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1.
Mult Scler ; 30(7): 888-892, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38406828

RESUMEN

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic offered an epidemiological opportunity to evaluate if isolation and masking affected John Cunningham (JC) virus transmission. OBJECTIVE: This study aimed to assess the proportion of natalizumab-treated patients who converted to a positive anti-JCV antibody serostatus before and during the pandemic. METHODS: Data from TYSABRI Outreach: Unified Commitment to Health (TOUCH) for 22,375 US patients treated with natalizumab with anti-JCV antibody records were assessed in epochs annually from 2017 to 2022. RESULTS: Pre-pandemic anti-JCV antibody serostatus change was observed for 7.4%-7.7%. During the first and second years of the pandemic, 7.3% and 7.2% of patients' serostatus changed, respectively. CONCLUSION: The proportion of patients with anti-JCV antibody serostatus change did not significantly differ during the first 2 years of the pandemic compared with prior years. In contrast to seasonal influenza, masking and social distancing had no discernable effect on JCV serostatus change.


Asunto(s)
Anticuerpos Antivirales , COVID-19 , Virus JC , Esclerosis Múltiple , Pandemias , Infecciones por Polyomavirus , Cuarentena , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Antivirales/análisis , Anticuerpos Antivirales/inmunología , COVID-19/epidemiología , COVID-19/prevención & control , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Virus JC/inmunología , Máscaras , Esclerosis Múltiple/epidemiología , Natalizumab/uso terapéutico , Pandemias/estadística & datos numéricos , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/prevención & control , Infecciones por Polyomavirus/transmisión , Cuarentena/estadística & datos numéricos , Serología , Factores de Tiempo , Estados Unidos/epidemiología
2.
Prenat Diagn ; 42(1): 87-96, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34893980

RESUMEN

BACKGROUND: The acronym 'TORCH' refers to well-recognised causes of perinatal infections: toxoplasmosis, rubella, cytomegalovirus (CMV) and herpes simplex virus (HSV). A TORCH serology panel is often used to test for maternal primary infection following detection of ultrasound abnormalities in pregnancy. AIM: This review aims to estimate the diagnostic yield of maternal TORCH serology in pregnancy following fetal ultrasound abnormalities. MATERIALS AND METHODS: Primary studies published since 2000 that assessed maternal TORCH serology for suspected fetal infection and included information on indications for testing, definition of positive TORCH serology results, and perinatal outcomes were included. RESULTS: Eight studies with a total of 2538 pregnancies were included. The main indications for testing were polyhydramnios, fetal growth restriction and hyperechogenic bowel. There were 26 confirmed cases of congenital CMV, of which 15 had multiple ultrasound abnormalities. There were no cases of congenital toxoplasmosis, rubella or HSV confirmed in any of the eight studies. CONCLUSIONS: The clinical utility of TORCH serology for non-specific ultrasound abnormalities such as isolated fetal growth restriction or isolated polyhydramnios is low. It is time to retire the TORCH acronym and the reflex ordering of 'TORCH' panels, as their continued use obscures, rather than illuminates, appropriate investigation for fetal ultrasound abnormalities.


Asunto(s)
Feto/anomalías , Infecciones/diagnóstico , Serología/normas , Adulto , Femenino , Feto/fisiopatología , Humanos , Infecciones/sangre , Pruebas Prenatales no Invasivas/métodos , Pruebas Prenatales no Invasivas/normas , Embarazo , Complicaciones Infecciosas del Embarazo/sangre , Complicaciones Infecciosas del Embarazo/diagnóstico , Resultado del Embarazo/epidemiología , Serología/métodos
3.
J Infect Dis ; 224(12 Suppl 2): S80-S85, 2021 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-34396401

RESUMEN

Chlamydia trachomatis (CT) causes pelvic inflammatory disease, which may result in tubal factor infertility (TFI) in women. Serologic assays may be used to determine the proportion of women with and without TFI who have had previous CT infection and to generate estimates of infertility attributable to chlamydia. Unfortunately, most existing CT serologic assays are challenged by low sensitivity and, sometimes, specificity for prior CT infection; however, they are currently the only available tests available to detect prior CT infection. Modeling methods such as finite mixture modeling may be a useful adjunct to quantitative serologic data to obtain better estimates of CT-related infertility. In this article, we review CT serological assays, including the use of antigens preferentially expressed during upper genital tract infection, and suggest future research directions. These methodologic improvements, coupled with creation of new biomarkers for previous CT infection, should improve our understanding of chlamydia's contribution to female infertility.


