RESUMEN
BACKGROUNDS: Progranulin (PGRN) is a growth factor-like molecule with diverse roles in homeostatic and pathogenic processes including the control of immune and inflammatory responses. Pathogenic inflammation is a hallmark of systemic lupus erythematosus (SLE) and elevated serum levels of PGRN has been evaluated as a biomarker of disease activity in SLE. However, the role of PGRN in SLE has not been fully investigated. This study is aimed to determine the potential involvements of PGRN in SLE. METHODS: Wild type (WT) and PGRN knockout (PGRN-/-) C57BL/6 mice received intraperitoneal injection of pristane for induction of a murine model of SLE. Sera were collected every biweekly and levels of anti-dsDNA antibody, IgG, and inflammatory factors were measured. Mice were sacrificed 5 months later and the renal lesions, as well as the proportions of T cell subtypes in the spleen were analyzed. RESULTS: Following exposure to pristane, PGRN-/- mice generated significantly lower levels of anti-dsDNA antibody and IgG relative to WT mice. PGRN-/- mouse kidneys had less IgG and collagen deposition compared with WT mice after pristane injection. CONCLUSION: The results indicate that PGRN participates in inflammatory response and renal damage in pristane induced SLE models, suggesting that PGRN mediates the onset of SLE.
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Anticuerpos Antinucleares , Modelos Animales de Enfermedad , Inmunoglobulina G , Péptidos y Proteínas de Señalización Intercelular , Lupus Eritematoso Sistémico , Ratones Endogámicos C57BL , Ratones Noqueados , Progranulinas , Terpenos , Animales , Lupus Eritematoso Sistémico/inmunología , Ratones , Inmunoglobulina G/sangre , Anticuerpos Antinucleares/sangre , Riñón/metabolismo , Riñón/inmunología , Bazo/inmunología , Bazo/metabolismo , ColágenoRESUMEN
The dynamic interplay between intramammary IgG, formation of antigen-IgG complexes and effector immune cell function is essential for immune homeostasis within the bovine mammary gland. We explore how changes in the recognition and binding of anti-LPS IgG to the glycolipid "functional" core in milk from healthy or clinically diagnosed Escherichia coli (E. coli) mastitis cows' controls endotoxin function. In colostrum, we found a varied anti-LPS IgG repertoire and novel soluble LPS/IgG complexes with direct IgG binding to the LPS glycolipid core. These soluble complexes, absent in milk from healthy lactating cows, were evident in cows diagnosed with E. coli mastitis and correlated with endotoxin-driven inflammation. E. coli mastitis milk displayed a proportional reduction in anti-LPS glycolipid core IgG compared to colostrum. Milk IgG extracts showed that only colostrum IgG attenuated LPS induced endotoxin activity. Furthermore, LPS-stimulated reactive oxygen species (ROS) in milk granulocytes was only suppressed by colostrum IgG, while IgG extracts of neither colostrum nor E. coli mastitis milk influenced N-formylmethionine-leucyl-phenylalanine (fMLP)-stimulated ROS in LPS primed granulocytes. Our findings support bovine intramammary IgG diversity in health and in response to E. coli infection generate milk anti-LPS IgG repertoires that coordinate appropriate LPS innate-adaptive immune responses essential for animal health.
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Calostro , Infecciones por Escherichia coli , Escherichia coli , Glucolípidos , Inmunoglobulina G , Lipopolisacáridos , Mastitis Bovina , Leche , Animales , Bovinos , Femenino , Calostro/inmunología , Calostro/metabolismo , Inmunoglobulina G/inmunología , Inmunoglobulina G/metabolismo , Mastitis Bovina/inmunología , Mastitis Bovina/microbiología , Escherichia coli/inmunología , Lipopolisacáridos/inmunología , Leche/inmunología , Glucolípidos/metabolismo , Glucolípidos/inmunología , Infecciones por Escherichia coli/inmunología , Endotoxinas/inmunología , Endotoxinas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Granulocitos/inmunología , Granulocitos/metabolismo , Unión Proteica , Glándulas Mamarias Animales/inmunología , Glándulas Mamarias Animales/metabolismoRESUMEN
Limited research suggests that certain viruses reactivate in severe-acute-respiratory-syndrome-coronavirus 2 infection, contributing to the development of postacute sequelae of COVID-19 (PASC). We examined 1083 infected individuals from a population-based cohort, and assessed differences in plasma immunoglobulin (Ig)G and immunoglobulin A levels against Epstein-Barr virus (EBV), cytomegalovirus, varicella zoster virus (VZV), BK polyomavirus, KI polyomavirus, WU polyomavirus (WUPyV), respiratory syncytial virus, and Adv-36 according to the severity of previous COVID-19 and PASC history. Individuals who had experienced severe COVID-19 had higher antibody responses to latent viruses. Ever PASC, active persistent PASC, and PASC with neuropsychiatric symptoms were associated with higher immnoglobulin G to EBV early antigen-diffuse, VZV, and WUPyV even among individuals without previous severe COVID-19.
