genotype-phenotype associations. Both patients were diagnosed as having hypohidrotic ectodermal dysplasia and had severe or recurrent infections. One had recurrent sinopulmonary infections and the other necrotizing soft tissue methicillin-resistant Staphylococcus aureus infection and Streptococcus anginosus subdural empyema with bacteremia. NEMO gene sequence demonstrated a 3-nucleotide deletion (c.667_669delGAG) in one patient and a substitution (667G>A) in the other. These findings predict either the deletion of NEMO glutamic acid 223 or it being replaced with lysine, respectively. Both patients had normal serum IgG levels but poor specific antibodies. Natural killer cell cytotoxicity and Toll-like and tumor necrosis factor receptor signaling were also impaired. Serious bacterial infection did not occur in both patients after immunoglobulin replacement therapy. Two different novel mutations affecting NEMO glutamic acid 223 resulted in clinically relevant similar phenotypes, providing further evidence to support genotype-phenotype correlations in this disease. They suggest NEMO residue 223 is required for ectodermal development and immunity and is apparently dispensable for quantitative IgG production but may be required for specific antibody production.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 07/2011; 107(1):50-6. DOI:10.1016/j.anai.2011.03.009 · 2.75 Impact Factor
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    ABSTRACT: The nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc) is metabolically incorporated into human tissues from certain mammalian-derived foods, and this occurs in the face of an anti-Neu5Gc "xeno-autoantibody" response. Given evidence that this process contributes to chronic inflammation in some diseases, it is important to understand when and how these antibodies are generated in humans. We show here that human anti-Neu5Gc antibodies appear during infancy and correlate with weaning and exposure to dietary Neu5Gc. However, dietary Neu5Gc alone cannot elicit anti-Neu5Gc antibodies in mice with a humanlike Neu5Gc deficiency. Other postnatally appearing anti-carbohydrate antibodies are likely induced by bacteria expressing these epitopes; however, no microbe is known to synthesize Neu5Gc. Here, we show that trace exogenous Neu5Gc can be incorporated into cell surface lipooligosaccharides (LOS) of nontypeable Haemophilus influenzae (NTHi), a human-specific commensal/pathogen. Indeed, infant anti-Neu5Gc antibodies appear coincident with antibodies against NTHi. Furthermore, NTHi that express Neu5Gc-containing LOS induce anti-Neu5Gc antibodies in Neu5Gc-deficient mice, without added adjuvant. Finally, Neu5Gc from baby food is taken up and expressed by NTHi. As the flora residing in the nasopharynx of infants can be in contact with ingested food, we propose a novel model for how NTHi and dietary Neu5Gc cooperate to generate anti-Neu5Gc antibodies in humans.
    Journal of Experimental Medicine 08/2010; 207(8):1637-46. DOI:10.1084/jem.20100575 · 13.91 Impact Factor
  • Journal of Allergy and Clinical Immunology 02/2010; 125(2):AB77. DOI:10.1016/j.jaci.2009.12.301 · 11.25 Impact Factor
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    ABSTRACT: Defects causing severe combined immunodeficiency (SCID) have been reported in pathways mediating antigen receptor rearrangement, antigen receptor and cytokine signaling, and purine metabolism. Recognizing that the actin regulator Coronin-1A is essential for development of a normal peripheral T cell compartment in mouse models, we identified absence of Coronin-1A in a girl with T−B+NK+ SCID who suffered recurrent infections including severe post-vaccination varicella at age 13 months. Murine Coronin-1A is essential for the release of T cells from the thymus, consistent with the paradoxically detectable thymus in our patient. Molecular analysis revealed a 2 bp deletion in the paternal CORO1A coding sequence paired with a 600 kb de novo deletion encompassing CORO1A on the maternal allele. This genomic region at 16p11.2 is subject to recurrent copy number variations associated with autism spectrum disorders, including attention deficit and hyperactivity, present in our patient. This case highlights the first link between actin cytoskeleton regulation and SCID.
    Clinical Immunology 04/2009; DOI:10.1016/j.clim.2008.11.002 · 3.99 Impact Factor
  • Luigi D Notarangelo, Ricardo Sorensen
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    ABSTRACT: The identification or the molecular bases of more than 130 primary immunodeficiency diseases has prompted the use of mutation analysis in the diagnostic approach to these patients. Here we discuss the importance of and the limitations associated with molecular diagnosis of these disorders and emphasize the need that mutation analysis be accompanied by appropriate evidence that the identified genetic defect has pathologic consequences on RNA/protein expression and function. U Allergy Clin Immunol 2008;122:1069-73.)
    The Journal of allergy and clinical immunology 12/2008; 122(6):1069-73. DOI:10.1016/j.jaci.2008.08.038 · 11.25 Impact Factor