Asunto(s)
Anticuerpos Antibacterianos/inmunología , Infecciones por Chlamydia/complicaciones , Chlamydia trachomatis/inmunología , Infertilidad Femenina/etiología , Enfermedad Inflamatoria Pélvica/complicaciones , Anticuerpos Antibacterianos/sangre , Biomarcadores , Chlamydia trachomatis/aislamiento & purificación , Femenino , Humanos , Infertilidad Femenina/sangre , Infertilidad Femenina/microbiología , Enfermedad Inflamatoria Pélvica/microbiología , Serología
4.
Sex Transm Infect ; 97(7): 485-489, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33436504

RESUMEN

BACKGROUND: Considering the unknown prevalence of neurosyphilis in West China, and the confusing diagnosis of neurosyphilis, the role of CSF_CXCL13 and syphilis serology was studied to provide a more accurate reference for the clinical detection and diagnosis of neurosyphilis. METHODS: A retrospective data set I was used to investigate the prevalence of neurosyphilis, as well as the laboratory characteristics of 244 patients. Besides, to explore the diagnostic value of CSF_CXCL13 and syphilis serology for neurosyphilis, another 116 CSF_serum paired samples (data set II) were collected from 44 neurosyphilis and 72 non-neurosyphilis/syphilis patients. RESULTS: About 6.25% (156 out of 2494) syphilis was neurosyphilis. When Treponema pallidum infection occurs, syphilis serology (sero_TRUST ≥1:16 and sero_TPPA titre ≥1:10240) can be good predictors of neurosyphilis, as well as syphilis CSF serology (CSF_TPPA ≥1:320, CSF_TRUST and venereal disease research laboratory). The sensitivity of serology in neurosyphilis can be complemented by CSF_CXCL13, which could be the therapy monitor of neurosyphilis. CONCLUSION: Due to the lack of ideal biomarkers for neurosyphilis, the importance of syphilis serology cannot be ignored, and their combination with CSF_CXCL13 or other biomarkers should be further investigated.


Asunto(s)
Quimiocina CXCL13/líquido cefalorraquídeo , Neurosífilis/líquido cefalorraquídeo , Neurosífilis/diagnóstico , Adulto , Anciano , Biomarcadores , Estudios de Casos y Controles , Quimiocina CXCL13/sangre , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neurosífilis/sangre , Neurosífilis/inmunología , Estudios Retrospectivos , Sensibilidad y Especificidad , Serología/métodos , Serodiagnóstico de la Sífilis
5.
J Allergy Clin Immunol ; 145(4): 1031-1047, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32272980

RESUMEN

Autoimmune bullous skin diseases, such as pemphigus and pemphigoid, may enable clarification of the mechanisms of immune regulation in the skin. Pemphigus and pemphigoid are mediated by essentially IgG autoantibodies against structural proteins of the desmosomes at cell-cell junctions and hemidesmosomes at epidermal-dermal junctions, respectively, and are characterized by blisters and erosions in the skin and/or mucous membranes. Intensive investigation over the last 3 decades has identified their target antigens and developed serological diagnostic tools as well as mouse models to help us understand their pathophysiology. Based on these advances, several new therapeutic approaches have become available, and more effective and less toxic targeted approaches are under development.


Asunto(s)
Enfermedades Autoinmunes/inmunología , Penfigoide Ampolloso/inmunología , Pénfigo/inmunología , Enfermedades Cutáneas Vesiculoampollosas/inmunología , Piel/inmunología , Animales , Complejo Antígeno-Anticuerpo/metabolismo , Autoanticuerpos/metabolismo , Enfermedades Autoinmunes/diagnóstico , Desmosomas/inmunología , Modelos Animales de Enfermedad , Humanos , Ratones , Colágenos no Fibrilares/inmunología , Penfigoide Ampolloso/diagnóstico , Pénfigo/diagnóstico , Serología , Enfermedades Cutáneas Vesiculoampollosas/diagnóstico
6.
HIV Med ; 21(2): 128-134, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31702111