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Anticuerpos Antivirales , COVID-19 , Inmunoglobulina G , Humanos , COVID-19/inmunología , COVID-19/virología , Anticuerpos Antivirales/sangre , Masculino , Femenino , Persona de Mediana Edad , Inmunoglobulina G/sangre , Adulto , Índice de Severidad de la Enfermedad , Anciano , SARS-CoV-2/inmunología , Inmunoglobulina A/sangre , Formación de Anticuerpos , Síndrome Post Agudo de COVID-19 , Estudios de CohortesRESUMEN
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral zoonosis caused by a Nairovirus, Crimean-Congo hemorrhagic fever virus (CCHFV). Despite its wide geographical distribution, the epidemiology of CCHF in northern Africa is incompletely understood and its occurrence in Algeria is virtually unknown. The present survey aimed to determine the prevalence of CCHF antibodies and to identify the potential risk factors associated with CCHFV seropositivity among the one-humped camel (Camelus dromedarius) in southern Algeria. A total of 269 camels selected randomly from slaughterhouses in three wilayas were employed in the study. Sera sampled were tested for the presence of CCHFV-specific IgG antibodies using enzyme-linked immunosorbent assay (ELISA). CCHFV seropositivity was recorded in 255 out of 269 camels accounting for a prevalence rate of 94.8% (95%CI = 92.14-97.45). The seroprevalence by origin was determined to be 97% (193/199) in imported camels and 86% (49/57) in local ones (p > 0.25). Tick presence (OR = 12.35, 95%CI = 1.41-107.43, p < 0.05) was recorded as the only potential risk factor for contracting CCHFV. This study shows for the first time that camels are exposed to CCHFV in Algeria with a significantly high seroprevalence. It also underlines the need for further research to investigate the broader extent of circulating CCHFV in the country, whether in humans, animals, or ticks.
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Anticuerpos Antivirales , Camelus , Ensayo de Inmunoadsorción Enzimática , Virus de la Fiebre Hemorrágica de Crimea-Congo , Fiebre Hemorrágica de Crimea , Animales , Camelus/virología , Argelia/epidemiología , Fiebre Hemorrágica de Crimea/epidemiología , Fiebre Hemorrágica de Crimea/veterinaria , Fiebre Hemorrágica de Crimea/virología , Estudios Seroepidemiológicos , Virus de la Fiebre Hemorrágica de Crimea-Congo/inmunología , Virus de la Fiebre Hemorrágica de Crimea-Congo/aislamiento & purificación , Masculino , Femenino , Factores de Riesgo , Anticuerpos Antivirales/sangre , Ensayo de Inmunoadsorción Enzimática/veterinaria , Prevalencia , Enfermedades por Picaduras de Garrapatas/epidemiología , Enfermedades por Picaduras de Garrapatas/veterinaria , Enfermedades por Picaduras de Garrapatas/virología , Inmunoglobulina G/sangre , Garrapatas/virologíaRESUMEN
Sporotrichosis diagnosis involves a series of analyses, including culture and antibody detection in serum samples. Serologic methods may sometimes yield false-negative or false-positive results, leading to inaccurate diagnoses. This study assessed specific patient groups in which antibody detection of different isotypes and subclasses may lack sensitivity. An enzyme-linked immunosorbent assay (ELISA) with Sporothrix brasiliensis exoantigens was used to investigate IgM, IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgA1 and IgA2 antibodies in human serum samples. Eighty serum samples from patients with different sporotrichosis clinical manifestations, including cutaneous forms with and without hypersensitivity manifestations, extracutaneous forms (bone, ocular, meningeal and pulmonary), disseminated cutaneous forms and disseminated forms in individuals living with HIV/AIDS, diabetics and alcoholics, were evaluated. The ELISA sensitivities in the detection of different antibodies ranged from 0.85 to 0.60 for the detection of IgG2 and IgG3, respectively. The antibodies with higher area under ROC curves were IgG2, IgG, IgA and IgA1. There were no significant differences in the immunological reactivity of the tested antibodies among different clinical forms of sporotrichosis. The data revealed a higher likelihood of a false-negative outcome in patients with lesions in the nasal mucosa regarding the detection of IgM and a lower likelihood in patients with lymphocutaneous sporotrichosis regarding the detection of IgG3. Patients with hypersensitivity manifestations had a 3.71 odds ratio to yield negative results in total IgG detection. In conclusion, we identified specific patient groups in which antibody detection may lack sensitivity, thus contributing to a better understanding of the diagnostic challenges associated with this condition.
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Anticuerpos Antifúngicos , Ensayo de Inmunoadsorción Enzimática , Sensibilidad y Especificidad , Sporothrix , Esporotricosis , Humanos , Esporotricosis/inmunología , Esporotricosis/diagnóstico , Anticuerpos Antifúngicos/sangre , Sporothrix/inmunología , Sporothrix/clasificación , Masculino , Femenino , Adulto , Persona de Mediana Edad , Isotipos de Inmunoglobulinas/sangre , Isotipos de Inmunoglobulinas/inmunología , Inmunoglobulina G/sangre , Anciano , Adulto Joven , Antígenos Fúngicos/inmunología , Antígenos Fúngicos/sangre , Inmunoglobulina A/sangre , Inmunoglobulina M/sangreRESUMEN
Patients undergoing hemodialysis are particularly vulnerable to severe outcomes of SARS-CoV-2 infection, with mortality rates higher than that of the general population. Vaccination reduces the risk of adverse outcomes, with booster doses being particularly beneficial. However, limited data are available on the effectiveness of subsequent vaccinations or their effect on increasing antibody levels. This single-center study aimed to investigate changes in SARS-CoV-2 IgG antibody titers following the fourth vaccination among 28 patients undergoing hemodialysis. Blood tests were conducted at various intervals post-vaccination, with a focus on identifying factors associated with antibody levels. The IgG antibody levels rapidly increased by Day 7 post-vaccination, with a median time to peak of 11 days. Antibody titers tended to be higher in male patients than in female patients. This study sheds light on the immune response to the fourth vaccination in patients undergoing hemodialysis. As this study included a small sample size, with a short observation period, further research is warranted to comprehensively understand the effectiveness of vaccination and the benefits of additional doses of vaccine.