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    ABSTRACT: Mice carrying the recessive locus for peripheral T cell deficiency (Ptcd) have a block in thymic egress, but the mechanism responsible is undefined. Here we found that Ptcd T cells had an intrinsic migration defect, impaired lymphoid tissue trafficking and irregularly shaped protrusions. Characterization of the Ptcd locus showed a point substitution of lysine for glutamic acid at position 26 in the actin regulator coronin 1A that enhanced its inhibition of the actin regulator Arp2/3 and resulted in its mislocalization from the leading edge of migrating T cells. The discovery of another coronin 1A mutant during an N-ethyl-N-nitrosourea-mutagenesis screen for T cell-lymphopenic mice prompted us to evaluate a T cell-deficient, B cell-sufficient and natural killer cell-sufficient patient with severe combined immunodeficiency, whom we found had mutations in both CORO1A alleles. Our findings establish a function for coronin 1A in T cell egress, identify a surface of coronin involved in Arp2/3 regulation and demonstrate that actin regulation is a biological process defective in human and mouse severe combined immunodeficiency.
    Nature Immunology 11/2008; 9(11):1307-15. DOI:10.1038/ni.1662 · 24.97 Impact Factor
  • Lily Leiva, Ricardo U. Sorensen
    Clinical Immunology 01/2008; 127. DOI:10.1016/j.clim.2008.03.196 · 3.99 Impact Factor
  • Kenneth Paris, Ricardo U Sorensen
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    ABSTRACT: This second article in the miniseries Practical Aspects of Ambulatory Diagnosis and Management of Immunodeficiency Disorders' extends the discussion on evaluation of individuals with suspected humoral immunodeficiency by reviewing the logistics and interpretation of the patient's ability to produce antibodies to polysaccharide antigens, specifically pneumococcal surface polysaccharides. The response to these polysaccharides is important in the evaluation of patients with documented immune abnormalities and those individuals who have normal total immunoglobulin levels. Although profound immune deficiencies, such as X-linked agammaglobulinemia and severe combined immunodeficiency, are always associated with a defect in specific antibody production, some immune disorders may have variable responses, whereas others with persistent IgG or IgG subclass deficiencies may have normal or clearly abnormal antipolysaccharide antibodies. Measurement of the response to pneumococcal polysaccharides is preferred because of the availability of a pure polysaccharide vaccine for antigen challenge and standardized techniques to measure specific antibody responses.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 12/2007; 99(5):462-4. DOI:10.1016/S1081-1206(10)60572-8 · 2.75 Impact Factor
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    ABSTRACT: We monitored Streptococcus pneumoniae serotypes causing invasive infections in patients admitted to one hospital in southern Chile during a 10-year period (1994 to 2004). All specimens isolated from patients with invasive S. pneumoniae infections were serotyped at the CDC in Atlanta, GA. A total of 508 isolates belonged to 58 serotypes. There were 95 infections in patients <2 years old, 33 infections in patients 2 to 4 years old, 61 infections in patients 5 to 14 years old, 66 infections in patients 15 to 44 years old, 134 infections in patients 45 to 64 years old, and 120 infections in patients >or=65 years old. The 10 serotypes isolated with the highest frequency in all groups were, in decreasing order, 1, 3, 14, 5, 19F, 6B, 7F, 12F, 23F, and 6A. The 10 most frequent isolates in children under 2 years of age were 1, 6B, 14, 19F, 5, 23F, 6A, 9V, and 7F. In patients >or=65 years old, the most common serotypes were 3, 7F, 1, 14, 19A, 23F, 19F, 35B, 4, and 5. Penicillin resistance was detected in 14 (2.7%) clinical specimens isolated since 1998, with 13 resistant strains identified since 2001. Vaccine coverage for the 7-valent conjugate vaccine was 42% for children <2 years of age. This study is important for the design of vaccines for this region and to evaluate public health measures to decrease pneumococcal infections.
    Clinical and Vaccine Immunology 06/2007; 14(6):660-4. DOI:10.1128/CVI.00379-06 · 2.37 Impact Factor
  • Ricardo Sorensen
    Journal of managed care pharmacy: JMCP 05/2007; 13(3):278-83. · 2.68 Impact Factor

Publication Stats

2k Citations
378.38 Total Impact Points

Institutions

  • 1991–2015
    • Louisiana State University Health Sciences Center New Orleans
      • Department of Pediatrics
      New Orleans, Louisiana, United States
  • 1998–2013
    • Children's Hospital New Orleans
      New Orleans, Louisiana, United States
    • LSU Medical Center
      • Department of Pediatrics
      New Orleans, Louisiana, United States
  • 2010
    • Louisiana State University Health Sciences Center Shreveport
      Shreveport, Louisiana, United States
  • 2007
    • Universidad de La Frontera
      Ciudad Temuco, Araucanía, Chile
  • 1993–2006
    • Louisiana State University
      Baton Rouge, Louisiana, United States
  • 2005
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 1999
    • University of Texas at Dallas
      Richardson, Texas, United States
  • 1989
    • Medical University of South Carolina
      • Department of Pediatrics
      Charleston, SC, United States
  • 1984–1988
    • Case Western Reserve University
      • • Institute of Pathology
      • • Rainbow Babies and Children's Hospital
      Cleveland, Ohio, United States
  • 1978–1988
    • Case Western Reserve University School of Medicine
      • Department of Pediatrics
      Cleveland, Ohio, United States