RESUMEN

OBJECTIVES: The aim of this study was to evaluate adherence to the recommendations of the Spanish guidelines for the initial assessment of patients with HIV infection in the multicentre Cohort of the Spanish HIV/AIDS Network (CoRIS) during the years 2004-2017. METHODS: We calculated the percentage of patients who had each of 11 clinical and analytical recommended examinations performed in their initial evaluation. We evaluated the factors associated with not performing each examination with multivariable logistic regression models. RESULTS: We included 13 612 patients in the study. In the initial assessment, CD4 count and viral load were determined in more than 98.0% of the patients. Serologies for hepatitis A, B and C and syphilis were determined in 55.8%, 66.4%, 89.8% and 81.7% of the patients, respectively. Total cholesterol and creatinine were determined in 78.7% and 78.9% of the patients, respectively. The lowest proportions of examinations were observed for blood pressure, smoking status and latent tuberculosis screening, which were performed in 43.2%, 50.6% and 53.9% of the patients, respectively. Injecting drug users and heterosexual patients (compared to men who have sex with men) and patients with a lower educational level had a higher risk of having an incomplete initial assessment for a substantial number of examinations. Latent tuberculosis screening was less likely in patients with CD4 counts < 200 cells/µL. CONCLUSIONS: The initial assessment of HIV-infected patients is suboptimal for the evaluation of cardiovascular risk, smoking status, screening of syphilis and viral hepatitis, and diagnosis of latent tuberculosis: adherence to the guidelines was low for these examinations.


Asunto(s)
Infecciones por VIH/inmunología , Hepatitis A/diagnóstico , Hepatitis B/diagnóstico , Hepatitis C/diagnóstico , Sífilis/diagnóstico , Adulto , Recuento de Linfocito CD4 , Femenino , Adhesión a Directriz , Infecciones por VIH/virología , Hepatitis A/inmunología , Hepatitis B/inmunología , Hepatitis C/inmunología , Humanos , Modelos Logísticos , Masculino , Guías de Práctica Clínica como Asunto , Serología , España , Sífilis/inmunología , Carga Viral
7.
Malar J ; 19(1): 159, 2020 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-32303235

RESUMEN

BACKGROUND: Profiling immune responses induced by either infection or vaccination can provide insight into identification of correlates of protection. Furthermore, profiling of serological responses can be used to identify biomarkers indicative of exposure to pathogens. Conducting such immune surveillance requires readout methods that are high-throughput, robust, and require small sample volumes. While the enzyme-linked immunosorbent assay (ELISA) is the classical readout method for assessing serological responses, the advent of multiplex assays has significantly increased the throughput and capacity for immunoprofiling. This report describes the development and assay performance (sensitivity, linearity of detection, requirement for multiple dilutions for each sample, intra- and inter-assay variability) of an electro-chemiluminescence (ECLIA)-based multiplex assay. METHODS: The current study describes the development of a multiplex ECLIA-based assay and characterizes the sensitivity, linear range, and inter- and intra-assay variability of the ECLIA platform and its agreement with the traditional ELISA. Special emphasis was placed on potential antigenic competition when testing closely related antigens in the multiplex format. RESULTS: Multiplexing of antigens in ECLIA provides significant practical benefits in terms of reducing sample volume requirements and experimental time. Beyond the practical advantages of multiplexing, the ECLIA provides superior assay performance when compared to the ELISA. Not only does ECLIA show good agreement with the ELISA assay, but the linear range of ECLIA is also sufficiently wide to permit single-dilution measurements of concentration without the need to do serial dilutions. The lack of antigenic competition allows the simultaneous testing of closely related antigens, such as plate antigens representing different alleles of the same protein, which can inform about cross-reactivities-or lack thereof-of serological responses. CONCLUSION: The advantages of the newly developed tool for assessing the antigen profiles of serological responses may ultimately lead to the identification of biomarkers associated with various disease stages and or protection against disease.


