RESUMEN
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
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
BACKGROUND: Nasopharyngeal carcinoma (NPC) is diagnosed relatively late and has a poor prognosis, requiring early detection to reduce the disease burden. This diagnostic test accuracy meta-analysis evaluated the serological diagnostic value of nine EBV-related IgA antibody panels (EBNA1-IgA, VCA-IgA, EA-IgA, Zta-IgA, EBNA1-IgA + VCA-IgA, VCA-IgA + EA-IgA, VCA-IgA + Rta-IgG, EBNA1-IgA + VCA-IgA + Zta-IgA and VCA-IgA + EA-IgA + Rta-IgG), aiming to identify suitable serological detection biomarkers for NPC screening. METHODS: PubMed, Embase, China National Knowledge Infrastructure and Chinese BioMedical Literature Database were searched from January 1st, 2000 to September 30th, 2023, with keywords nasopharyngeal carcinoma, IgA, screening, early detection, early diagnosis, sensitivity and specificity. Articles on the diagnostic value of serum EBV-related IgA antibody panels for NPC were included. Study selection, data extraction, and quality assessment were performed independently by two researchers, and a third researcher was consulted in the case of disagreement. Bivariate models were used for statistical analysis. The quality of included studies was evaluated through Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). RESULTS: A total of 70 articles were included, involving 11 863 NPC cases and 34 995 controls. Among the nine EBV-related IgA antibody panels, EBNA1-IgA + VCA-IgA [0.928 (0.898, 0.950)], VCA-IgA + Rta-IgG [0.925 (0.890, 0.949)], EBNA1-IgA + VCA-IgA + Zta-IgA [0.962 (0.909, 0.985)] and VCA-IgA + EA-IgA + Rta-IgG [0.945 (0.918, 0.964)] demonstrated higher pooled sensitivity (95%CI). In terms of diagnostic odds ratio (DOR) (95%CI), EBNA1-IgA + VCA-IgA [107.647 (61.173, 189.430)], VCA-IgA + Rta-IgG [105.988 (60.118, 186.857)] and EBNA1-IgA + VCA-IgA + Zta-IgA [344.450 (136.351, 870.153)] showed superior performance. Additionally, the SROC curves for EBNA1-IgA + VCA-IgA and VCA-IgA + Rta-IgG were more favorable. However, publication bias was detected for VCA-IgA (P = 0.005) and EBNA1-IgA + VCA-IgA (P = 0.042). CONCLUSIONS: In general, parallel detection of serum EBNA1-IgA, VCA-IgA and Zta-IgA antibodies using ELISA demonstrates better pooled sensitivity and DOR among the studied panels. In the cases where fewer indicators are used, serum VCA-IgA and EBNA1-IgA/Rta-IgG antibody panel exhibits a comparable performance. TRIAL REGISTRATION: The International Prospective Register of Systematic Reviews registration number: CRD42023426984, registered on May 28, 2023.
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Anticuerpos Antivirales , Infecciones por Virus de Epstein-Barr , Inmunoglobulina A , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/inmunología , Detección Precoz del Cáncer/métodos , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/sangre , Antígenos Nucleares del Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/inmunología , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/inmunología , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/sangre , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/virología , Sensibilidad y Especificidad , Pruebas Serológicas/métodosAsunto(s)
Vasculitis por IgA , Síndrome Nefrótico , Humanos , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/inmunología , Síndrome Nefrótico/tratamiento farmacológico , Vasculitis por IgA/diagnóstico , Vasculitis por IgA/tratamiento farmacológico , Vasculitis por IgA/complicaciones , Vasculitis por IgA/inmunología , Resultado del Tratamiento , Niño , Masculino , Femenino , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Inmunosupresores/uso terapéutico , BiopsiaRESUMEN
The American manatee (Trichechus manatus), experiencing population declines due to various threats, is the focus of conservation efforts that include the capture, rehabilitation, and release of orphaned calves when their mothers are unable to care for them. These efforts are compromised by the use of commercially available milk substitutes that lack essential components found in natural manatee breast milk, particularly immunoglobulin A (IgA). IgA plays a crucial role in nurturing the immune mucosal system and fostering a healthy microbiota. However, research on IgA in non-maternally fed manatees is limited due to the lack of species-specific reagents. To address this gap, our study employs immuno-informatics analysis to compare IgA sequences from manatees with those from other species, aiming to explore epitope similarity and sharing. We compared the protein sequence of manatee IgA with available IgA sequences, assessing similarity at the sequence, 3D structures, and epitope levels. Our findings reveal that human IgA exhibits the highest similarity in terms of sequence and 3D structure. Additionally, epitope analysis shows high conservation, identity, and similarity of predicted epitopes compared to human IgA. Future studies should focus on functional analysis using human IgA polyclonal reagents to detect manatee IgA in breast milk. Our findings highlight the potential of comparative analysis in advancing the understanding of immunology in non-human animals and overcoming challenges associated with the scarcity of species-specific reagents.
