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1.
Arch Endocrinol Metab ; 68: e230115, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38456952

RESUMO

Thyroglobulin (Tg) levels are important to predict recurrence in differentiated thyroid cancer patients.However, false-positive results can hence the request of unnecessary tests and treatments. We reported two cases of interference in thyroglobulin measurement and the workup to investigate them. Both patients achieved an excellent response to therapy after total thyroidectomy and one patient had also received radioiodine treatment. During the follow-up, Tg levels increased and there was no evidence of recurrent disease in the imaging studies. The Tg levels by the Access platform were positive but the results by Elecsys platform and LC-MS/MS were undetectable, leading to the hypothesis of heterophile antibodies (HAbs) interference. The possibility of HAbs interference must be considered when the Tg levels do not fit in the clinical picture. The measurement of Tg by another immunoassay or by LC-MS/MS may be useful in these situations.


Assuntos
Tireoglobulina , Neoplasias da Glândula Tireoide , Humanos , Anticorpos Heterófilos , Radioisótopos do Iodo/uso terapêutico , Cromatografia Líquida , Espectrometria de Massas em Tandem , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia
2.
N Z Med J ; 137(1589): 12-19, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38301197

RESUMO

AIM: In patients with suspected venous thromboembolism, an elevated D-dimer level provides an important branch-point in the management pathway. This study compared two D-dimer assays, INNOVANCE® DDimer (Innovance) and STA®-Liatest® D-Di Plus (Liatest), to assess potential impact on clinical management. METHOD: Reflecting current practice in Waitemata, Auckland, we compared paired samples from 805 patients referred to hospital following a community D-dimer test. Samples were determined to be positive or negative using a 500µg/L fibrinogen equivalent units (FEU), and age-adjusted cut-offs. RESULTS: In the Innovance assay, 2% of samples had a result <500µg/L FEU. In contrast, by Liatest, 18% were below 500µg/L. This positive bias of Innovance was amplified with use of age-adjusted cut-offs; 23% of samples with an elevated Innovance result showed a normal result by Liatest. On average, the Innovance values were 22% higher than Liatest. Results suggestive of interference from heterophile antibodies were seen in 6% of sample-pairs. CONCLUSION: Innovance D-dimer test yielded higher values than Liatest and experienced interference from suspected heterophile antibodies. Discrepancies in nearly a quarter of patients may be leading to substantial under or over investigation, inefficient use of resources and clinical confusion.


Assuntos
Anticorpos Heterófilos , Laboratórios , Humanos , Estudos Retrospectivos , Nova Zelândia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hospitais
3.
Sci Rep ; 14(1): 718, 2024 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-38184699

RESUMO

Knowledge of factors associated with semen quality may help in investigations of the aetiology and pathophysiology. We investigated the correlation between biomarkers for testicular cell function (anti-müllerian hormone, AMH, Inhibin B, testosterone, free androgen-index (testosterone/sex-hormone binding globulin), insulin like peptide 3, INSL-3), alkaline phosphate (ALP), canine prostate-specific esterase (CPSE), and heterophilic antibodies with dog variables, semen quality, and fertility. Blood and semen were collected from 65 Bernese Mountain Dogs. We evaluated total sperm count, motility and morphological parameters. The semen quality ranged from poor to excellent, with an average total sperm count of 1.1 × 109 and 50% morphologically normal spermatozoa (MNS). Age and abnormal testicular consistency correlated with decreased motility and MNS. Higher ALP correlated with higher total sperm count. AMH could not be detected in seminal plasma. AMH in blood correlated with head defects and high AMH concentration correlated with a severe decline in several semen parameters. Testosterone was negatively and CPSE positively correlated with age. No correlations were found for INSL-3, inhibin B, or heterophilic antibodies. Our findings contribute to the understanding of factors associated with semen quality in dogs, particularly related to Sertoli cell function.