Asunto(s)
Fenómenos Fisiológicos Sanguíneos , Ensayo de Inmunoadsorción Enzimática/métodos , Mediciones Luminiscentes/métodos , Vacunas contra la Malaria/sangre , Malaria/prevención & control , Vacunación , Humanos , Sensibilidad y Especificidad , Serología
8.
J Immunol ; 201(11): 3211-3217, 2018 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-30373852

RESUMEN

Quantification of Abs toward a single epitope is critical to understanding immunobiological processes. In autoimmunity, the prognostic value of the serological profiles of patients draws much attention, but the detection of Abs toward a single epitope is not well controlled. Particularly, the rheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide Abs (ACPA) are specific to a two-atom change on arginyl residues and are considered a heterogeneous family of Abs. As a model, we studied ACPA to decipher how peptide features used as immunosorbent impact Ab detection. We synthesized 30 peptides encompassing immunodominant epitopes of citrullinated fibrin differing by their length and biotin location and tested them using ELISA with 120 sera from RA and non-RA rheumatic disease controls, generating over 3000 experimental measurements. We showed that minor molecular changes in peptide chemical structure had dramatic consequences. Even when peptides exhibited the same epitope, measured Ab titers were extremely variable, and patients' seropositivity was discordant in up to 50% of cases. The distance between epitope and biotin was the most critical parameter for efficient Ab detection irrespective of biotin position or peptide length. Finally, we identified a 15-mer peptide bearing a single citrullinated epitope detecting almost all ACPA-positive sera, thus revealing a high degree of homogeneity in RA autoimmune response. This integrative analysis deciphers the dramatic impact of the molecular design of peptide-based technologies for epitope-specific Ab quantification. It provides a model for assay development and highlights that the studies using such technologies can give a wrong perception of biological processes and therefore that medical use of data must be cautious.


Asunto(s)
Artritis Reumatoide/inmunología , Epítopos/química , Fibrina/química , Inmunoadsorbentes/química , Péptidos/química , Serología/métodos , Anticuerpos Antiproteína Citrulinada/metabolismo , Citrulinación , Errores Diagnósticos , Ensayo de Inmunoadsorción Enzimática , Epítopos/inmunología , Fibrina/inmunología , Humanos , Inmunidad Humoral , Péptidos/inmunología
9.
Am J Respir Crit Care Med ; 200(5): 535-550, 2019 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-31469325

RESUMEN

Background: Fungal infections are of increasing incidence and importance in immunocompromised and immunocompetent patients. Timely diagnosis relies on appropriate use of laboratory testing in susceptible patients.Methods: The relevant literature related to diagnosis of invasive pulmonary aspergillosis, invasive candidiasis, and the common endemic mycoses was systematically reviewed. Meta-analysis was performed when appropriate. Recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation approach.Results: This guideline includes specific recommendations on the use of galactomannan testing in serum and BAL and for the diagnosis of invasive pulmonary aspergillosis, the role of PCR in the diagnosis of invasive pulmonary aspergillosis, the role of ß-d-glucan assays in the diagnosis of invasive candidiasis, and the application of serology and antigen testing in the diagnosis of the endemic mycoses.Conclusions: Rapid, accurate diagnosis of fungal infections relies on appropriate application of laboratory testing, including antigen testing, serological testing, and PCR-based assays.


Asunto(s)
Candidiasis Invasiva , Cuidados Críticos , Aspergilosis Pulmonar Invasiva , Reacción en Cadena de la Polimerasa , Humanos , Candidiasis Invasiva/diagnóstico , Candidiasis Invasiva/inmunología , Cuidados Críticos/normas , Galactosa/análogos & derivados , Aspergilosis Pulmonar Invasiva/diagnóstico , Aspergilosis Pulmonar Invasiva/inmunología , Mananos , Reacción en Cadena de la Polimerasa/métodos , Serología/métodos , Sociedades Médicas , Estados Unidos
10.
Eye Contact Lens ; 46(3): 190-193, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31306215

RESUMEN

OBJECTIVES: The purpose of this study is to determine the utility of obtaining herpes simplex virus (HSV) serology for patients presenting with chronic corneal pathology of unknown etiology for which HSV is a diagnostic consideration. METHODS: A retrospective analysis was performed of all patients presenting to one cornea specialist (J.M.G.) between August 2011 and April 2018 with a chronic (>6 weeks) corneal condition for which HSV was suspected and serology was performed. Patient demographics, clinical presentation, treatment, final diagnosis, and follow-up duration were recorded. RESULTS: Fifty-four patients with a median age of 52 (range: 5-85) years were included in the study. Patients were classified by presenting clinical features as corneal ulcer (46.2%), stromal keratitis (24.1%), superficial keratitis (18.5%), or keratouveitis (11.1%). The seroprevalence of HSV-1 and HSV-2 antibodies were 42.6% and 18.5%, including 5 patients (9.3%) positive for both HSV-1 and HSV-2. Serology impacted management for all patients with negative titers (48.1%), defined as discontinuing antiviral medication, electing not to start antiviral medication, or continuing antiviral medication for a non-HSV etiology (e.g., varicella zoster keratitis). No patients with HSV serology were ultimately diagnosed with HSV keratitis. Median follow-up duration was 1.5 years (range 0.8-6.6 years). CONCLUSION: Although only useful when negative, our study confirms that serology may be useful for excluding HSV as a diagnostic consideration for patients presenting with chronic corneal pathology. The seroprevalence of HSV antibodies for our patient cohort was comparable with previous population-based studies.