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Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Inmunoglobulina G , Diálisis Renal , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Masculino , Femenino , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/prevención & control , SARS-CoV-2/inmunología , Anciano , Glicoproteína de la Espiga del Coronavirus/inmunología , Persona de Mediana Edad , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Japón/epidemiología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunación , Anciano de 80 o más Años , Inmunización Secundaria , Adulto , Pueblos del Este de AsiaRESUMEN
INTRODUCTION: Due to the cross-reactivity between SARS-CoV-2 and common human coronaviruses, previous infections with these viruses could contribute to serological or cellular cross-protection against severe COVID-19. However, protective immunity may not develop, or pre-existing immunity could increase COVID-19 severity. OBJECTIVE: To determine the seroprevalence of IgG antibodies against HCoV-NL63 and HCoV-HKU1 and correlate previous exposure with COVID-19 signs in patients from Villavicencio. MATERIALS AND METHODS: A cross-sectional retrospective study was conducted. ELISA technique was used to search for IgG antibodies against HCoV-NL3 and HCoV-HKU1 in patients with positive RT-qPCR results for SARS-CoV-2. Patients were grouped according to COVID-19 clinical characteristics in four groups: group 1: asymptomatic (n = 23); group 2: hospitalized (n = 24); group 3: intensive care units (n = 24), and group 4: dead (n = 22). RESULTS: The overall seroprevalence of IgG antibodies against HCoV was 74.2% (n = 69; 95% CI: 65.3-83.1), with 66.7% of HCoV-NL63 (n = 62; 95% CI: 57,1-76,2), and 25.8% of HCoV-HKU1 (n = 24; 95% CI: 16,9-34,7). Based on crosstab analysis, prior exposure to HCoV-NL63 was associated with protection against severe COVID-19 (p = 0.042; adjusted OR = 0.159; 95% CI: 0.027-0.938), and previous coinfection of HCoV-NL63 and HCoVHKU1 was considered a positive association to severe COVID-19 (p = 0.048; adjusted OR = 16.704; 95% CI: 1.020 - 273.670). CONCLUSION: To our knowledge, this is the first study addressing seroprevalence of HCoV IgG antibodies in Colombia and Latin America. Previous exposure to HCoV-NL63 could protect against severe COVID-19, whereas patients with underlying HCoV-NL63 and HCoVHKU1 coinfection could be hospitalized with severe signs of COVID-19.
Introducción: Debido a la reactividad cruzada entre SARS-CoV-2 y los coronavirus humanos comunes, las infecciones previas con estos virus podrían contribuir a la protección cruzada serológica o celular contra la COVID-19 grave. Sin embargo, la inmunidad protectora puede no desarrollarse o la inmunidad preexistente podría generar COVID-19 grave. Objetivo: Determinar la seroprevalencia de anticuerpos IgG frente a HCoV-NL63 y HCoVHKU1, y correlacionar su previa exposición con los signos de COVID-19 en pacientes de Villavicencio. Materiales y métodos: Se realizó un estudio retrospectivo observacional analítico y transversal. Se utilizó la técnica ELISA para buscar anticuerpos IgG contra HCoV-NL3 y HCoV-HKU1 en pacientes con resultado positivo de RT-qPCR para SARS-CoV-2. Los pacientes se agruparon según los signos de COVID-19 en cuatro grupos: grupo 1: asintomáticos (n = 23); grupo 2: hospitalizados (n = 24); grupo 3: unidad de cuidados intensivos (n = 24), y grupo 4: fallecidos (n = 22). Resultados: La seroprevalencia general de IgG anti-HCoV fue de 74.2 % (n = 69; IC95%: 65,3-83,1), con 66,7 % de HCoV-NL63 (n = 62; IC95% :57,1-76,2) y 25,8 % de HCoV-HKU1 (n = 24; [IC95%:16,9-34,7). Según el análisis de las tablas de contingencia, la exposición previa a HCoV-NL63 se asoció con protección de una COVID-19 grave (p = 0,042; OR ajustado = 0,159; IC95%: 0,027-0,938) y la previa coinfección de HCoV-NL63 y HCoV-HKU1 se asoció con padecimiento de signos clínicos graves por COVID-19 (p = 0,048; OR ajustado = 16,704; IC95%: 1,020- 73,670). Conclusión: Según la literatura revisada hasta la fecha, este es el primer estudio sobre la seroprevalencia de anticuerpos IgG de HCoV en Colombia y Latinoamérica. La exposición previa a HCoV-NL63 podría proteger contra la COVID-19 grave, mientras que los pacientes con coinfección subyacente de HCoV-NL63 y HCoV-HKU1 podrían resultar hospitalizados con signos graves de COVID-19.