Assuntos
Líquidos Corporais , Hormônios Peptídicos , Masculino , Cães , Animais , Análise do Sêmen/veterinária , Sêmen , Hormônio Antimülleriano , Testosterona , Anticorpos Heterófilos , Esterases
4.
Curr Pediatr Rev ; 20(3): 305-322, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37526456

RESUMO

BACKGROUND: Infectious mononucleosis is common among adolescents and young adults. Although the majority of cases resolve spontaneously, life-threatening manifestations, and complications have been recognised. OBJECTIVE: The purpose of this article is to familiarize clinicians with the clinical manifestations, evaluation, diagnosis, and management of infectious mononucleosis. METHODS: A search was conducted in October 2022 in PubMed Clinical Queries using the key terms "infectious mononucleosis" OR "Epstein-Barr virus" OR "EBV". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the aforementioned search was used in the compilation of the present article. RESULTS: Infectious mononucleosis, caused by Epstein-Barr virus, most commonly affects adolescents and adults aged 15 to 24 years. Epstein-Barr virus is transmitted primarily in saliva. Infectious mononucleosis is characterized by a triad of fever, tonsillar pharyngitis, and lymphadenopathy. Fatigue may be profound but tends to resolve within three months. Periorbital and/or palpebral edema, typically bilateral, occurs in one-third of patients. Splenomegaly and hepatomegaly occur in approximately 50% and 10% of cases, respectively. A skin rash, which is usually widely scattered, erythematous, and maculopapular, occurs in approximately 10 to 45% of cases. Peripheral blood leukocytosis is observed in most patients; lymphocytes make up at least 50% of the white blood cell differential count. Atypical lymphocytes constitute more than 10% of the total lymphocyte count. The classic test for infectious mononucleosis is the demonstration of heterophile antibodies. The monospot test is the most widely used method to detect the serum heterophile antibodies of infectious mononucleosis. When confirmation of the diagnosis of infectious mononucleosis is required in patients with mononucleosis-like illness and a negative mono-spot test, serologic testing for antibodies to viral capsid antigens is recommended. Infectious mononucleosis is a risk factor for chronic fatigue syndrome. Spontaneous splenic rupture occurs in 0.1 to 0.5% of patients with infectious mononucleosis and is potentially life-threatening. Treatment is mainly supportive. Reduction of activity and bed rest as tolerated are recommended. Patients should be advised to avoid contact sports or strenuous exercise for 8 weeks or while splenomegaly is still present. Most patients have an uneventful recovery. CONCLUSION: Infectious mononucleosis is generally a benign and self-limited disease. Prompt diagnosis is essential to avoid unnecessary investigations and treatments and to minimize complications. Splenic rupture is the most feared complication. As avoiding exposure to EBV is almost impossible, the most effective way to prevent EBV infection and infectious mononucleosis is the development of an effective, safe, and affordable EBV vaccine that can confer life-long immunity.


Assuntos
Infecções por Vírus Epstein-Barr , Mononucleose Infecciosa , Ruptura Esplênica , Adolescente , Adulto Jovem , Humanos , Mononucleose Infecciosa/diagnóstico , Mononucleose Infecciosa/terapia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/terapia , Herpesvirus Humano 4 , Esplenomegalia/etiologia , Esplenomegalia/complicações , Anticorpos Heterófilos , Ruptura Esplênica/complicações
5.
Osteoporos Int ; 35(4): 737-740, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38151628

