Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 54.723
Filtrar
1.
Eur Rev Med Pharmacol Sci ; 28(4): 1314-1326, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38436165

RESUMO

OBJECTIVE: Pulmonary arterial hypertension (PAH) represents an important vascular complication of mixed connective tissue disease (MCTD) and systemic sclerosis (SSc). Microvascular involvement in these diseases can be investigated by means of nailfold capillaroscopy (NFC). Microvascular involvement detected in the nailfold bed is the mirror of the microvascular damage occurring in the entire body, further indicating the involvement of the target organs. The aim of this study was to evaluate the microvascular involvement in MCTD patients with or without PAH, compared to that found in SSc patients with or without PAH. PATIENTS AND METHODS: This cross-sectional study was performed in the Department of Internal Medicine and Department of Rheumatology, Timișoara, Romania, during the time period between January 2017 and December 2022, on a group of 26 patients with MCTD and 26 SSc patients. Antinuclear antibodies, anti-U1-RNP, anti-Scl 70, anti-centromere, anti-cardiolipin antibodies (aCL) (IgM, IgG), anti-ß2-glycoprotein I (aß2GPI) (IgM, IgG) antibodies, and lupus anticoagulant (LAC) were determined in both the groups. PAH was evaluated through cardiac ultrasonography, determining the sPAP (systolic pulmonary artery pressure). Nailfold capillaroscopy was performed using a USB Digital Microscope and 2.0-megapixel digital camera recording capillaries density, giant capillaries, enlarged capillaries, capillaries hemorrhages, avascular areas, ramified/bushy capillaries scores. Data were recorded and presented as mean ± standard deviation. Statistical analyses were performed using the Student's t-test, ANOVA test, and Pearson's correlation. Differences were considered statistically significant if p-value < 0.05. RESULTS: Among the MCTD patients, PAH was identified in 12 patients (46.15%), while among the SSc patients PAH was identified in 14 patients (53.84%). Development of PAH in MCTD patients was associated with lower capillaries density (p-value < 0.00001), higher scores of giant capillaries, ramified/bushy capillaries, and capillary hemorrhages (p-value < 0.00001, for each of them). Anti-U1-RNP, aCL, aß2GPI antibodies and LAC were also found to be involved in PAH-associated MCTD development. Unlike MCTD patients, SSc patients with PAH presented with lower capillaries density and ramified/bushy capillaries scores (p-value < 0.05). CONCLUSIONS: The MCTD patients who presented significant NFC abnormalities (especially active and late scleroderma-like capillaroscopic pattern) are prone to PAH development. Capillary density reduction is the most important factor associated with the occurrence of PAH. Differences in NFC findings (especially capillary density and ramified/bushy capillaries) were detected among patients with MCTD and SSc having PAH.


Assuntos
Síndrome Antifosfolipídica , Hipertensão Pulmonar , Doença Mista do Tecido Conjuntivo , Hipertensão Arterial Pulmonar , Escleroderma Sistêmico , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Angioscopia Microscópica , Doença Mista do Tecido Conjuntivo/complicações , Estudos Transversais , Escleroderma Sistêmico/complicações , Imunoglobulina G , Hemorragia , Imunoglobulina M
2.
PeerJ ; 12: e17012, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464758

RESUMO

Purpose: The purpose of this study was to investigate the relationship between serum immunoglobulin M (IgM) and the severity of coronary artery disease in Chinese patients who underwent coronary angiography. Methods: A total of 2,045 patients who underwent coronary angiography (CAG) from March 2017 to March 2020 at Beijing Hospital were included in this study. Serum IgM concentration and biochemical indicators were measured before coronary angiography (CAG). The triquartile IgM levels at baseline in the population were analysed. Spearman rank correlation was used to analyse the association between IgM and traditional risk factors for coronary artery disease (CAD). CAD patients were divided into subgroups by affected area, number of affected vessels, and Gensini score to analyse the relationship between IgM and CAD severity. Multivariable logistic regression analysis was used to evaluate the association between IgM and CAD severity. Results: Serum IgM levels were significantly lower in the CAD group (63.5 mg/dL) than in the non-coronary artery disease (NCAD) group (72.3 mg/dL) (P < 0.001). Serum IgM levels were significantly associated with sex. Serum IgM levels were positively correlated with traditional CAD risk factors such as TG, TC and LDL-C (P < 0.05), and negatively associated with the number of obstructed vessels, the number of affected areas, and Gensini scores. After adjusting for age, sex, smoking status, hypertension, dyslipidaemia, diabetes, stroke, and statin use history, a high IgM level was independently negatively associated with the severity of CAD expressed by the Gensini score. Conclusion: We determined that serum IgM was independently negatively associated with the severity of CAD diagnosed by angiography in Chinese adults.