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Anticuerpos Antivirales , COVID-19 , Coronavirus Humano NL63 , Inmunoglobulina G , SARS-CoV-2 , Humanos , Estudios Seroepidemiológicos , COVID-19/epidemiología , COVID-19/inmunología , Colombia/epidemiología , Estudios Transversales , Estudios Retrospectivos , Coronavirus Humano NL63/inmunología , Masculino , Persona de Mediana Edad , Femenino , Adulto , Inmunoglobulina G/sangre , Anticuerpos Antivirales/sangre , SARS-CoV-2/inmunología , Anciano , Adulto Joven , AdolescenteRESUMEN
BACKGROUND: Elevated serum immunoglobulin G4 (IgG4) concentrations are one of the characteristic findings in IgG4-related disease (IgG4-RD). This study investigated the frequency of elevated serum IgG4 levels and associated factors in a general Japanese population. METHODS: Serum IgG4 concentrations were measured in 1,201 residents of Ishikawa prefecture who underwent general medical examinations. Factors associated with elevated serum IgG4 concentrations were assessed by logistic regression analysis. Participants with elevated serum IgG4 were subjected to secondary examinations. RESULTS: The mean serum IgG4 concentration was 44 mg/dL, with 42 (3.5%) participants having elevated serum IgG4 levels. Age- and sex-adjusted logistic regression analyses showed that male sex, older age, and lower intake of lipids and polyunsaturated fatty acids and higher intake of carbohydrates in daily diet were associated with elevated serum IgG4 concentration. Subgroup analyses in men showed that older age, lower estimated glomerular filtration rates based on serum cystatin C (eGFR-cysC) levels, and higher hemoglobin A1c (HbA1c) levels were associated with elevated serum IgG4 concentration. Analyses in women showed that lower intake of lipids and fatty acids and higher intake of carbohydrates were significantly associated with elevated serum IgG4 concentration. One of the 15 participants who underwent secondary examinations was diagnosed with possible IgG4-related retroperitoneal fibrosis. CONCLUSIONS: Elevated serum IgG4 levels in a Japanese general population were significantly associated with older age, male gender, and dietary intake of nutrients, with some of these factors identical to the epidemiological features of IgG4-RD.
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Inmunoglobulina G , Humanos , Masculino , Femenino , Inmunoglobulina G/sangre , Persona de Mediana Edad , Japón/epidemiología , Anciano , Adulto , Enfermedad Relacionada con Inmunoglobulina G4/sangre , Enfermedad Relacionada con Inmunoglobulina G4/epidemiología , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Anciano de 80 o más Años , Pueblos del Este de AsiaRESUMEN
BACKGROUND: To report a case of IgG4-related pachymeningitis presenting with cystic lesions mimicking neurocysticercosis. CASE PRESENTATION: A 40-year-old female patient with tetraparesis, dysphagia and dysphonia was evaluated with clinical examination, magnetic resonance imaging, and meningeal biopsy. Magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement involving the cranial, cervical, thoracic, and lumbar segments with spinal cord compression and cystic lesions. CSF immunology was initially positive for cysticercus cellulosae. After disease progression a meningeal biopsy was compatible with IgG4 related disease. The patient had partial response to rituximab and needed multiple surgical procedures for spinal cord decompression and CSF shunting. CONCLUSIONS: This case highlights the possibility of IgG4-related disease in patients with diffuse pachymeningitis causing spinal cord compression, even with cystic lesions on MRI. Diagnosis of IgG4-related pachymeningitis is paramount due to the possibility of treatment response to immunotherapy, particularly to anti-CD20 agents.
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Enfermedad Relacionada con Inmunoglobulina G4 , Meningitis , Neurocisticercosis , Compresión de la Médula Espinal , Humanos , Femenino , Adulto , Meningitis/diagnóstico , Neurocisticercosis/complicaciones , Neurocisticercosis/diagnóstico , Neurocisticercosis/diagnóstico por imagen , Compresión de la Médula Espinal/etiología , Diagnóstico Diferencial , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/complicaciones , Imagen por Resonancia Magnética , Inmunoglobulina G/sangre , Inmunoglobulina G/líquido cefalorraquídeoRESUMEN
The gut microbiome plays an essential role in host immune responses, including allergic reactions. However, commensal gut microbiota is extremely sensitive to antibiotics and excessive usage can cause microbial dysbiosis. Herein, we investigated how changes in the gut microbiome induced by ampicillin affected the production of IgG1 and IgG2a antibodies in mice subsequently exposed to Anisakis pegreffii antigens. Ampicillin treatment caused a notable change in the gut microbiome as shown by changes in both alpha and beta diversity indexes. In a 1-dimensional immunoblot using Anisakis-specific anti-mouse IgG1, a 56-kDa band corresponding to an unnamed Anisakis protein was detected using mass spectrometry analysis only in ampicillin-treated mice. In the Anisakis-specific anti-mouse IgG2a-probed immunoblot, a 70-kDa band corresponding to heat shock protein 70 (HSP70) was only detected in ampicillin-treated and Anisakis-immunized mice. A 2-dimensional immunoblot against Anisakis extract with immunized mouse sera demonstrated altered spot patterns in both groups. Our results showed that ampicillin treatment altered the gut microbiome composition in mice, changing the immunization response to antigens from A. pegreffii. This research could serve as a basis for developing vaccines or allergy immunotherapies against parasitic infections.