RESUMO

BACKGROUND: Parathyroid hormone (PTH) measurements can be falsely elevated due to the hormone binding to other molecules (macro-PTH) or immunoassay interference with heterophile, human anti-animal or other antibodies. This is rare but could lead to incorrect diagnosis, unnecessary investigations or avoidance of teriparatide treatment. We report a case of falsely high PTH levels due to assay interference and review the literature on cases of spuriously elevated PTH. CASE REPORT: An 87-year-old woman attending our bone health clinic with osteoporosis had persistently elevated PTH (383-784 pg/ml) using the Roche Cobas e801 immunoassay despite having normal serum calcium, phosphate, 25 hydroxyvitamin D (> 50 nmol/l) and eGFR (> 60 ml/min). To rule out falsely elevated PTH, a polyethylene glycol precipitation (PEG) test was performed which recovered less than 10% of the hormone resulting in a normal level. PTH was also tested on a different assay (Atellica Siemens) that identified a result of 27 pg/ml. The findings were consistent with immunoassay interference likely due to heterophile antibodies giving rise to a spuriously high PTH. DISCUSSION: The presence of unexpectedly high PTH levels should alert physicians to the possibility of false results due to assay interference or macro-PTH. This highlights the importance of clinically correlating results and of good communication with the testing laboratory. Here, we present the case of an 87-year-old woman with spuriously elevated PTH levels due to immunoassay interference likely mediated by heterophile antibodies. The presence of unexpectedly high PTH levels should prompt consideration of the possibility of false results due to assay interference or macro-PTH.


Assuntos
Anticorpos Heterófilos , Osteoporose , Feminino , Humanos , Idoso de 80 Anos ou mais , Hormônio Paratireóideo , Teriparatida/uso terapêutico , Imunoensaio/métodos , Osteoporose/complicações , Osteoporose/tratamento farmacológico
6.
Front Immunol ; 14: 1275658, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022676

RESUMO

Introduction: Microbial infections are associated with the occurrence of autoimmune diseases, but the mechanisms of microbial infection inducing autoimmune diseases are not fully understood. The existence of heterophilic antigens between microorganisms and human tissues may explain part of the pathogenesis of autoimmune diseases. Here, we investigate the distribution of heterophilic antigens and its relationship with autoimmune diseases. Methods: Monoclonal antibodies against a variety of microorganisms were prepared. The titer, subclass and reactivity of antibodies with microorganisms were identified, and heterophilic antibodies that cross-reacted with human tissues were screened by human tissue microarray. The reactivity of these heterophilic antibodies with different individuals and different species was further examined by immunohistochemistry. Results: In this study, 21 strains of heterophilic antibodies were screened. The results showed that these heterophilic antibodies were produced due to the existence of heterophilic antigens between microorganism and human body and the distribution of heterophilic antigens had individual, tissue and species differences. Conclusion: Our study showed that heterophilic antigens exist widely between microorganisms and human body, and the heterophilic antigens carried by microorganisms may break the immune tolerance of the body through carrier effect and initiate immune response, which may be one of the important mechanisms of infection inducing autoimmune diseases.


Assuntos
Antígenos Heterófilos , Doenças Autoimunes , Humanos , Anticorpos Monoclonais , Anticorpos Heterófilos , Imuno-Histoquímica
7.
Xenotransplantation ; 30(3): e12799, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36988069

RESUMO

Carbohydrate-specific antibodies are significant mediators of xenograft rejection. This study analyzed the carbohydrate specificity of antibodies in baboons before and after xenotransplantation of organs or injection of porcine red blood cells from hDAF transgenic pigs, using a glycan array with structurally defined glycans. Antibodies against hyaluronic acid disaccharide (HA2) showed the highest reactivity at baseline and rose after xenogeneic exposure. We also investigated in the serum of baboons that underwent xenotransplantation with either hDAF or hDAF/hMCP transgenic pig organs and Lewis rats after hamster-skin xenotransplantation the specificity of anti-HA antibodies on a glycan microarray representing HA oligosaccharides containing from two to 40 saccharides. Notably, the HA oligosaccharides ranging from 32 to 40 saccharides exhibited the highest antibody binding intensities at baseline in baboon and rat sera. After xenotransplantation, antibodies against HA38 and HA40 in baboons, and HA32, HA34, and HA36 in rats showed the highest titer increases. The changes of anti-HA IgM and IgG antibodies in rats after skin xenotransplantation was also confirmed by an ELISA specific for HA2, HA24, and HA85 antibodies. Thus, xenotransplantation is associated with increased antibodies against HA-oligosaccharides, which may represent a new target for intervention.