Assuntos
Doença da Artéria Coronariana , Hipertensão , Adulto , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Angiografia Coronária , Fatores de Risco , Imunoglobulina M
3.
Autoimmunity ; 57(1): 2323563, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38465789

RESUMO

Unlike Fc receptors for switched immunoglobulin (Ig) isotypes, Fc receptor for IgM (FcµR) is selectively expressed by lymphocytes. The ablation of the FcµR gene in mice impairs B cell tolerance as evidenced by concomitant production of autoantibodies of IgM and IgG isotypes. In this essay, we reiterate the autoimmune phenotypes observed in mutant mice, ie IgM homeostasis, dysregulated humoral immune responses including autoantibodies, and Mott cell formation. We also propose the potential phenotypes in individuals with FCMR deficiency and the model for FcµR-mediated regulation of self-reactive B cells.


Assuntos
Autoimunidade , Receptores Fc , Camundongos , Animais , Receptores Fc/genética , Autoanticorpos , Imunoglobulina M
4.
Medicine (Baltimore) ; 103(10): e37332, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457548

RESUMO

RATIONALE: Hemorrhagic fever with renal syndrome (HFRS) is a common infectious disease in China. As a complication of post-Hantavirus infection, Guillain-Barre syndrome (GBS) was rarely previously reported. Here, we described a case of acute inflammatory demyelinative polyradiculoneuropathy secondary to Hantavirus infection in spring of 2023. We also made a summary of the clinical features from previous reported cases. PATIENT CONCERNS: A young male patient complained a fever with headache, who was subsequently diagnosed with HFRS with positive serum Hantavirus antibody IgM. Two weeks later, he presented sustained back pain, obvious numbness located in 4 extremities, chest and abdomen, facial dyskinesia and 4 extremities muscle weakness. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: He was rapidly diagnosed with GBS by typical cerebrospinal fluid change and the electromyography examination presentation, which was verified associated with hantavirus infection. He was treated with intravenous immunoglobulin infusion followed by rehabilitation treatment. He got a complete recovery within 4 months after disease onset. LESSONS: GBS was an uncommon manifestation of Hantavirus infection. GBS should be considered when acute limb weakness happens in cases with HFRS. A multidisciplinary team could make a rapid diagnosis and optimal treatment when nervous system disorders occurred.


Assuntos
Síndrome de Guillain-Barré , Infecções por Hantavirus , Febre Hemorrágica com Síndrome Renal , Humanos , Masculino , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/terapia , Febre Hemorrágica com Síndrome Renal/complicações , Febre Hemorrágica com Síndrome Renal/diagnóstico , Infecções por Hantavirus/complicações , Infecções por Hantavirus/diagnóstico , Infecções por Hantavirus/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Debilidade Muscular/tratamento farmacológico , Imunoglobulina M , Anticorpos Antivirais
5.
Handb Clin Neurol ; 200: 239-273, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38494281

RESUMO

Peripheral neuropathy is a common referral for patients to the neurologic clinics. Paraneoplastic neuropathies account for a small but high morbidity and mortality subgroup. Symptoms include weakness, sensory loss, sweating irregularity, blood pressure instability, severe constipation, and neuropathic pain. Neuropathy is the first presenting symptom of malignancy among many patients. The molecular and cellular oncogenic immune targets reside within cell bodies, axons, cytoplasms, or surface membranes of neural tissues. A more favorable immune treatment outcome occurs in those where the targets reside on the cell surface. Patients with antibodies binding cell surface antigens commonly have neural hyperexcitability with pain, cramps, fasciculations, and hyperhidrotic attacks (CASPR2, LGI1, and others). The antigenic targets are also commonly expressed in the central nervous system, with presenting symptoms being myelopathy, encephalopathy, and seizures with neuropathy, often masked. Pain and autonomic components typically relate to small nerve fiber involvement (nociceptive, adrenergic, enteric, and sudomotor), sometimes without nerve fiber loss but rather hyperexcitability. The specific antibodies discovered help direct cancer investigations. Among the primary axonal paraneoplastic neuropathies, pathognomonic clinical features do not exist, and testing for multiple antibodies simultaneously provides the best sensitivity in testing (AGNA1-SOX1; amphiphysin; ANNA-1-HU; ANNA-3-DACH1; CASPR2; CRMP5; LGI1; PCA2-MAP1B, and others). Performing confirmatory antibody testing using adjunct methods improves specificity. Antibody-mediated demyelinating paraneoplastic neuropathies are limited to MAG-IgM (IgM-MGUS, Waldenström's, and myeloma), with the others associated with cytokine elevations (VEGF, IL6) caused by osteosclerotic myeloma, plasmacytoma (POEMS), and rarely angiofollicular lymphoma (Castleman's). Paraneoplastic disorders have clinical overlap with other idiopathic antibody disorders, including IgG4 demyelinating nodopathies (NF155 and Contactin-1). This review summarizes the paraneoplastic neuropathies, including those with peripheral nerve hyperexcitability.