Asunto(s)
Anticuerpos Antivirales/sangre , Herpesvirus Humano 1/inmunología , Queratitis Herpética/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Niño , Preescolar , Enfermedad Crónica , Femenino , Humanos , Inmunoensayo , Queratitis Herpética/sangre , Queratitis Herpética/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estudios Seroepidemiológicos , Serología/métodos
11.
J Investig Allergol Clin Immunol ; 29(3): 213-221, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30183656

RESUMEN

BACKGROUND AND OBJECTIVE: Alcohol consumption is associated with enhanced TH2 immune responses. Objective: To investigate the frequency of false-positive results in serological tests for allergy in alcoholic patients. METHODS: A total of 138 alcoholic patients consecutively admitted to hospital underwent a panel of allergy tests that included serum total IgE, a multiallergen IgE test (UniCAP Phadiatop), and skin prick tests to relevant aeroallergens in the area, which were considered the standard reference for atopy. In selected cases with positive specific IgE (sIgE) to cross-reactive carbohydrate determinants (CCDs) on ImmunoCAP, we determined sIgE to hymenoptera venom components (ADVIA Centaur) and a microarray of 103 allergen components (ISAC). RESULTS: Increased serum total IgE (>170 IU/mL) was observed in 59/110 (54%) of nonatopic (skin prick test-negative) patients. The result of the multiallergen IgE test was positive in 46 nonatopic patients (42%). This finding was closely associated with high serum concentrations of total IgE and sIgE to CCDs. The vast majority of patients with positive CCD-sIgE showed positivity to glycosylated plant and hymenoptera allergen components on ISAC and ADVIA Centaur. Only 1 out of 26 patients with positive sIgE to CCD and hymenoptera venom developed honeybee venom allergy after a median follow-up of 166 months. Correlations between measurements of sIgE to CCD markers on ImmunoCAP, ADVIA Centaur, and ISAC were imperfect. CONCLUSIONS: Serological tests for allergy should be interpreted with caution in alcoholic patients, who frequently have increased levels of total IgE and CCD-sIgE and subsequent positivity of sIgE to glycosylated allergen components, irrespective of the method used.


Asunto(s)
Alcoholismo/diagnóstico , Hipersensibilidad/diagnóstico , Inmunoglobulina E/sangre , Serología/métodos , Células Th2/inmunología , Adulto , Anciano , Alcoholismo/inmunología , Alérgenos/inmunología , Animales , Reacciones Cruzadas , Reacciones Falso Positivas , Femenino , Estudios de Seguimiento , Humanos , Himenópteros/inmunología , Hipersensibilidad/inmunología , Proteínas de Insectos/inmunología , Masculino , Persona de Mediana Edad , Pruebas Cutáneas , Ponzoñas/inmunología
12.
J Infect Chemother ; 25(1): 78-81, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30064948

RESUMEN

Healthcare workers (HCWs) are at an increased risk of being exposed to epidemic viral diseases (EVDs), such as measles, rubella, mumps, and varicella-zoster. Currently, in case of the absence of written records on previous immunizations, the Japanese Society for Infection Prevention and Control guidelines require HCWs to have antibody titers higher than laboratory thresholds, possibly leading to over-immunization. We report our vaccination strategy and the consequent incidences of EVDs at the Osaka University Hospital between 2000 and 2016. In 2001, we initiated an annual serology check of antibody titers against EVDs and immunization for newly employed HCWs. As an additional vaccination program, all HCWs with low antibody titers were vaccinated in 2005 and 2010. Antibody titers were determined by an enzyme immunoassay (EIA), with a positive range of >2.0 cut-off index. After implementing the vaccination strategy to keep the laboratory threshold, there were only sporadic cases of EVDs among HCWs. More than 99% of individuals who had positive titers in 2005 remained the positive antibody titers in 2010, indicating that a minimum interval of 5 years is enough to measure immunity. Unprotected workers can, even silently, transmit the contagious viruses to patients and coworkers, possibly resulting in a nosocomial outbreak. However, over-vaccination may yield adverse effects and financial burdens. Our observational data indicate that the laboratory cut-off index of >2.0 by EIA may provide a sufficient herd immunity to prevent EVDs among HCWs.