Assuntos
Anticorpos Heterófilos , Ácido Hialurônico , Animais , Suínos , Humanos , Ratos , Transplante Heterólogo , Ratos Endogâmicos Lew , Animais Geneticamente Modificados , Oligossacarídeos , Papio , Imunoglobulina G , Rejeição de Enxerto
8.
Clin Biochem ; 116: 24-30, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36889375

RESUMO

OBJECTIVES: The cardiac damage biomarkers cardiac troponin T (cTnT) and troponin I (cTnI) are used to identify patients with myocardial infarction (MI). To make the correct clinical decisions it is important to identify false positive results due to troponin assay interference. Often interferences are caused by high-molecular weight immunocomplexes called macrotroponin that may result in false troponin elevations because of delayed troponin clearance, or heterophilic antibodies that crosslink troponin assay antibodies and generate troponin-independent signals. DESIGN & METHODS: We describe and compare four methods for cTnI assay interference analysis using a protein G spin column method, gel filtration chromatography and two versions of a sucrose gradient ultracentrifugation for cTnI assay interference analysis on five patients with confirmed cTnI interference and one MI patient without cTnI interference from our troponin interference referral center. RESULTS: The protein G spin column method had a high between run variability but was still able to identify all five patients with cTnI interference. The sucrose gradient ultracentrifugation methods and the gel filtration method had simlar performancec and correctly identified the immunocomplexes that caused the cTnI interference. CONCLUSIONS: Our experience is that these methods are sufficient to safely confirm or exclude positive cTnI assay interference.


Assuntos
Infarto do Miocárdio , Troponina I , Humanos , Troponina T , Infarto do Miocárdio/diagnóstico , Anticorpos , Anticorpos Heterófilos , Biomarcadores
9.
Scand J Clin Lab Invest ; 83(2): 125-132, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36750978

RESUMO

Immune methods are measurement systems that can be affected by interference. The interfering substance may be endogenous immunoglobulins, antibodies, analyte-antibody complexes, and heterophile antibodies. In our study, we aimed to investigate the effect of macrovitamin B12 on high vitamin B12 levels measured using immune methods. Among the serum samples studied in our laboratory; serum from 145 individuals was determined as the patient group and serum from 50 individuals was determined as the control group. We investigated the effect of macroprotein on B12 measurement by using polyethylene glycol (PEG) precipitation, heterophile antibody blocking tube (HBT) and serial dilution methods. According to the recovery evaluation and the modified reference range evaluation after precipitation with PEG, the macrovitamin B12 percentage in the patient group was 58 (40%) and 65 (44.8%), respectively. There was no decrease in vitamin B12 values after the study with HBT. A lack of linearity was observed in 23 (18.7%) of 123 sera with serial dilution method. Macrovitamin B12 should be considered as a differential diagnosis of unexpectedly high vitamin B12 levels. According to the results of our study, we think that it would be appropriate to precipitate with PEG first when there is a suspicion of macrovitamin B12. In collaboration with clinical and laboratory, we recommend that the patient's clinical status and additional laboratory findings be examined, and the patient's sample should be evaluated and interpreted by a specialist in biochemistry by selecting the appropriate interference detection method.


Assuntos
Anticorpos Heterófilos , Vitamina B 12 , Humanos , Polietilenoglicóis/química , Anticorpos
10.
Am Fam Physician ; 107(1): 71-78, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36689975