Assuntos
Síndrome de Isaacs , Mieloma Múltiplo , Polineuropatia Paraneoplásica , Doenças do Sistema Nervoso Periférico , Humanos , Polineuropatia Paraneoplásica/diagnóstico , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/terapia , Autoanticorpos , Nervos Periféricos , Imunoglobulina M , Dor
6.
Proc Natl Acad Sci U S A ; 121(11): e2318657121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38446855

RESUMO

Viral mimicry of host cell structures has been postulated to curtail the B cell receptor (BCR) repertoire against persisting viruses through tolerance mechanisms. This concept awaits, however, experimental testing in a setting of natural virus-host relationship. We engineered mouse models expressing a monoclonal BCR specific for the envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV), a naturally persisting mouse pathogen. When the heavy chain of the LCMV-neutralizing antibody KL25 was paired with its unmutated ancestor light chain, most B cells underwent receptor editing, a behavior reminiscent of autoreactive clones. In contrast, monoclonal B cells expressing the same heavy chain in conjunction with the hypermutated KL25 light chain did not undergo receptor editing but exhibited low levels of surface IgM, suggesting that light chain hypermutation had lessened KL25 autoreactivity. Upon viral challenge, these IgMlow cells were not anergic but up-regulated IgM, participated in germinal center reactions, produced antiviral antibodies, and underwent immunoglobulin class switch as well as further affinity maturation. These studies on a persisting virus in its natural host species suggest that central tolerance mechanisms prune the protective antiviral B cell repertoire.


Assuntos
Linfócitos B , Tolerância Central , Animais , Camundongos , Anticorpos Antivirais , Vírus da Coriomeningite Linfocítica , Antivirais , Imunoglobulina M
7.
Front Immunol ; 15: 1325387, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469296

RESUMO

Introduction: This study aimed to delineate longitudinal antibody responses to the Pfizer-BioNTech BNT162b2 COVID-19 vaccine within the Ugandan subset of the Sub-Saharan African (SSA) demographic, filling a significant gap in global datasets. Methods: We enrolled 48 participants and collected 320 specimens over 12 months after the primary vaccination dose. A validated enzyme-linked immunosorbent assay (ELISA) was used to quantify SARS-CoV-2-specific IgG, IgM, and IgA antibody concentrations (ng/ml) and optical densities (ODs). Statistical analyses included box plots, diverging bar graphs, and the Wilcoxon test with Bonferroni correction. Results: We noted a robust S-IgG response within 14 days of the primary vaccine dose, which was consistent with global data. There was no significant surge in S-IgG levels after the booster dose, contrasting trends in other global populations. The S-IgM response was transient and predominantly below established thresholds for this population, which reflects its typical early emergence and rapid decline. S-IgA levels rose after the initial dose then decreased after six months, aligning with the temporal patterns of mucosal immunity. Eleven breakthrough infections were noted, and all were asymptomatic, regardless of the participants' initial S-IgG serostatus, which suggests a protective effect from vaccination. Discussion: The Pfizer-BioNTech BNT162b2 COVID-19 vaccine elicited strong S-IgG responses in the SSA demographic. The antibody dynamics distinctly differed from global data highlighting the significance of region-specific research and the necessity for customised vaccination strategies.


Assuntos
Imunoglobulina G , Vacinas , Humanos , Vacina BNT162 , Formação de Anticorpos , Vacinas contra COVID-19 , Uganda , Vacinação , Anticorpos Antivirais , Políticas , Imunoglobulina M
8.
PLoS Negl Trop Dis ; 18(3): e0012030, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38452046

RESUMO

BACKGROUND: Brucellosis, a widely spread zoonotic disease, poses significant diagnostic challenges due to its non-specific symptoms and underreporting. Timely and accurate diagnosis is crucial for effective patient management and public health control. However, a comprehensive comparative review of available diagnostic tests is lacking. METHODOLOGY/PRINCIPAL FINDINGS: This systematic review addressed the following question: 'What is the accuracy of the available tests to confirm human brucellosis?' Two independent reviewers examined articles published up to January 2023. The review included original studies reporting symptomatic patients with brucellosis suspicion, through any index test, with sensitivity and/or specificity as outcomes. As exclusion criteria were considered: sample size smaller than 10 patients, studies focusing on complicated brucellosis, and those lacking essential information about index or comparator tests. Sensitivity and specificity were assessed, with consideration for the index test, and 'culture' and 'culture and standard tube agglutination test (SAT)' were used as reference standards. Bias assessment and certainty of evidence were carried out using the QUADAS-2 and GRADE tools, respectively. A total of 38 studies reporting diagnostic test performance for human brucellosis were included. However, the evidence available is limited, and significant variability was observed among studies. Regarding the reference test, culture and/or SAT are deemed more appropriate than culture alone. Rose Bengal, IgG/IgM ELISA, and PCR exhibited equally high performances, indicating superior overall diagnostic accuracy, with very low certainty of the evidence. CONCLUSIONS/SIGNIFICANCE: This systematic review underscores the potential of the Rose Bengal test, IgG/IgM ELISA, and PCR as promising diagnostic tools for brucellosis. However, the successful implementation and recommendations for their use should consider the local context and available resources. The findings highlight the pressing need for standardization, improved reporting, and ongoing advancements in test development to enhance the accuracy and accessibility of brucellosis diagnosis.