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Ampicilina , Anisakis , Microbioma Gastrointestinal , Inmunoglobulina G , Animales , Anisakis/inmunología , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/inmunología , Ampicilina/farmacología , Ratones , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangre , Antígenos Helmínticos/inmunología , Femenino , Anisakiasis/inmunología , Anisakiasis/parasitología , Anticuerpos Antihelmínticos/inmunología , InmunizaciónRESUMEN
Seroepidemiological characteristics of human papillomavirus (HPV) in community residents reflect natural infection and can guide the reform of vaccination programs. A population-based serological survey was conducted in Guangdong Province. Serum anti-HPV IgG antibody levels were determined by an ELISA. Neutralizing antibodies against HPV6, 11, 16, and 18 were detected via a pseudovirus-based neutralization assay (PBNA). A total of 5122 serum samples were collected from community residents, including 1989 males and 3133 females, in three cities of Guangdong Province. The rate of HPV IgG antibody positivity in females was 5.39% (95% CI: 4.6-6.2), which was greater than that in males (2.36%; 95% CI: 1.7-3.1). HPV IgG antibodies were more frequently detected in females aged 51-60 years (11.30%; 95% CI: 7.6-16.0), whereas in males, the detection increased with age and reached 4.94% (95% CI: 2.8-6.9) in the group aged ≥71 years. The seropositivity of neutralizing antibodies against HPV6 and 11 was greater than that against HPV16 and 18. The serum neutralizing antibody titers in individuals who received three doses of a vaccine were 7- to 12-fold greater than those in individuals who did not receive the vaccine. The neutralizing antibody titers slightly decreased within 40 months and ranged from 0.038 to 0.057 log ED50 per month. A moderate consistency between the HPV ELISA and PBNA results was observed (Kappa score = 0.49, r = 0.249, 0.635, 0.382, and 0.466 for HPV6, 11, 16, and 18, respectively). The HPV seropositivity rate among healthy residents of Guangdong Province was found to be low among children and adolescents and to increase with age. The serum neutralizing antibody titers were significantly greater in the vaccine group than that in the control group, and this difference persisted over time, which indicated promising protection against HPV infection.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina G , Infecciones por Papillomavirus , Humanos , China/epidemiología , Estudios Seroepidemiológicos , Masculino , Femenino , Anticuerpos Antivirales/sangre , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/virología , Adulto , Persona de Mediana Edad , Anticuerpos Neutralizantes/sangre , Adulto Joven , Anciano , Adolescente , Niño , Inmunoglobulina G/sangre , Preescolar , Vacunas contra Papillomavirus/inmunología , Vacunas contra Papillomavirus/administración & dosificación , Papillomaviridae/inmunología , Papillomaviridae/genética , Papillomaviridae/clasificación , Pruebas de Neutralización , Vacunación/estadística & datos numéricos , Anciano de 80 o más Años , Lactante , Virus del Papiloma HumanoRESUMEN
Antibody-dependent complement activation plays a key role in the natural human immune response to infections. Currently, the understanding of which antibody-antigen combinations drive a potent complement response on bacteria is limited. Here, we develop an antigen-agnostic approach to stain and single-cell sort human IgG memory B cells recognizing intact bacterial cells, keeping surface antigens in their natural context. With this method we successfully identified 29 antibodies against K. pneumoniae, a dominant cause of hospital-acquired infections with increasing antibiotic resistance. Combining genetic tools and functional analyses, we reveal that the capacity of antibodies to activate complement on K. pneumoniae critically depends on their antigenic target. Furthermore, we find that antibody combinations can synergistically activate complement on K. pneumoniae by strengthening each other's binding in an Fc-independent manner. Understanding the molecular basis of effective complement activation by antibody combinations to mimic a polyclonal response could accelerate the development of antibody-based therapies against problematic infections.
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Anticuerpos Antibacterianos , Activación de Complemento , Inmunoglobulina G , Klebsiella pneumoniae , Humanos , Activación de Complemento/inmunología , Anticuerpos Antibacterianos/inmunología , Klebsiella pneumoniae/inmunología , Inmunoglobulina G/inmunología , Linfocitos B/inmunología , Células B de Memoria/inmunologíaRESUMEN
Limited knowledge exists on the quality of polyclonal antibody responses generated following Marburg virus (MARV) infection and its evolution in survivors. In this study, we evaluate MARV proteome-wide antibody repertoire longitudinally in convalescent phase approximately every six months for five years following MARV infection in ten human survivors. Differential kinetics were observed for IgM vs IgG vs IgA epitope diversity, antibody binding, antibody affinity maturation and Fc-receptor interaction to MARV proteins. Durability of MARV-neutralizing antibodies is low in survivors. MARV infection induces a diverse epitope repertoire with predominance against GP, VP40, VP30 and VP24 that persisted up to 5 years post-exposure. However, the IgM and IgA repertoire declines over time. Within MARV-GP, IgG recognize antigenic sites predominantly in the amino-terminus, wing domain and GP2-heptad repeat. Interestingly, MARV infection generates robust durable FcɣRI, FcɣRIIA and FcɣRIIIA IgG-Fc receptor interactions. Immunization with immunodominant MARV epitopes reveals conserved wing region between GP1 and GP2, induces neutralizing antibodies against MARV. These findings demonstrate that MARV infection generates a diverse, long-lasting, non-neutralizing, IgG antibody repertoire that perturbs disease by FcɣR activity. This information, along with discovery of neutralizing immunogen in wing domain, could aid in development of effective therapeutics and vaccines against Marburg virus.