RESUMO

Infectious mononucleosis is a viral syndrome characterized by fever, pharyngitis, and posterior cervical lymphadenopathy. It is usually caused by Epstein-Barr virus and most often affects adolescents and young adults 15 to 24 years of age. Primary transmission is through close personal contact with a person who is infected, particularly their saliva. Cost-effective, efficient initial laboratory testing for acute infectious mononucleosis includes complete blood count with differential (to assess for greater than 40% lymphocytes and greater than 10% atypical lymphocytes) and a rapid heterophile antibody test. The heterophile antibody test has a sensitivity of 87% and specificity of 91% but can have a false-negative result in children younger than five years and in adults during the first week of illness. The presence of elevated liver enzymes increases clinical suspicion for infectious mononucleosis in the setting of a negative heterophile antibody test result. Epstein-Barr viral capsid antigen-antibody testing is more sensitive and specific but more expensive and takes longer to process than the rapid heterophile antibody test. Treatment of infectious mononucleosis is supportive; routine use of antivirals and corticosteroids is not recommended. Current guidelines recommend that patients with infectious mononucleosis not participate in athletic activity for three weeks from onset of symptoms. Shared decision-making should be used to determine the timing of return to activity. Immunosuppressed populations are at higher risk of severe disease and significant morbidity. Epstein-Barr virus infection has been linked to nine types of cancer, including Hodgkin lymphoma, non-Hodgkin lymphoma, and nasopharyngeal carcinoma, and some autoimmune diseases.


Assuntos
Doenças Autoimunes , Infecções por Vírus Epstein-Barr , Mononucleose Infecciosa , Adolescente , Criança , Humanos , Anticorpos Heterófilos , Anticorpos Antivirais , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/terapia , Herpesvirus Humano 4 , Mononucleose Infecciosa/diagnóstico , Mononucleose Infecciosa/terapia
11.
J Clin Lab Anal ; 36(12): e24792, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36447406

RESUMO

BACKGROUND: We described a patient who exhibited a gradual increase in carbohydrate antigen 19-9 (CA19-9) concentrations for 4 years at three hospitals, with no associated clinical manifestations; however, we were unable to define the cause of this increase, forcing us to consider whether it was a false-positive result. METHODS: Given the potential for interference, this study used multiple system detection, gradient dilution, Polyethylene glycol (PEG) precipitation and heterophilic antibody blocking assay to evaluate the reliability of CA19-9 concentration increase. RESULTS: Analysis of the patient sample using multiple systems indicated that CA19-9 concentrations showed an obvious increase (154.0, and 889.2 IU/ml, respectively) using the Cobas E602 and Advia Centaur XP systems, and were within the reference ranges (<10 IU/ml) on other modules. PEG precipitation on the Cobas E602 and Advia Centaur XP systems reduced the CA19-9 concentration, as did heterophilic blocking tube (HBT-6, HBT-1) blockade. CONCLUSION: CA19-9 was incorrectly identified to increase due to the presence of heterophilic antibodies. We recommend that heterophilic antibodies should be evaluated in cases with elevated CA19-9 level but no associated clinical manifestations to prevent false positives.


Assuntos
Anticorpos Heterófilos , Antígeno CA-19-9 , Humanos , Reprodutibilidade dos Testes , Seguimentos , Carboidratos
12.
Ugeskr Laeger ; 184(38)2022 09 19.
Artigo em Dinamarquês | MEDLINE | ID: mdl-36178179

RESUMO

Heterophile antibodies can cause falsely elevated levels of prostate-specific antigen (PSA), which is illustrated in this case report with two patient cases. In the first case, the falsely elevated PSA resulted in thorough and unnecessary examinations with multiple transrectal biopsies causing psychological distress and a risk of infection. In the second case, a patient was diagnosed with prostate cancer, and falsely rising levels of PSA possibly resulted in prolonged treatment with medical castration. These cases underline the importance of suspecting interference, when clinical findings and PSA levels do not match.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Anticorpos Heterófilos , Biópsia/métodos , Humanos , Masculino , Próstata , Neoplasias da Próstata/terapia
13.
Clin Otolaryngol ; 47(6): 611-619, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35834363