Assuntos
Brucelose , Rosa Bengala , Humanos , Brucelose/diagnóstico , Sensibilidade e Especificidade , Imunoglobulina G/análise , Imunoglobulina M
9.
PLoS One ; 19(3): e0298730, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38483868

RESUMO

INTRODUCTION: A lateral flow rapid diagnostic test (RDT) enables detection of measles specific immunoglobulin M (IgM) antibody in serum, capillary blood, and oral fluid with accuracy consistent with enzyme immunoassay (EIA). The objectives of the study were: 1) to assess measles RDT inter-reader agreement between two clinic staff; 2) to assess the sensitivity and specificity of the measles RDT relative to standard surveillance testing in a low transmission setting; 3) to evaluate the knowledge, attitudes, and practices of staff in clinics using the RDT; and 4) to assess the impact of RDT testing on the measles public health response in Malaysia. MATERIALS AND METHODS: The clinic-based prospective evaluation included all suspected measles cases captured by routine measles surveillance at 34 purposely selected clinics in 15 health districts in Malaysia between September 2019 and June 2020, following day-long regional trainings on RDT use. Following informed consent, four specimens were collected from each suspected case, including those routinely collected for standard surveillance [serum for EIA and throat swabs for quantitative reverse transcriptase polymerase chain reaction (RT-qPCR)] together with capillary blood and oral fluid tested with RDTs during the study. RDT impact was evaluated by comparing the rapidity of measles public health response between the pre-RDT implementation (December 2018 to August 2019) and RDT implementation periods (September 2019 to June 2020). To assess knowledge, attitudes, and practices of RDT use, staff involved in the public health management of measles at the selected sites were surveyed. RESULTS: Among the 436 suspect cases, agreement of direct visual readings of measles RDT devices between two health clinic staff was 99% for capillary blood (k = 0.94) and 97% for oral fluid (k = 0.90) specimens. Of the total, 45 (10%) were positive by measles IgM EIA (n = 44, including five also positive by RT-qPCR) or RT-qPCR only (n = 1), and 38 were positive by RDT (using either capillary blood or oral fluid). Using measles IgM EIA or RT-qPCR as reference, RDT sensitivity using capillary blood was 43% (95% CI: 30%-58%) and specificity was 98% (95% CI: 96%-99%); using oral fluid, sensitivity (26%, 95% CI: 15%-40%) and specificity (97%, 95% CI: 94%-98%) were lower. Nine months after training, RDT knowledge was high among staff involved with the public health management of measles (average quiz score of 80%) and was highest among those who received formal training (88%), followed by those trained during supervisory visits (83%). During the RDT implementation period, the number of days from case confirmation until initiation of public response decreased by about 5 days. CONCLUSION: The measles IgM RDT shows >95% inter-reader agreement, high retention of RDT knowledge, and a more rapid public health response. However, despite ≥95% RDT specificity using capillary blood or oral fluid, RDT sensitivity was <45%. Higher-powered studies using highly specific IgM assays and systematic RT-qPCR for case confirmation are needed to establish the role of RDT in measles elimination settings.


Assuntos
Sarampo , Testes de Diagnóstico Rápido , Humanos , Imunoglobulina M , Malásia/epidemiologia , Sarampo/diagnóstico , Sarampo/epidemiologia , Técnicas Imunoenzimáticas , Sensibilidade e Especificidade
10.
Sci Rep ; 14(1): 6151, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486038

RESUMO

Regular monitoring of blood glucose levels is essential for the management of diabetes and the development of appropriate treatment protocols. The conventional blood glucose (BG) testing have an intrusive technique to prick the finger and it can be uncomfortable when it is a regular practice. Intrusive procedures, such as fingerstick testing has negatively influencing patient adherence. Diabetic patients now have an exceptional improvement in their quality of life with the development of cutting-edge sensors and healthcare technologies. intensive care unit (ICU) and pregnant women also have facing challenges including hyperglycemia and hypoglycemia. The worldwide diabetic rate has incited to develop a wearable and accurate non-invasive blood glucose monitoring system. This research developed an Internet of Things (IoT) - enabled wearable blood glucose monitoring (iGM) system to transform diabetes care and enhance the quality of life. The TTGOT-ESP32 IoT platform with a red and near-infrared (R-NIR) spectral range for blood glucose measurement has integrated into this wearable device. The primary objective of this gadget is to provide optimal comfort for the patients while delivering a smooth monitoring experience. The iGM gadget is 98.82 % accuracy when used after 10 hours of fasting and 98.04 % accuracy after 2 hours of breakfast. The primary objective points of the research were continuous monitoring, decreased risk of infection, and improved quality of life. This research contributes to the evolving field of IoT-based healthcare solutions by streaming real-time glucose values on AWS IoT Core to empower individuals with diabetes to manage their conditions effectively. The iGM Framework has a promising future with the potential to transform diabetes management and healthcare delivery.