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Enfermedad del Virus de Marburg , Marburgvirus , Proteoma , Marburgvirus/inmunología , Humanos , Enfermedad del Virus de Marburg/inmunología , Enfermedad del Virus de Marburg/virología , Anticuerpos Antivirales/inmunología , Anticuerpos Neutralizantes/inmunología , Proteoma/inmunología , Femenino , Vacunas Virales/inmunología , Inmunoglobulina G/inmunología , Masculino , Epítopos/inmunología , Adulto , Inmunoglobulina M/inmunología , Persona de Mediana Edad , Estudios Longitudinales , Inmunoglobulina A/inmunología , Desarrollo de Vacunas , Proteínas del Envoltorio Viral/inmunologíaRESUMEN
Introduction: Pre-existent pools of coronavirus-specific or cross-reactive T cells were shown to shape the development of cellular and humoral immune responses after primary mRNA vaccination against SARS-CoV-2. However, the cellular determinants of responses to booster vaccination remain incompletely understood. Therefore, we phenotypically and functionally characterized spike antigen-specific T helper (Th) cells in healthy, immunocompetent individuals and correlated the results with cellular and humoral immune responses to BNT162b2 booster vaccination over a six-month period. Methods: Blood of 30 healthy healthcare workers was collected before, 1, 3, and 6 months after their 3rd BNT162b2 vaccination. Whole blood was stimulated with spike peptides and analyzed using flow cytometry, a 13-plex cytokine assay, and nCounter-based transcriptomics. Results: Spike-specific IgG levels at 1 month after booster vaccination correlated with pre-existing CD154+CD69+IFN-γ+CD4+ effector memory cells as well as spike-induced IL-2 and IL-17A secretion. Early post-booster (1-month) spike IgG levels (r=0.49), spike-induced IL2 (r=0.58), and spike-induced IFNγ release (r=0.43) correlated moderately with their respective long-term (6-month) responses. Sustained robust IgG responses were significantly associated with S-specific (CD69+±CD154+±IFN-γ+) Th-cell frequencies before booster vaccination (p=0.038), especially double/triple-positive type-1 Th cells. Furthermore, spike IgG levels, spike-induced IL2 release, and spike-induced IFNγ release after 6 months were significantly associated with increased IL2 & IL4, IP10 & MCP1, and IFNγ & IP10 levels at 1 month post-booster, respectively. On the transcriptional level, induction of pathways associated with both T-cell proliferation and antigen presentation was indicative of sustained spike-induced cytokine release and spike-specific IgG production 6 months post-booster. Using support vector machine models, pre-booster spike-specific T-cell frequencies and early post-booster cytokine responses predicted sustained (6-month) responses with F1 scores of 0.80-1.00. Discussion: In summary, spike-specific Th cells and T-cellular cytokine signatures present before BNT162b2 booster vaccination shape sustained adaptive cellular and humoral responses post-booster. Functional T-cell assays might facilitate early identification of potential non-responders.
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Anticuerpos Antivirales , Vacuna BNT162 , COVID-19 , Citocinas , Inmunidad Humoral , Inmunización Secundaria , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Linfocitos T Colaboradores-Inductores , Humanos , Citocinas/metabolismo , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , COVID-19/inmunología , COVID-19/prevención & control , Masculino , SARS-CoV-2/inmunología , Adulto , Femenino , Glicoproteína de la Espiga del Coronavirus/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Persona de Mediana Edad , Linfocitos T Colaboradores-Inductores/inmunología , Vacunas contra la COVID-19/inmunología , Inmunidad Celular , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , VacunaciónRESUMEN
BACKGROUND: Ankylosing spondylitis (AS) has been known to have auto-inflammatory nature; hence, the efficacy of autoantibodies is low. However, studies on autoantibodies are ongoing, with some studies showing associations. Previous studies showed that anti-protein phosphatase magnesium-dependent 1A (PPM1A) IgG was increased in patients with AS and associated with radiographic progression. However, the diagnostic usefulness was limited due to relatively low sensitivity and specificity. This pilot study evaluated the diagnostic utility of anti-PPM1A-IgM and anti-PPM1A-IgG in patients with active AS. METHODS: Serum samples were obtained from the registry cohort of a single tertiary center in Korea. Serum levels of anti-PPM1A-IgG/IgM were measured by direct ELISA. Receiver operating characteristic (ROC) analysis was used to predict the diagnostic sensitivity and specificity of serum anti-PPM1A-IgG/IgM. RESULTS: Samples were collected from 28 patients with active AS, 16 healthy controls (HCs), and 28 patients with rheumatoid arthritis (RA). Although total serum IgM was lower in the RA and AS groups than in the HC group, anti-PPM1A-IgM was significantly lower in the AS group than in the other groups. In evaluating the diagnostic utility of anti-PPM1A-IgG/IgM for AS patients compared with HCs, the area under the curve (AUC) of anti-PPM1A-IgM was 0.998 (sensitivity 96.4%, specificity 100.0%). When ROC analysis of anti-PPM1A-IgM for AS patients compared with RA patients was conducted, sensitivity was 78.6% and specificity was 71.4%, with an AUC of 0.839. CONCLUSION: Decreased anti-PPM1A-IgM levels in AS patients suggests a potential role for anti-PPM1A-IgM in the diagnosis of active AS.