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Epítopos , Inmunoglobulina A , Animales , Humanos , Inmunoglobulina A/inmunología , Epítopos/inmunología , Biología Computacional/métodos , Secuencia de AminoácidosRESUMEN
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
BACKGROUND: The aim of this study is to investigate the impact of arginine on immune function and postoperative complications in colorectal cancer (CRC) patients. METHODS: We conducted a comprehensive search to identify eligible RCTs in various databases, such as PubMed, Cochrane Library, EMBASE, Web of Science, MEDLINE, China National Knowledge Infrastructure (CNKI), Wanfang, VIP Medicine Information System (VIP), and Chinese Biomedical Database (CBM). This study aimed to examine IgA, IgG, and IgM levels as well as CD4+ and CD8+ counts as well as the CD4+/CD8+ ratio. Anastomotic leaking, length of stay (LOS), and surgical site infection (SSI) were included as secondary outcomes. Stata (StataCorp, version 14.0) was utilized for data analysis. To ensure the results were reliable, we used meta-regression, sensitivity analysis, and publication bias analysis. RESULTS: A total of 24 publications (including 1883 patients) out of 681 that were retrieved fulfilled the inclusion criteria. The arginine group showed notable improvements in humoral immunity, with gains in IgA (SMD=0.45, 95% CI: 0.30-0.60), IgG (SMD=0.80, 95% CI: 0.64-0.96), and IgM (SMD=0.66, 95% CI: 0.39-0.93). With regards to cellular immunity, the arginine group exhibited a substantial increase in the CD4+ T cell count (SMD = 1.03, 95% CI: 0.67-1.38) compared to the control group. However, the CD4+/CD8+ ratio decreased significantly (SMD=1.37, 95% CI: 0.88-1.86) in the same arginine group, indicating a change in the balance between these two cell types. Additionally, the CD8+ T cell count showed a notable decrease (SMD=-0.70, 95% CI: -1.09 to -0.32) in the arginine group when compared to the control group. Anastomotic leakage was also considerably lower in the arginine group (SMD=-0.05, 95% CI: -0.08 to -0.02), the rate of SSIs was lower (RR = -0.02, 95% CI: -0.05-0), and the length of time patients spent in the hospital was shorter (SMD=-0.15, 95% CI: -0.38 to -0.08). CONCLUSIONS: After radiation treatment for CRC, arginine improves immune function and decreases the risk of infection problems. TRIAL REGISTRATION: Registration with PROSPERO for this meta-analysis is number CRD42024520509.
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Arginina , Neoplasias Colorrectales , Complicaciones Posoperatorias , Humanos , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/inmunología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/inmunología , Inmunoglobulina A/sangre , Tiempo de Internación/estadística & datos numéricos , Infección de la Herida Quirúrgica/inmunología , Relación CD4-CD8 , Inmunidad Humoral , Fuga Anastomótica/etiologíaRESUMEN
mRNA-based COVID-19 vaccines have played a critical role in reducing severe outcomes of COVID-19. Humoral immune responses against SARS-CoV-2 after vaccination have been extensively studied in blood; however, limited information is available on the presence and duration of SARS-CoV-2 specific antibodies in saliva and other mucosal fluids. Saliva offers a non-invasive sampling method that may also provide a better understanding of mucosal immunity at sites where the virus enters the body. Our objective was to evaluate the salivary immune response after vaccination with the COVID-19 Moderna mRNA-1273 vaccine. Two hundred three staff members of the U.S. Centers for Disease Control and Prevention were enrolled prior to receiving their first dose of the mRNA-1273 vaccine. Participants were asked to self-collect 6 saliva specimens at days 0 (prior to first dose), 14, 28 (prior to second dose), 42, and 56 using a SalivaBio saliva collection device. Saliva specimens were tested for anti-spike protein SARS-CoV-2 specific IgA and IgG enzyme immunoassays. Overall, SARS-CoV-2-specific salivary IgA titers peaked 2 weeks after each vaccine dose, followed by a sharp decrease during the following weeks. In contrast to IgA titers, IgG antibody titers increased substantially 2 weeks after the first vaccine dose, peaked 2 weeks after the second dose and persisted at an elevated level until at least 8 weeks after the first vaccine dose. Additionally, no significant differences in IgA/IgG titers were observed based on age, sex, or race/ethnicity. All participants mounted salivary IgA and IgG immune responses against SARS-CoV-2 after receiving the mRNA-1273 COVID-19 vaccine. Because of the limited follow-up time for this study, more data are needed to assess the antibody levels beyond 2 months after the first dose. Our results confirm the potential utility of saliva in assessing immune responses elicited by immunization and possibly by infection.