Assuntos
Diabetes Mellitus , Internet das Coisas , Humanos , Feminino , Gravidez , Glicemia , Automonitorização da Glicemia/métodos , Qualidade de Vida , Diabetes Mellitus/terapia , Imunoglobulina M
11.
Sci Rep ; 14(1): 6748, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514826

RESUMO

The data regarding primary FSGS (pFSGS) from different parts of the world differ. While the prevalence of pFSGS has been increasing in Western countries like the USA, it follows an inconsistent trend in Europe and Asia and a decreasing trend in Far Eastern countries such as China in the last two decades. There are undetermined factors to explain those national and geographic discrepancies. Herein, we aimed to reveal the current prevalence with clinical and histopathological characteristics of pFSGS in Turkish adults. This study includes the biopsy-proven pFSGS patients data recorded between 2009 and 2019, obtained from the national multicenter primary glomerulonephritis registry system of the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database. 850 of the 3875 primer glomerulonephritis patients(21.9%) have pFSGS. The mean age is 40.5 ± 14.2 and 435 (51.2%) of patients are male. Nephrotic syndrome is the most common biopsy indication (59.2%). 32.6% of patients have hematuria, 15.2% have leukocyturia and 7.8% have both. Serum creatinine, albumin, and proteinuria are 1.0 mg/dL (IQR = 0.7-1.4) mg/dl, 3.4 ± 0.9 g/dl, 3400 mg/day(IQR, 1774-5740), respectively. Females have lower mean arterial pressure (- 2.2 mmHg), higher eGFR (+ 10.0 mL/min/1.73 m2), and BMI (+ 1.6 kg/m2) than males. Thickened basal membrane(76.6%) and mesangial proliferation (53.5%) on light microscopy are the major findings after segmental sclerosis. IgM (32.7%) and C3 (32.9%) depositions are the most common findings on immunofluorescence microscopy. IgM positivity is related to lower eGFR, serum albumin, and higher proteinuria. The prevalence of pFSGS is stable although slightly increasing in Turkish adults. The characteristics of the patients are similar to those seen in Western countries.


Assuntos
Glomerulonefrite , Glomerulosclerose Segmentar e Focal , Adulto , Feminino , Humanos , Masculino , Glomerulosclerose Segmentar e Focal/epidemiologia , Glomerulosclerose Segmentar e Focal/patologia , Proteinúria , Biópsia , Albumina Sérica , Imunoglobulina M , Estudos Retrospectivos
12.
J Exp Med ; 221(5)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38512136

RESUMO

Diffuse large B cell lymphoma of activated B cell type (ABC-DLBCL), a major cell-of-origin DLBCL subtype, is characterized by chronic active B cell receptor (BCR) signaling and NF-κB activation, which can be explained by activating mutations of the BCR signaling cascade in a minority of cases. We demonstrate that autonomous BCR signaling, akin to its essential pathogenetic role in chronic lymphocytic leukemia (CLL), can explain chronic active BCR signaling in ABC-DLBCL. 13 of 18 tested DLBCL-derived BCR, including 12 cases selected for expression of IgM, induced spontaneous calcium flux and increased phosphorylation of the BCR signaling cascade in murine triple knockout pre-B cells without antigenic stimulation or external BCR crosslinking. Autonomous BCR signaling was associated with IgM isotype, dependent on somatic BCR mutations and individual HCDR3 sequences, and largely restricted to non-GCB DLBCL. Autonomous BCR signaling represents a novel immunological oncogenic driver mechanism in DLBCL originating from individual BCR sequences and adds a new dimension to currently proposed genetics- and transcriptomics-based DLBCL classifications.


Assuntos
Leucemia Linfocítica Crônica de Células B , Linfoma Difuso de Grandes Células B , Animais , Camundongos , Linfócitos B , Linfoma Difuso de Grandes Células B/genética , Receptores de Antígenos de Linfócitos B , Imunoglobulina M
13.
Methods Mol Biol ; 2789: 185-192, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38507004

RESUMO

Polyethylene glycol, or PEG, is common in consumer products, over-the-counter medications, food, and pharmaceutical products. Concerns about PEG immunogenicity and the subsequent negative impact of pre-existing and product-induced antibodies often shadow the benefits of using PEG in nanotechnology-based products. Such anti-PEG antibodies contribute to the accelerated blood clearance of PEGylated nanomedicines and result in premature drug release and antibody-mediated toxicities. Recent data demonstrated that using PEG in COVID-19 lipid nanoparticle-mRNA vaccines is associated with an induction of anti-PEG antibodies in healthy individuals, further contributing to the development or boosting of pre-existing antibodies and increasing the risks of antibody-mediated toxicities to other products containing PEG. Therefore, monitoring the levels of pre-existing and product-induced anti-PEG antibodies provides mechanistic insights for pharmacology, toxicology, and immunological studies of PEGylated drug products.