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Autoanticuerpos , Biomarcadores , Inmunoglobulina M , Proteína Fosfatasa 2C , Curva ROC , Sensibilidad y Especificidad , Espondilitis Anquilosante , Humanos , Espondilitis Anquilosante/sangre , Espondilitis Anquilosante/diagnóstico , Masculino , Biomarcadores/sangre , Femenino , Adulto , Inmunoglobulina M/sangre , Autoanticuerpos/sangre , Proteína Fosfatasa 2C/sangre , Persona de Mediana Edad , Inmunoglobulina G/sangre , Estudios de Casos y Controles , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Proyectos Piloto , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
Immunoglobulin G (IgG) is the main isotype of antibody in human blood. IgG consists of four subclasses (IgG1 to IgG4), encoded by separate constant region genes within the Ig heavy chain locus (IGH). Here, we report a genome-wide association study on blood IgG subclass levels. Across 4334 adults and 4571 individuals under 18 years, we discover ten new and identify four known variants at five loci influencing IgG subclass levels. These variants also affect the risk of asthma, autoimmune diseases, and blood traits. Seven variants map to the IGH locus, three to the Fcγ receptor (FCGR) locus, and two to the human leukocyte antigen (HLA) region, affecting the levels of all IgG subclasses. The most significant associations are observed between the G1m (f), G2m(n) and G3m(b*) allotypes, and IgG1, IgG2 and IgG3, respectively. Additionally, we describe selective associations with IgG4 at 16p11.2 (ITGAX) and 17q21.1 (IKZF3, ZPBP2, GSDMB, ORMDL3). Interestingly, the latter coincides with a highly pleiotropic signal where the allele associated with lower IgG4 levels protects against childhood asthma but predisposes to inflammatory bowel disease. Our results provide insight into the regulation of antibody-mediated immunity that can potentially be useful in the development of antibody based therapeutics.
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Asma , Estudio de Asociación del Genoma Completo , Inmunoglobulina G , Polimorfismo de Nucleótido Simple , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina G/genética , Adulto , Femenino , Masculino , Asma/genética , Asma/inmunología , Asma/sangre , Niño , Adolescente , Receptores de IgG/genética , Persona de Mediana Edad , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas Pesadas de Inmunoglobulina/sangre , Alelos , Adulto Joven , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/sangre , Cromosomas Humanos Par 17/genética , Predisposición Genética a la Enfermedad , Antígenos HLA/genética , Antígenos HLA/inmunología , Proteínas de la MembranaRESUMEN
OBJECTIVE: The objective of this study is to investigate the presence of astrocyte antibodies in patients, excluding aquaporin-4 or glial fibrillary acidic protein (GFAP) antibodies, while evaluating associated biomarkers and pathologies. METHODS: Patient serum and cerebrospinal fluid (CSF) were tested for antibodies using tissue- and cell-based assays. Neurofilament light chain (NFL) and GFAP in the CSF were detected using single-molecule array (SIMOA). RESULTS: 116 patients accepted SIMOA. Fifteen functional neurological disorders patients without antibodies were designated as controls. Thirty-five patients were positive for astrocyte antibodies (Anti-GFAP: 7; Anti-AQP4: 7; unknown antibodies: 21, designed as the double-negative group, DNAP). The most frequent phenotype of DNAP was encephalitis (42.9%), followed by myelitis (23.8%), movement disorders (19.0%), and amyotrophic lateral sclerosis-like (ALS-like) disease (14.2%). The levels of CSF GFAP and NFL in DNAP were higher than in the control (GFAP: 1967.29 [776.60-13214.47] vs 475.38 [16.80-943.60] pg/mL, p < 0.001; NFL: 549.11 [162.08-2462.61] vs 214.18 [81.60-349.60] pg/mL, p = 0.002). GFAP levels decreased in DNAP (n = 5) after immunotherapy (2446.75 [1583.45-6277.33] vs 1380.46 [272.16-2005.80] pg/mL, p = 0.043), while there was no difference in NFL levels (2273.78 [162.08-2462.61] vs 890.42 [645.06-3168.06] pg/mL, p = 0.893). Two brain biopsy patterns were observed: one exhibited prominent tissue proliferation and hypertrophic astrocytes, with local loss of astrocytes, while the other showed severe astrocyte depletion with loss of neurofilaments around the vessels. Eighteen patients received immunotherapy, and improved except one with ALS-like symptoms. We identified anti-vimentin in this patient. DISCUSSION: There are unidentified astrocyte antibodies. The manifestations of double-negativity are heterogeneous; nevertheless, the pathology and biomarkers remain consistent with astrocytopathy. Immunotherapy is effective.