RESUMO

INTRODUCTION: A large proportion of patients with infectious mononucleosis (IM) have abnormal liver function tests (LFT) at presentation. There is no guideline regarding the management and follow-up of these patients. Some patients also have abdominal ultrasound (US) due to deranged LFT, the need for this practice is unclear. The aim of this systematic review was to evaluate the evidence base on LFT assessment in IM, time to resolution of derangement, and the role of abdominal US. METHODS: A systematic search of PubMed, EMBASE and the Cochrane library was done. Two authors independently screened records for eligibility using pre-defined criteria. We included both adult and paediatric populations. Quality assessment of included studies was done. RESULTS: A total of 3924 patients were included from 32 studies, of which LFT values were reported on 2779 patients. A combination of typical clinical features, heterophile antibodies and Epstein-Barr virus-specific antibodies were used to ascertain diagnosis. The following proportion of patients had abnormal LFT: aspartate transaminase (57%); alanine transaminase (62%); alkaline phosphatase (65%); bilirubin (16%); gamma-glutamyltransferase (41%). Reported median (interquartile range) time to resolution of LFT was 8 (6-12) weeks (n = 438). Maximum time to resolution was >6 months. Clinical hepatomegaly and splenomegaly were found in 35% and 44% of patients, respectively. Enlarged liver and spleen on US were seen in 16 of 29 and 38 of 38 of patients, respectively. There were no reports of decompensated liver disease. CONCLUSION: Current evidence questions the need for routine assessment of LFT in immunocompetent patients presenting with IM; serial LFT assessments following initial abnormalities are not required in immunocompetent patients with subclinical derangement of LFT; routine US abdomen in IM to evaluate for derangement of LFT is not required.


Assuntos
Infecções por Vírus Epstein-Barr , Mononucleose Infecciosa , Hepatopatias , Adulto , Alanina Transaminase , Fosfatase Alcalina , Anticorpos Heterófilos , Aspartato Aminotransferases , Bilirrubina , Criança , Herpesvirus Humano 4 , Humanos , Mononucleose Infecciosa/diagnóstico por imagem , Hepatopatias/diagnóstico por imagem , Testes de Função Hepática , gama-Glutamiltransferase
14.
BMC Womens Health ; 22(1): 232, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710471

RESUMO

BACKGROUND: The optimal management of patients in reproductive endocrinology relies on the accuracy and validity of sex hormone assays. Endogenous or exogenous substances can compete with the analyte. This competition can result in interfering errors and falsely indicate elevated serum levels. Obvious interference in estradiol assays appears to occur rarely. Consequently, clinicians who are not familiar with the potential of interference could be misled. In addition to unnecessary investigations and interventions and severe mental stress, falsely elevated estradiol results can result in missed or delayed fertility opportunities. CASE: A 28-year-old female with pregnancy demand was diagnosed with polycystic ovary syndrome, Hashimoto's thyroiditis and subclinical hypothyroidism. She was found to have persistently elevated levels of serum estradiol in the early follicular phase (between 527 and 642 pg/mL). Screening workup was performed for nearly 11 months to find the causes. Serum tumor biomarkers were normal. Abdominal and pelvic computed tomography were negative for adrenal or adnexal masses. A left mesosalpinx cyst and benign pathological results were achieved by laparoscopic surgery. Hormonal substances and dietary supplements were absent, as determined by dietary records. Ultrasound confirmed follicles could grow slowly and eventually ovulate. Falsely elevated estradiol levels were suspected due to the discrepancy among high estradiol levels, follicle growth and normal gonadotropin levels. Immunological interference by heterophile antibody was finally verified by two competitive chemiluminescent immunoassay platforms (estradiol levels in the early follicle phase: 619 pg/mL, Siemens ADVIA CENTAUR and 60 pg/mL, Beckman, DxI 800). Successful clinical pregnancy was eventually achieved by combining induced ovulation, ultrasound monitoring and intercourse guidance. CONCLUSIONS: Analytical interference and laboratory error should be suspicious at first when the clinical characteristics contradict the laboratory results of serum hormones. Measuring serum estradiol with another immunoassay platform is an easy and non-time-consuming method to exclude the heterophile interfering.


