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    Scopus© Citations 3  2
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      10Scopus© Citations 10
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    Immune Dysregulation Mimicking Systemic Lupus Erythematosus in a Patient With Lysinuric Protein Intolerance: Case Report and Review of the Literature
    (2021)
    Josefina Longeri Contreras
    ;
    Mabel A. Ladino
    ;
    Katherine Aránguiz
    ;
    Gonzalo P. Mendez
    ;
    Zeynep Coban-Akdemir
    <jats:p>Lysinuric protein intolerance (LPI) is an inborn error of metabolism caused by defective transport of cationic amino acids in epithelial cells of intestines, kidneys and other tissues as well as non-epithelial cells including macrophages. LPI is caused by biallelic, pathogenic variants in <jats:italic>SLC7A7</jats:italic>. The clinical phenotype of LPI includes failure to thrive and multi-system disease including hematologic, neurologic, pulmonary and renal manifestations. Individual presentations are extremely variable, often leading to misdiagnosis or delayed diagnosis. Here we describe a patient that clinically presented with immune dysregulation in the setting of early-onset systemic lupus erythematosus (SLE), including renal involvement, in whom an LPI diagnosis was suspected post-mortem based on exome sequencing analysis. A review of the literature was performed to provide an overview of the clinical spectrum and immune mechanisms involved in this disease. The precise mechanism by which ineffective amino acid transport triggers systemic inflammatory features is not yet understood. However, LPI should be considered in the differential diagnosis of early-onset SLE, particularly in the absence of response to immunosuppressive therapy.</jats:p>
      5Scopus© Citations 18
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    Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children
    (2023)
    Danyel Lee
    ;
    Jérémie Le Pen
    ;
    Ahmad Yatim
    ;
    Beihua Dong
    ;
    Yann Aquino
    <jats:p> Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of <jats:italic>OAS1</jats:italic> , <jats:italic>OAS2</jats:italic> , or <jats:italic>RNASEL</jats:italic> in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)–sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the single-stranded RNA–degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L–deficient cells. Cytokine production in RNase L–deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS–RNase L deficiencies in these patients unleash the production of SARS-CoV-2–triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C. </jats:p>
      11Scopus© Citations 137
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    Three-Year Follow-up of 2-Dose Versus 3-Dose HPV Vaccine
    (2021)
    Jacob Bornstein
    ;
    Surita Roux
    ;
    Lone Kjeld Petersen
    ;
    Li-Min Huang
    ;
    Simon R. Dobson
    <jats:sec> <jats:title /> </jats:sec> <jats:sec> <jats:title>BACKGROUND AND OBJECTIVES:</jats:title> <jats:p>Human papillomavirus (HPV) antibody responses to the 9-valent human papillomavirus (9vHPV) vaccine among girls and boys (aged 9–14 years) receiving 2-dose regimens (months 0, 6 or 0, 12) were noninferior to a 3-dose regimen (months 0, 2, 6) in young women (aged 16–26 years) 4 weeks after last vaccination in an international, randomized, open-label trial (NCT01984697). We assessed response durability through month 36.</jats:p> </jats:sec> <jats:sec> <jats:title>METHODS:</jats:title> <jats:p>Girls received 2 (months 0 and 6 [0, 6]: n = 301; months 0 and 12 [0, 12]: n = 151) or 3 doses (months 0,2, and 6 [0, 2, 6]: n = 301); boys received 2 doses ([0, 6]: n = 301; [0, 12]: n = 150); and young women received 3 doses ([0, 2, 6]: n = 314) of 9vHPV vaccine. Anti-HPV geometric mean titers (GMTs) were assessed by competitive Luminex immunoassay (cLIA) and immunoglobulin G-Luminex immunoassay (IgG-LIA) through month 36.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS:</jats:title> <jats:p>Anti-HPV GMTs were highest 1 month after the last 9vHPV vaccine regimen dose, decreased sharply during the subsequent 12 months, and then decreased more slowly. GMTs 2 to 2.5 years after the last regimen dose in girls and boys given 2 doses were generally similar to or greater than GMTs in young women given 3 doses. Across HPV types, most boys and girls who received 2 doses (cLIA: 81%–100%; IgG-LIA: 91%–100%) and young women who received 3 doses (cLIA: 78%–98%; IgG-LIA: 91%–100%) remained seropositive 2 to 2.5 years after the last regimen dose.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS:</jats:title> <jats:p>Antibody responses persisted through 2 to 2.5 years after the last dose of a 2-dose 9vHPV vaccine regimen in girls and boys. In girls and boys, antibody responses generated by 2 doses administered 6 to 12 months apart may be sufficient to induce high-level protective efficacy through at least 2 years after the second dose.</jats:p> </jats:sec>
      13  1Scopus© Citations 26
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    Longitudinal assessment of SARS-CoV-2 IgG seroconversionamong front-line healthcare workers during the first wave of the Covid-19 pandemic at a tertiary-care hospital in Chile
    (2021)
    IRURETAGOYENA BRUCE, MIRENTXU INES  
    ;
    Macarena R. Vial
    ;
    Maria Spencer-Sandino
    ;
    Pablo Gaete
    ;
    Anne Peters
    <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Healthcare workers (HCWs) are at high risk of exposure to SARS-CoV-2. Cross-sectional studies have provided variable rates of seroprevalence in HCWs. Longitudinal assessments of the serological response to Covid-19 among HCWs are crucial to understanding the risk of infection and changes in antibody titers over time. We aimed to investigate seroprevalence and risk factors associated with seroconversion in a prospective cohort of HCWs during the peak of the first wave of the Covid-19 pandemic.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We conducted a longitudinal study among 446 front-line HCWsin a tertiary-care hospital in Chile from April to July 2020. IgG was determined monthly using two different ELISAs in serum samples of HCWs, during the three-month period. In each visit, demographic data, symptoms, risk factors, and exposure risks were also assessed.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>The overall seroprevalence at the end of the study period was 24% (95% CI20.2–28.3), with 43% of seropositive HCWs reporting no prior symptoms. Seroconversion rates significantly differed over the study period, from 2.1% to as high as 8.8% at the peak of the epidemic. There were no statistically significant differences observed between HCWs in direct clinical care of patients with Covid-19 and those working in low risk areas. Antibody titers appeared to wane over time.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>HCWs were severely affected with a high rate of seroconversion that appeared to mirror the local epidemiological situation. A significant amount of participants underwent an asymptomatic infection, highlighting the need for improved surveillance policies. Antibody titers appear to wane over time; further studies to understand this finding’s impact on the risk of reinfection are warranted.</jats:p> </jats:sec>
      1Scopus© Citations 21  2
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      1Scopus© Citations 1
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      4Scopus© Citations 29
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    Scrub Typhus in Continental Chile, 2016–2018
    (2019)
    WEITZEL, THOMAS  
    ;
    Constanza Martínez-Valdebenito
    ;
    Gerardo Acosta-Jamett
    ;
    Ju Jiang
    ;
    Allen L. Richards
      14Scopus© Citations 63