Asunto(s)
Anticuerpos Antivirales/inmunología , Infección Hospitalaria/prevención & control , Epidemias/prevención & control , Personal de Salud , Vacunación Masiva/métodos , Exposición Profesional/prevención & control , Virosis/prevención & control , Anticuerpos Antivirales/sangre , Infección Hospitalaria/epidemiología , Infección Hospitalaria/inmunología , Infección Hospitalaria/transmisión , Hospitales Universitarios , Humanos , Japón/epidemiología , Estudios Longitudinales , Estudios Retrospectivos , Serología , Factores de Tiempo , Virosis/epidemiología , Virosis/inmunología , Virosis/transmisión
13.
Sensors (Basel) ; 19(18)2019 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-31509969

RESUMEN

Food intolerance is delayed adverse food reactions which follow consumption of specific foods. The underlying mechanisms are not well understood, but food intolerance is often considered as a type 2 hypersensitivity reaction mediated by immunoglobulin G (IgG) antibody. To understand the causes of food intolerance, it is important to investigate sensitization patterns of food-specific IgGs (sIgG) in relation to dietary patterns and physical conditions. Conventional approaches to measure serological IgGs often require large volumes of serum, thus are not suitable for highly multiplexed assays. To overcome this impracticality, we developed a highly sensitive method to screen the sIgGs and other antibody isotypes against 66 antigens with minimal amount of serums. We prepared a microarray by immobilizing food antigens on activated glass slides. Human sera and their dietary information were obtained from 30 subjects. Aliquots (200 nl) of sera were analyzed against 66 food antigens in parallel. sIgG levels were determined and analyzed in relation to subjects' dietary patterns. The levels of antibody isotypes were also examined to understand the relationship between allergy and food intolerance. The developed microarray showed exceptional performances in antibody screening and demonstrated the potential to be used as an automated assay system.


Asunto(s)
Antígenos/análisis , Alimentos , Isotipos de Inmunoglobulinas/sangre , Análisis por Micromatrices/métodos , Microtecnología/métodos , Serología , Adulto , Dieta , Femenino , Humanos , Persona de Mediana Edad
14.
Immunology ; 153(3): 279-289, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29139548

RESUMEN

Antibodies are highly functional glycoproteins capable of providing immune protection through multiple mechanisms, including direct pathogen neutralization and the engagement of their Fc portions with surrounding effector immune cells that induce anti-pathogenic responses. Small modifications to multiple antibody biophysical features induced by vaccines can significantly alter functional immune outcomes, though it is difficult to predict which combinations confer protective immunity. In order to give insight into the highly complex and dynamic processes that drive an effective humoral immune response, here we discuss recent applications of 'Systems Serology', a new approach that uses data-driven (also called 'machine learning') computational analysis and high-throughput experimental data to infer networks of important antibody features associated with protective humoral immunity and/or Fc functional activity. This approach offers the ability to understand humoral immunity beyond single correlates of protection, assessing the relative importance of multiple biophysical modifications to antibody features with multivariate computational approaches. Systems Serology has the exciting potential to help identify novel correlates of protection from infection and may generate a more comprehensive understanding of the mechanisms behind protection, including key relationships between specific Fc functions and antibody biophysical features (e.g. antigen recognition, isotype, subclass and/or glycosylation events). Reviewed here are some of the experimental and computational technologies available for Systems Serology research and evidence that the application has broad relevance to multiple different infectious diseases including viruses, bacteria, fungi and parasites.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Inmunidad Humoral/inmunología , Humanos , Serología/métodos , Vacunas/inmunología
16.
J Neuroinflammation ; 15(1): 166, 2018 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-29807534