Assuntos
Lipossomos , Polietilenoglicóis , Humanos , Polietilenoglicóis/farmacologia , Anticorpos , Imunoglobulina M
14.
Front Immunol ; 15: 1314507, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487524

RESUMO

Background: Rheumatoid factors (RFs) are autoantibodies that target the Fc region of IgG, and are found in patients with rheumatic diseases as well as in the healthy population. Many studies suggest that an immune trigger may (transiently) elicit RF responses. However, discrepancies between different studies make it difficult to determine if and to which degree RF reactivity can be triggered by vaccination or infection. Objective: We quantitatively explored longitudinal RF responses after SARS-CoV-2 vaccination and infection in a well-defined, large cohort using a dual ELISA method that differentiates between true RF reactivity and background IgM reactivity. In addition, we reviewed existing literature on RF responses after vaccination and infection. Methods: 151 healthy participants and 30 RA patients were included to measure IgM-RF reactivity before and after SARS-CoV-2 vaccinations by ELISA. Additionally, IgM-RF responses after a SARS-CoV-2 breakthrough infection were studied in 51 healthy participants. Results: Published prevalence studies in subjects after infection report up to 85% IgM-RF seropositivity. However, seroconversion studies (both infection and vaccination) report much lower incidences of 2-33%, with a trend of lower percentages observed in larger studies. In the current study, SARS-CoV-2 vaccination triggered low-level IgM-RF responses in 5.5% (8/151) of cases, of which 1.5% (2/151) with a level above 10 AU/mL. Breakthrough infection was accompanied by development of an IgM-RF response in 2% (1/51) of cases. Conclusion: Our study indicates that de novo RF induction following vaccination or infection is an uncommon event, which does not lead to RF epitope spreading.


Assuntos
Artrite Reumatoide , COVID-19 , Humanos , Fator Reumatoide , Infecções Irruptivas , Vacinas contra COVID-19 , SARS-CoV-2 , COVID-19/prevenção & controle , Autoanticorpos , Imunoglobulina M , Vacinação
15.
Proc Natl Acad Sci U S A ; 121(13): e2313672121, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38502693

RESUMO

Memory B cells (MBCs) play a critical role in protection against homologous and variant pathogen challenge by either differentiating to plasma cells (PCs) or to germinal center (GC) B cells. The human MBC compartment contains both switched IgG+ and unswitched IgM+ MBCs; however, whether these MBC subpopulations are equivalent in their response to B cell receptor cross-linking and their resulting fates is incompletely understood. Here, we show that IgG+ and IgM+ MBCs can be distinguished based on their response to κ-specific monoclonal antibodies of differing affinities. IgG+ MBCs responded only to high-affinity anti-κ and differentiated almost exclusively toward PC fates. In contrast, IgM+ MBCs were eliminated by apoptosis by high-affinity anti-κ but responded to low-affinity anti-κ by differentiating toward GC B cell fates. These results suggest that IgG+ and IgM+ MBCs may play distinct yet complementary roles in response to pathogen challenge ensuring the immediate production of high-affinity antibodies to homologous and closely related challenges and the generation of variant-specific MBCs through GC reactions.


Assuntos
Switching de Imunoglobulina , Células B de Memória , Humanos , Linfócitos B , Antígenos , Imunoglobulina G , Imunoglobulina M , Memória Imunológica
16.
Front Immunol ; 15: 1338937, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38449861

RESUMO

Introduction: The mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), produced by Fusarium fungi, are frequently found in the cereal-rich diet of pigs and can modulate the immune system. Some enzymes or bacteria present in the digestive tract can de-epoxydize DON to deepoxy-deoxynivalenol (DOM-1) and biotransform ZEN into hydrolyzed ZEN (HZEN). The effects of these metabolites on immune cells, particularly with respect to the vaccine responses, are poorly documented. The aim of this study was to address the impact of DON and ZEN and their respective derivatives, on proliferation, and antibody production of porcine B cells in vitro. Methods: Peripheral blood mononuclear cells (PBMCs), isolated from healthy pigs, were stimulated with the Toll-like receptor (TLR) 7/8-agonist Resiquimod (R848) or the TLR/1/2-agonist Pam3Cys-SKKKK in combination with DON [0.1-1.6 µM] or DOM-1 [1.6 µM and 16 µM] and ZEN [2.5-40 µM] or HZEN [40 µM]. Results: A strong decrease in B-cell proliferation was observed at DON concentrations equal to or exceeding 0.8 µM and at ZEN concentrations equal to or exceeding 20 µM. Treatment with 1.6 µM DON or 40 µM ZEN led to almost a complete loss of live CD79α+ B cells. Moreover, CD21 expression of proliferating IgG+ and IgM+ B-cell subsets was decreased at DON concentrations equal to and exceeding 0.4 µM and at ZEN concentrations equal to or exceeding 10 µM. ELISpot assays revealed a decrease of IgG-secreting B cells at concentrations of and exceeding 0.4 µM and at ZEN concentrations equal to and exceeding 10 µM. ELISA assays showed a decrease of IgM, IgG, and IgA secretion at concentrations equal to or exceeding 0.4 µM DON. ZEN reduced IgM secretion at 20-40 µM (both R848 and Pam3Cys-SKKKK), IgG secretion at 40 µM (both R848 and Pam3Cys-SKKKK) and IgA secretion at 20-40 µM. Discussion: Our in vitro experiments show that while DON and ZEN impair immunoglobulin production and B-cell proliferation, this effect is abrogated by HZEN and DOM-1.