Assuntos
Anticorpos Heterófilos , Hipotireoidismo , Adulto , Estradiol , Feminino , Fertilidade , Humanos , Imunoensaio/métodos , Gravidez
15.
Front Immunol ; 13: 830993, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251022

RESUMO

BACKGROUND: That Epstein-Barr virus (EBV) infection is associated with systemic lupus erythematosus (SLE) is established. The challenge is to explain mechanistic roles EBV has in SLE pathogenesis. Previous studies identify four examples of autoantibody cross-reactions between SLE autoantigens and Epstein-Barr nuclear antigen 1 (EBNA1). For two of these examples, the earliest detected autoantibody specifically cross-reacts with EBNA1; thereby, defined EBNA1 epitopes induce a robust autoantibody response in animals. These results suggest that the autoantibodies initiating the process leading to SLE may emerge from the anti-EBNA1 heteroimmune response. If this hypothesis is true, then anti-EBNA1 responses would be more frequent in EBV-infected SLE patients than in EBV-infected controls. We tested this prediction. METHODS: We evaluated published East Asian data by selecting those with a positive anti-viral capsid antigen (VCA) antibody immunoglobulin G (IgG) test and determining whether anti-EBNA1 was more common among the EBV-infected SLE cases than among matched EBV-infected controls with conditional logistic regression analysis. RESULTS: All the qualifying SLE patients (100%) in this dataset were EBV-infected compared to age- and sex-matched controls (92.2%) [odds ratio (OR) = 28.6, 95% CI 6.4-∞, p = 8.83 × 10-8], confirming the known close association of EBV infection with SLE. Furthermore, virtually all the SLE cases have both anti-VCA IgG and anti-EBNA1 IgG antibodies [124 of 125 (99.2%)], which are more frequently present than in age- and sex-matched EBV-infected controls [232 of 250 (93.2%)] (OR = 9.7, 95% CI 1.5-414, p = 0.0078) for an 89.7% SLE attributable risk from anti-EBNA1, which is in addition to the 100% SLE risk attributable to EBV infection in these data. CONCLUSIONS: The association of EBV infection with SLE is reconfirmed. The prediction that anti-EBNA1 is more frequent in these SLE cases than in EBV-infected controls is true, consistent with the hypothesis that anti-EBNA1 contributes to SLE. This second EBV-dependent risk factor is consistent with a molecular mimicry model for the generation of SLE, starting with EBV infection, progressing to anti-EBNA1 response; then molecular mimicry leads to anti-EBNA1 antibodies cross-reacting with an SLE autoantigen, causing autoantibody epitope spreading, and culminating in clinical SLE. These results support the anti-EBNA1 heteroimmune response being a foundation from which pathogenic SLE autoimmunity emerges.


Assuntos
Infecções por Vírus Epstein-Barr , Lúpus Eritematoso Sistêmico , Animais , Anticorpos Heterófilos , Anticorpos Antivirais , Autoanticorpos , Autoantígenos , Proteínas do Capsídeo , Epitopos , Antígenos Nucleares do Vírus Epstein-Barr , Herpesvirus Humano 4 , Humanos , Imunoglobulina G , Prevalência
17.
Front Immunol ; 12: 761250, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868003

RESUMO

Amino acid substitutions and deletions in the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can reduce the effectiveness of monoclonal antibodies (mAbs). In contrast, heterologous polyclonal antibodies raised against S protein, through the recognition of multiple target epitopes, have the potential to maintain neutralization capacities. XAV-19 is a swine glyco-humanized polyclonal neutralizing antibody raised against the receptor binding domain (RBD) of the Wuhan-Hu-1 Spike protein of SARS-CoV-2. XAV-19 target epitopes were found distributed all over the RBD and particularly cover the receptor binding motives (RBMs), in direct contact sites with the angiotensin converting enzyme-2 (ACE-2). Therefore, in Spike/ACE-2 interaction assays, XAV-19 showed potent neutralization capacities of the original Wuhan Spike and of the United Kingdom (Alpha/B.1.1.7) and South African (Beta/B.1.351) variants. These results were confirmed by cytopathogenic assays using Vero E6 and live virus variants including the Brazil (Gamma/P.1) and the Indian (Delta/B.1.617.2) variants. In a selective pressure study on Vero E6 cells conducted over 1 month, no mutation was associated with the addition of increasing doses of XAV-19. The potential to reduce viral load in lungs was confirmed in a human ACE-2 transduced mouse model. XAV-19 is currently evaluated in patients hospitalized for COVID-19-induced moderate pneumonia in phase 2a-2b (NCT04453384) where safety was already demonstrated and in an ongoing 2/3 trial (NCT04928430) to evaluate the efficacy and safety of XAV-19 in patients with moderate-to-severe COVID-19. Owing to its polyclonal nature and its glyco-humanization, XAV-19 may provide a novel safe and effective therapeutic tool to mitigate the severity of coronavirus disease 2019 (COVID-19) including the different variants of concern identified so far.