RESUMEN

BACKGROUND: A wealth of evidence implicates both central and peripheral immune changes as contributing to the pathogenesis of Parkinson's disease (PD). It is critical to better understand this aspect of PD given that it is a tractable target for disease-modifying therapy. Age-related changes are known to occur in the immune system (immunosenescence) and might be of particular relevance in PD given that its prevalence rises with increasing age. We therefore sought to investigate this with respect to T cell replicative senescence, a key immune component of human ageing. METHODS: Peripheral blood mononuclear cells were extracted from blood samples from 41 patients with mild PD (Hoehn and Yahr stages 1-2, mean (SD) disease duration 4.3 (1.2) years) and 41 age- and gender-matched controls. Immunophenotyping was performed with flow cytometry using markers of T lymphocyte activation and senescence (CD3, CD4, CD8, HLA-DR, CD38, CD28, CCR7, CD45RA, CD57, CD31). Cytomegalovirus (CMV) serology was measured given its proposed relevance in driving T cell senescence. RESULTS: Markers of replicative senescence in the CD8+ population were strikingly reduced in PD cases versus controls (reduced CD57 expression (p = 0.005), reduced percentage of 'late differentiated' CD57loCD28hi cells (p = 0.007) and 'TEMRA' cells (p = 0.042)), whilst expression of activation markers (CD28) was increased (p = 0.005). This was not driven by differences in CMV seropositivity. No significant changes were observed in the CD4 population. CONCLUSIONS: This study demonstrates for the first time that the peripheral immune profile in PD is distinctly atypical for an older population, with a lack of the CD8+ T cell replicative senescence which characterises normal ageing. This suggests that 'abnormal' immune ageing may contribute to the development of PD, and markers of T cell senescence warrant further investigation as potential biomarkers in this condition.


Asunto(s)
Envejecimiento/patología , Inmunosenescencia , Enfermedad de Parkinson/patología , Linfocitos T/metabolismo , Anciano , Antígenos CD/metabolismo , Estudios de Casos y Controles , Senescencia Celular , Citomegalovirus/inmunología , Femenino , Citometría de Flujo , Humanos , Inmunoglobulina G , Inmunofenotipificación , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/sangre , Serología
17.
Mult Scler ; 24(5): 563-573, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28847222

RESUMEN

BACKGROUND: Anti-John Cunningham virus (JCV) serology has been studied with varying results concerning longitudinal changes. OBJECTIVES AND METHODS: Results from 17 published natalizumab-treated multiple sclerosis (MS) patient cohorts were analyzed with common parameters and subsequently verified in two large independent cohorts with 722 and 499 patients from Germany and the United States. RESULTS: Published studies and the verification showed (1) a mean of 10.80% sero-negative patients presented with sero-status change to positivity per year; (2) patients, who sero-convert to index values <0.9, convert from near the threshold and have a high probability of reverting with time; (3) patients, who convert to index values >0.9, start with low index values; (4) while JCV sero-positive patients with low index values sometimes revert to sero-negativity, patients with high index values almost never revert; and (5) the conversion rate of natalizumab-treated patients is three to four times higher than the biological conversion by age. CONCLUSION: JCV sero-conversion was comparable using standardized parameters and indicates influence of natalizumab on JCV immune control. Converters to low index values are probably consistently infected with JCV with varying low levels of activity, in line with their low risk to develop progressive multifocal leukoencephalopathy (PML). Patients with high index values rarely revert back to sero-negativity.


Asunto(s)
Anticuerpos Antivirales/sangre , Biomarcadores/sangre , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/uso terapéutico , Virus JC/inmunología , Leucoencefalopatía Multifocal Progresiva/etiología , Esclerosis Múltiple/sangre , Esclerosis Múltiple/tratamiento farmacológico , Natalizumab/efectos adversos , Natalizumab/uso terapéutico , Serología , Adolescente , Adulto , Factores de Edad , Estudios de Cohortes , Estudios Transversales , Femenino , Alemania , Humanos , Factores Inmunológicos/inmunología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Natalizumab/inmunología , Riesgo , Factores Sexuales , Utah , Adulto Joven
18.
Virol J ; 15(1): 165, 2018 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-30359262