Assuntos
Tricotecenos , Zearalenona , Animais , Suínos , Formação de Anticorpos , Leucócitos Mononucleares , Proliferação de Células , Adjuvantes Imunológicos , ELISPOT , Imunoglobulina A , Imunoglobulina G , Imunoglobulina M
17.
Cytokine ; 177: 156564, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38432065

RESUMO

OBJECTIVE: The SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), leads to severe pathogenicity and high mortality among different communities around the world. Therefore, it is important to understand the mechanisms of virus pathogenesis and the immune system's response to prevent the further spread of this virus. This study was aimed to evaluate the relationship between the serum level of interleukin 6 and positive IgG and IgM antibody levels in patients with COVID-19 to investigate inflammation and disease progression. METHODS & MATERIALS: In this study, 10 ml of EDTA blood samples were taken from 414 COVID-19 patients. Then, the plasma was separated and the levels of IgM and IgG antibodies and interleukin 6 cytokine were evaluated by ELISA and chemiluminescence methods, respectively. All data were analyzed by SPSS 22 and GraphPad prism 9 software at the significance level of P < 0.05. RESULTS: The results of this study showed that there was no significant difference in the expression of IgM and IgG antibodies between men and women. Also, a significant increase in the mean expression of IL-6 was observed only in the high concentration range (100-〉1000 pg/ml) in men compared to women (P < 0.001). In addition, in the female population, all three concentration ranges (negative, medium, and high) of IL-6 have the highest correlation with high titers (>10 U/ml) of IgM and IgG antibodies. While, in men, all three concentration ranges of IL-6 had the highest correlation with > 10 U/ml IgM antibody titers, but in the case of IgG, the highest correlation between different concentrations of IL-6 was observed with the negative or moderate titers of this antibody and there was an inverse relationship with the high titers of IgG (>10 U/ml). CONCLUSION: As a result, the relationship between different serum levels of cytokine IL-6 with different titers of IgM and IgG antibodies was observed in both male and female populations. In general, it can be concluded that the correlation between different concentrations of IL-6 with different IgM titers was similar in both men and women, but in the case of different IgG titers, this correlation was higher in women than men.


Assuntos
COVID-19 , Humanos , Feminino , Masculino , Interleucina-6 , SARS-CoV-2 , Anticorpos Antivirais , Inflamação , Imunoglobulina G , Imunoglobulina M , Progressão da Doença
18.
PLoS One ; 19(2): e0298393, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38319921

RESUMO

Ocular toxoplasmosis (OT) is caused by protozoan T. gondii. Ophthalmological examination is considered the gold standard for OT diagnosis, and laboratory tests are used for diagnostic confirmation. However, these tests can present different results, which change depending on their basis, on sample type and on patients' clinical alteration. Thus, the aim of the present study is to assess immunodiagnostic and molecular techniques applied in blood, serum and tear fluid to diagnose T. gondii infection in patients seen at an Ophthalmology Clinic. In total, 160 patients were included in the study, 40 of them had OT with active lesions (G1); 40 had OT with healed lesions (G2), 40 had non-toxoplasmic uveitis (G3) and 40 had no ocular alterations (G4). Serum samples were subjected to Immunoenzymatic Assay (ELISA) and to Indirect Immunofluorescence Reaction (IFAT) to search for anti-T. gondii IgM and IgG. Tear fluid samples were analyzed through ELISA for IgA research. All blood and tear fluid samples were subjected to conventional polymerase chain reaction (cPCR) and in a Nested PCR model for T. gondii DNA amplification with targets B1, GRA7 and REP 529. IgG and IgM anti-T. gondii was detected in serum samples from 106 and 15 patients, respectively, when combining ELISA and IFAT results. Anti-T.gondii IgA antibodies were detected in 9.2% of the tear material. Nested PCR with GRA7 target showed higher positivity in blood samples (24.4%); Nested PCR with B1 target showed a higher frequency of positivity in tears (15%). Biological samples of patients with active lesions showed the highest positivity frequencies in all immunodiagnostic assays, as well as in most PCR models. The present results highlighted the need of associating techniques with different fundamentals to confirm OT diagnosis. Furthermore, further tear fluid analyses should be performed to validate this biological material as lesser invasive alternative for the more accurate OT diagnosis.