Assuntos
Anticorpos Heterófilos/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Heterófilos/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Variação Antigênica , Anticorpos Amplamente Neutralizantes/uso terapêutico , COVID-19/terapia , COVID-19/virologia , Modelos Animais de Doenças , Epitopos , Humanos , Imunização Passiva , Pulmão/efeitos dos fármacos , Pulmão/virologia , Camundongos , Domínios e Motivos de Interação entre Proteínas , Glicoproteína da Espícula de Coronavírus/genética , Suínos , Carga Viral/efeitos dos fármacos , Soroterapia para COVID-19
18.
Sci Transl Med ; 13(621): eabk1533, 2021 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-34818054

RESUMO

Broadly neutralizing antibodies (bNAbs) against HIV-1 develop after prolonged virus and antibody coevolution. Previous studies showed that sequential immunization with a V3-glycan patch germline-targeting HIV-1 envelope trimer (Env) followed by variant Envs can reproduce this process in mice carrying V3-glycan bNAb precursor B cells. However, eliciting bNAbs in animals with polyclonal antibody repertoires is more difficult. We used a V3-glycan immunogen multimerized on virus-like particles (VLPs), followed by boosting with increasingly native-like Env-VLPs, to elicit heterologous neutralizing antibodies in nonhuman primates (NHPs). Structures of antibody/Env complexes after prime and boost vaccinations demonstrated target epitope recognition with apparent maturation to accommodate glycans. However, we also observed increasing off-target antibodies with boosting. Eight vaccinated NHPs were subsequently challenged with simian-human immunodeficiency virus (SHIV), and seven of eight animals became infected. The single NHP that remained uninfected after viral challenge exhibited one of the lowest neutralization titers against the challenge virus. These results demonstrate that more potent heterologous neutralization resulting from sequential immunization is necessary for protection in this animal model. Thus, improved prime-boost regimens to increase bNAb potency and stimulate other immune protection mechanisms are essential for developing anti­HIV-1 vaccines.


Assuntos
Vacinas contra a AIDS , Anticorpos Anti-HIV , Infecções por HIV , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Vacinas contra a AIDS/imunologia , Animais , Anticorpos Heterófilos/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , HIV-1 , Imunização/métodos , Macaca , Polissacarídeos
20.
J Med Virol ; 93(11): 6404-6407, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34347299

RESUMO

Heterophile antibody assays have been used to aid the diagnosis of infectious mononucleosis caused by the Epstein-Barr virus. Seven commercially available assays currently widely utilized in clinical laboratories were compared in this study. Variable performance characteristics and assay times are observed, and these pieces of data may assist clinical laboratories in assay selection and result interpretation.


Assuntos
Anticorpos Heterófilos/sangue , Anticorpos Antivirais/sangue , Técnicas de Laboratório Clínico/normas , Infecções por Vírus Epstein-Barr/diagnóstico , Mononucleose Infecciosa/diagnóstico , Mononucleose Infecciosa/imunologia , Kit de Reagentes para Diagnóstico/normas , Adolescente , Anticorpos Heterófilos/imunologia , Criança , Técnicas de Laboratório Clínico/métodos , Infecções por Vírus Epstein-Barr/sangue , Humanos , Imunoglobulina M/sangue , Mononucleose Infecciosa/sangue , Adulto Jovem
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