RESUMEN

BACKGROUND: Limited data are available on the incidence of variations in nucleotide sequences of long terminal repeat (LTR) regions of Bovine Leukemia Virus (BLV). Consequently, the possible impact of SNPs on BLV LTR function are poorly elucidated. Thus, a detailed and representative study of full-length LTR sequences obtained from sixty-four BLV isolates from different geographical regions of Poland, Moldova, Croatia, Ukraine and Russia were analyzed for their genetic variability. METHODS: Overlap extension PCR, sequencing and Bayesian phylogenetic reconstruction of LTR sequences were performed. These analyses were followed by detailed sequence comparison, estimation of genetic heterogeneity and identification of transcription factor binding site (TFBS) modifications. RESULTS: Phylogenetic analysis of curated LTR sequences and those available in the GenBank database reflected the acknowledged env gene classification of BLV into 10 genotypes, and further clustered analysed sequences into three genotypes - G4, G7 and G8. Additional molecular studies revealed the presence of 97 point mutations distributed at 89 positions throughout all 64 LTR sequences. The highest rate of variability was noted in U3 and U5 subregions. However, the variability in regulatory sequences (VR) was assessed as lower than the variability within non-regulatory sequences (VNR) for both, U3 and U5 subregions. In contrast, VR value for R subregion, as well as for the total LTR, was higher than the VNR suggesting the existence of positive selection. Twelve unique SNPs for these LTR sequences localized in regulatory and non-regulatory elements were identified. The presence of different types of substitutions lead to the abrogation of present or to the creation of additional TFBS. CONCLUSION: This study represents the largest study of LTR genetic variability of BLV field isolates from Eastern part of Europe. Phylogenetic analysis of LTRs supports the clustering BLV variants based on their geographic origin. The SNP screening showed variations modifying LTR regulatory sequences, as well as altering TFBS. These features warrant further exploration as they could be related to proviral load and distinctive regulation of BLV transcription and replication.


Asunto(s)
Leucosis Bovina Enzoótica/virología , Virus de la Leucemia Bovina/genética , Polimorfismo de Nucleótido Simple , ARN Viral/genética , Secuencias Repetidas Terminales/genética , Animales , Bovinos , Croacia , Leucosis Bovina Enzoótica/sangre , Leucosis Bovina Enzoótica/diagnóstico , Leucocitos Mononucleares/virología , Moldavia , Filogenia , Polonia , ARN Viral/sangre , Elementos Reguladores de la Transcripción , Federación de Rusia , Análisis de Secuencia de ADN , Serología , Ucrania
19.
J Infect Chemother ; 24(10): 789-794, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30007865

RESUMEN

BACKGROUND: Inappropriate inflammatory response in children with M. pneumoniae infection might be associated with disease severity. The role of Granulocyte macrophage colony stimulating factor (GM-CSF) in hospitalized children with Mycoplasma pneumoniae pneumonia (MPP) has not been fully discussed. METHODS: Clinical and laboratory data of a total 40 children with MPP were collected. GM-CSF and myeloperoxidase (MPO) were detected by ELISAs. Meanwhile, normal human bronchial epithelium was infected by M. pneumoniae and neutrophils were stimulated by GM-CSF to explore GM-CSF and MPO release in supernatant, respectively. RESULTS: Compared to control group, a significant increased percentage of neutrophils and decreased percentage of macrophages in bronchoalveolar lavage fluid of children with MPP was observed (P < 0.05). Children with MPP had significantly higher levels of GM-CSF (P = 0.0047) and MPO (P = 0.0002) in BALF compared to the controls. Level of GM-CSF in BALF was associated with duration of fever (r = 0.42, P = 0.007) and strongly correlated with level of MPO (r = 0.075, P = 0.0005). Levels of GM-CSF and MPO significantly decreased (both P < 0.05) after treatment. In vitro, M. pneumoniae induced GM-CSF expression in a time-dependent manner during a 72-h period (P < 0.05) and MPO secretion significantly increased by recombinant human GM-CSF stimulation at 24h (P < 0.05). CONCLUSION: GM-CSF could be induced by M. pneumoniae infection in vivo and vitro. Childen with high level GM-CSF had longer duration of fever. GM-CSF probably plays a vital role in neutrophil inflammation in M. pneumoniae infection.


Asunto(s)
Líquido del Lavado Bronquioalveolar/química , Factor Estimulante de Colonias de Granulocitos y Macrófagos/análisis , Mycoplasma pneumoniae/inmunología , Neumonía por Mycoplasma/inmunología , Niño , Femenino , Fiebre/inmunología , Hospitales Universitarios , Humanos , Macrófagos Alveolares , Masculino , Neutrófilos/inmunología , Peroxidasa/análisis , Proteínas Recombinantes/metabolismo , Serología
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