Assuntos
Toxoplasma , Toxoplasmose Ocular , Humanos , Brasil , Anticorpos Antiprotozoários , Testes Imunológicos , Imunoglobulina G , Imunoglobulina M , Imunoglobulina A/análise
19.
BMC Infect Dis ; 24(1): 168, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326762

RESUMO

BACKGROUND: Leptospirosis is an underdiagnosed infectious disease with non-specific clinical presentation that requires laboratory confirmation for diagnosis. The serologic reference standard remains the microscopic agglutination test (MAT) on paired serum samples. However, reported estimates of MAT's sensitivity vary. We evaluated the accuracy of four index tests, MAT on paired samples as well as alternative standards for leptospirosis diagnosis: MAT on single acute-phase samples, polymerase chain reaction (PCR) with the target gene Lfb1, and ELISA IgM with Leptospira fainei serovar Hurstbridge as an antigen. METHODS: We performed a systematic review of studies reporting results of leptospirosis diagnostic tests. We searched eight electronic databases and selected studies that tested human blood samples and compared index tests with blood culture and/or PCR and/or MAT (comparator tests). For MAT selection criteria we defined a threshold for single acute-phase samples according to a national classification of leptospirosis endemicity. We used a Bayesian random-effect meta-analysis to estimate the sensitivity and specificity of MAT in single acute-phase and paired samples separately, and assessed risk of bias using the Quality Assessment of Studies of Diagnostic Accuracy Approach- 2 (QUADAS-2) tool. RESULTS: For the MAT accuracy evaluation, 15 studies were included, 11 with single acute-phase serum, and 12 with paired sera. Two included studies used PCR targeting the Lfb1 gene, and one included study used IgM ELISA with Leptospira fainei serovar Hurstbridge as antigen. For MAT in single acute-phase samples, the pooled sensitivity and specificity were 14% (95% credible interval [CrI] 3-38%) and 86% (95% CrI 59-96%), respectively, and the predicted sensitivity and specificity were 14% (95% CrI 0-90%) and 86% (95% CrI 9-100%). Among paired MAT samples, the pooled sensitivity and specificity were 68% (95% CrI 32-92%) and 75% (95% CrI 45-93%) respectively, and the predicted sensitivity and specificity were 69% (95% CrI 2-100%) and 75% (2-100%). CONCLUSIONS: Based on our analysis, the accuracy of MAT in paired samples was not high, but it remains the reference standard until a more accurate diagnostic test is developed. Future studies that include larger numbers of participants with paired samples will improve the certainty of accuracy estimates.


Assuntos
Leptospira , Leptospirose , Humanos , Sorogrupo , Teorema de Bayes , Anticorpos Antibacterianos , Testes de Aglutinação/métodos , Sensibilidade e Especificidade , Ensaio de Imunoadsorção Enzimática/métodos , Imunoglobulina M , Reação em Cadeia da Polimerase
20.
Infect Dis Now ; 54(2): 104861, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38316362

RESUMO

OBJECTIVES: To assess the need for screening of transfusion-transmitted infections (TTIs) in blood products, we assessed TTI seroprevalence in blood donors and hospitalized patients. METHODS: We collected 2760 serum samples from three regions of Hangzhou, Ningbo and Huzhou from April 2021 to March 2022, and they tested by enzyme-linked immunosorbent assay (ELISA) for Hepatitis B surface antigen (HBsAg), Hepatitis C (HCV), Treponema pallidum (TP), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Hepatitis E virus (HEV) and Human T-cell lymphotropic virus type 1/2 (HTLV-1/2) antibody levels. RESULTS: Screening test results showed that the positive rates for HBsAg, anti-HCV and anti-TP were 3.01 %, 0.39 % and 0.18 %, respectively. The positive rates for CMV IgM and CMV IgG were 0.76 % and 96.96 %, while the positive rates for EB VCA-IgM and EB EA-IgG were 1.88 % and 10.47 %; those for HEV IgM and HEV IgG were 1.16 % and 26.05 %, while the HTLV-1/2 antibody positive rate was 0.04 %. The positive rates for CMV IgG, EB EA-IgG and HEV IgG in hospitalized patients before transfusion were higher than in volunteer blood donors, and the difference was statistically significant (P < 0.05). The overall co-infection rate was 0.29 %. The positive rates for EB VCA-IgM in the males were significantly higher than in females, and EB VCA-IgM and HEV IgG prevalence varied significantly by age. CONCLUSION: Our data demonstrate the risk of TTI exposure and TTI transmission in the Zhejiang population, which poses a threat to blood safety. It is hoped that expansion of pathogen categories (CMV, EBV, HEV and HTLV-1/2) and blood screening programs will contribute to the future adoption of scientific blood transfusion methods.


Assuntos
Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Reação Transfusional , Masculino , Feminino , Humanos , Doadores de Sangue , Prevalência , Antígenos de Superfície da Hepatite B , Estudos Soroepidemiológicos , Herpesvirus Humano 4 , Transfusão de Sangue , Anticorpos Antivirais , China/epidemiologia , Citomegalovirus , Imunoglobulina G , Imunoglobulina M , Voluntários
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...