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Acuaporina 4 , Astrocitos , Biomarcadores , Proteína Ácida Fibrilar de la Glía , Inmunoglobulina G , Humanos , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Proteína Ácida Fibrilar de la Glía/inmunología , Femenino , Masculino , Acuaporina 4/inmunología , Persona de Mediana Edad , Astrocitos/inmunología , Astrocitos/metabolismo , Astrocitos/patología , Estudios Retrospectivos , Adulto , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/sangre , Anciano , Inmunoglobulina G/líquido cefalorraquídeo , Inmunoglobulina G/sangre , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Proteínas de Neurofilamentos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Autoanticuerpos/sangre , Adulto Joven , AdolescenteRESUMEN
BACKGROUND: Asymptomatic carriage of infected red blood cells (iRBCs) can be prevalent in communities regardless of transmission patterns and can occur with infection of different Plasmodium species. Clinical immunity dampens the inflammatory responses leading to disease symptoms in malaria. The aim of this study was to define the immunological correlates of asymptomatic carriage of Plasmodium falciparum in a highly exposed population. METHODS: 142 asymptomatic Plasmodium-infected individuals greater than 2 years of age without fever (body temperature <37.5 â) were followed weekly for 10 weeks before being treated with artemisinin-based combination therapy (ACT). Plasma levels of 38 cytokines were measured at baseline by Luminex and the quantity and growth inhibitory activities of circulating parasite-reactive antibodies measured. The Plasmodium antigen tested included P. falciparum merozoite extract (ME) and schizont extract (SE), and the recombinant proteins erythrocyte binding antigen 175 (EBA-175) and merozoite surface protein 1 (MSP-119). RESULTS: Median levels of IgG against P. falciparum EBA-175 and MSP-119 at baseline were significantly higher in those older than 20 years of age compared with the younger age group and appeared to correlate with better parasite control. Amongst all participants there were no discernible changes in IgG levels over time. Parasite density was higher in the younger age group and associated with IL-10, TNF and MCP-1 levels. A balanced IL-10:TNF ratio was associated with asymptomatic malaria regardless of age, and balanced ratios of IL-10/TNF and IL-10/IFN-γ were the only significant correlate of maintenance of asymptomatic malaria over the course of the study in individuals 20 years of age and younger. CONCLUSION: The above findings indicate that asymptomatic carriage of P. falciparum in children living in a hyperendemic area occurs independently of IgG but is associated with a balanced inflammatory cytokine ratio.
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Portador Sano , Citocinas , Inmunoglobulina G , Malaria Falciparum , Plasmodium falciparum , Humanos , Plasmodium falciparum/inmunología , Plasmodium falciparum/fisiología , Niño , Inmunoglobulina G/sangre , Preescolar , Malaria Falciparum/epidemiología , Malaria Falciparum/inmunología , Malaria Falciparum/parasitología , Citocinas/sangre , Adolescente , Masculino , Femenino , Portador Sano/epidemiología , Adulto Joven , Infecciones Asintomáticas/epidemiología , Anticuerpos Antiprotozoarios/sangre , Enfermedades Endémicas/estadística & datos numéricosRESUMEN
OBJECTIVE: Aim: To estimate the differences between patients with celiac disease based on symptoms, diagnosis, treatment, and follow-up. PATIENTS AND METHODS: Materials and Methods: A retrospective cross-sectional study carried out between July 1, 2022 and April 2023, enrolling 200 patients from different provinces of central and south Iraq with Celia disease, whose diagnosis depended on a specialized physician according to WHO guidelines with long-term follow-up. Participants were following up for three to six months in private clinics. Survey was written in English, and the questionnaire form contains 13 fields divided into three sections. Diagnosis of Celia before and after treatment parameters: Tissue Transglutaminase Antibody, IgG, Serum (tTg-Ig G), and tTg-IgA levels the fourth part included a glutin-free diet and symptomatic treatment. RESULTS: Results: Females and ages below 20 were most affected. 176(88%) patients had detectable tTG levels; after 3 months, 72(36.0%) patients had an increase in their body weight but less than 5 kg, while 14(7.0%) of the patients showed an increase of more than 5 kg. But after 6 months, 73(36.5%) patients had an increase in their body weight less than 5 kg, while 45(22.5%) of patients showed an increase of more than 5 kg. CONCLUSION: Conclusions: Celiac patient profile in central Iraq is not different from that in other parts of the world, with typical patient being female and under 30 years of age. The study highlighted to a certain degree that a gluten-free diet can have a modest and promising positive impact on BMI in some patients.
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Enfermedad Celíaca , Humanos , Enfermedad Celíaca/dietoterapia , Enfermedad Celíaca/terapia , Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/diagnóstico , Irak/epidemiología , Femenino , Masculino , Estudios Transversales , Estudios Retrospectivos , Adulto , Adulto Joven , Adolescente , Dieta Sin Gluten , Persona de Mediana Edad , Transglutaminasas/inmunología , Niño , Inmunoglobulina G/sangreRESUMEN
BACKGROUND: Seroprevalence studies have proven to be an important tool in tracking the progression of the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to measure the seroprevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the general population of Kosovo by gender, age group and region and among asymptomatic people. METHOD: The Institute of Public Health of Kosovo conducted a cross-sectional population-based survey, aligned with the protocols of the WHO Unity Studies, from the beginning of May to the end of June 2021. RESULTS: The survey covered a total of 2204 people with a response rate of 91.8% (41.9% [923] males and 51.2% [1281] females). In May to June 2021, the prevalence of antibodies in the overall population (IgG antibodies ≥ 1.1) was 37.0%. Seroprevalence was 34.4% in men and 38.9% in women (p < 0.05), with the highest percentage (48.7%) found in the 60-69 years' age group. The overall prevalence of acute IgM antibodies (IgM ≥ 1.1) was 1% (95% CI: 0.7%-1.5%), with no significant difference between genders and the highest prevalence among participants of 60-69 years of age (1.6%; 95% CI: 0.7%-3.6%). CONCLUSION: A high prevalence of antibodies against SARS-CoV-2 was found in Kosovo before the start of the vaccination campaign. However, the results of the survey suggested that, by the end of June 2021, a desirable level of protection from the SARS-CoV-2 virus had not been reached.