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Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunoglobulina A , Inmunoglobulina G , SARS-CoV-2 , Saliva , Vacunación , Humanos , Saliva/inmunología , Femenino , Masculino , Adulto , SARS-CoV-2/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Persona de Mediana Edad , Inmunoglobulina A/inmunología , Inmunoglobulina A/análisis , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangre , Vacuna nCoV-2019 mRNA-1273 , Adulto Joven , Inmunidad Mucosa/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and obstetric morbidity, with accurate laboratory examination of antiphospholipid antibodies (aPLs) being crucial for diagnosis. This study focused on anti-ß2 glycoprotein I (aß2GPI) antibodies and aimed to establish the first population-based cutoff values for aß2GPI IgA/IgM/IgG antibodies in non-pregnant women of reproductive age in Southwest China. The study cohort comprised 181 healthy women of reproductive age for study. Blood samples were collected on an early morning fast. Anti-ß2GPI antibodies including IgA, IgM and IgG were measured in serum using the HOB® BioCLIA kit. According to the Clinical and Laboratory Standards Institute (CLSI) guidelines, the study used non-parametric percentile methods to calculate the 95th, 97.5th, and 99th percentiles cutoff values for aß2GPI IgA/IgM/IgG antibodies, along with corresponding 90% confidence intervals (CI), while excluding outliers. A total of 168 independent samples were collected for verification, including 85 samples from healthy subjects and 83 samples from APS patients, in order to evaluate the analytical performance of the obtained cutoff values. The 99th percentile cutoff values were 3.36 RU/mL for aß2GPI IgA, 27.54 RU/mL for aß2GPI IgM and 1.81 RU/mL for aß2GPI IgG, which indicated that the levels of aß2GPI IgM antibodies were generally higher compared to those of IgA and IgG antibodies. Our established reference range was confirmed to be successful in validating the detected values of aß2GPI antibodies in all healthy controls. With the 99th percentile cutoff value, the sensitivity was 14.46% for aß2GPI IgA, 22.89% for aß2GPI IgG, and 9.64% for aß2GPI IgM in APS patients. This study established population-based cutoff values that are applicable to the local population for the accurate laboratory examination of aß2GPI antibodies in non-pregnant women of reproductive age. The study also recommends paying more attention to IgM positivity in women of reproductive age.
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Síndrome Antifosfolípido , Inmunoglobulina G , Inmunoglobulina M , beta 2 Glicoproteína I , Humanos , Femenino , beta 2 Glicoproteína I/inmunología , Adulto , China , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/diagnóstico , Inmunoglobulina M/sangre , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina A/sangre , Persona de Mediana Edad , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Adulto Joven , Valores de Referencia , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , AdolescenteRESUMEN
Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in transient antibody response against the spike protein. The individual immune status at the time of vaccination influences the response. Using mathematical models of antibody decay, we determined the dynamics of serum immunoglobulin G (IgG) and serum immunoglobulin A (IgA) over time. Data fitting to longitudinal IgG and IgA titers was used to quantify differences in antibody magnitude and antibody duration among infection-naïve and infection-positive vaccinees. We found that prior infections result in more durable serum IgG and serum IgA responses, with prior symptomatic infections resulting in the most durable serum IgG response and prior asymptomatic infections resulting in the most durable serum IgA response. These findings can guide vaccine boosting schedules.
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Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunoglobulina A , Inmunoglobulina G , SARS-CoV-2 , Humanos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/prevención & control , SARS-CoV-2/inmunología , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunación , Glicoproteína de la Espiga del Coronavirus/inmunología , Modelos InmunológicosRESUMEN
SpikoGen® vaccine is a subunit COVID-19 vaccine composed of an insect cell expressed recombinant spike protein extracellular domain formulated with Advax-CpG55.2™ adjuvant. A randomized double-blind, placebo-controlled Phase II clinical trial was conducted in 400 adult subjects who were randomized 3:1 to receive two intramuscular doses three weeks apart of either SpikoGen® vaccine 25 µg or saline placebo, as previously reported. This study reports a post hoc analysis of the trial data to explore potential immune correlates of SpikoGen® vaccine protection. A range of humoral markers collected pre- and post-vaccination, including spike- and RBD-binding IgG and IgA, surrogate (sVNT), and conventional (cVNT) virus neutralization tests were compared between participants who remained infection-free or got infected over three months of follow-up. From 2 weeks after the second vaccine dose, 21 participants were diagnosed with SARS-CoV-2 infection, 13 (4.2%) in the SpikoGen® group and 8 (9%) in the placebo group. Those in the vaccinated group who experienced breakthrough infections had significantly lower sVNT titers (GMT 5.75 µg/mL, 95% CI; 3.72-8.91) two weeks after the second dose (day 35) than those who did not get infected (GMT 21.06 µg/mL, 95% CI; 16.57-26.76). Conversely, those who did not develop SARS-CoV-2 infection during follow-up had significantly higher baseline sVNT, cVNT, spike-binding IgG and IgA, and RBD-binding IgG, consistent with a past SARS-CoV-2 infection. SpikoGen® further reduced the risk of re-infection (OR 0.29) in baseline seropositive (previously infected) as well as baseline seronegative participants. This indicates that while SpikoGen vaccine is protective in seronegative individuals, those with hybrid immunity have the most robust protection.
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Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/virología , SARS-CoV-2/inmunología , Femenino , Masculino , Adulto , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Persona de Mediana Edad , Método Doble Ciego , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina A/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Adyuvantes de Vacunas , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , AncianoRESUMEN
INTRODUCTION: Malnutrition in children is epidemic in developing countries. Several health issues and consequences are believed to develop due to this phenomenon. Children's oral health is also affected by malnutrition. The main aspects of oral health status are caries experience, the existence of cariogenic bacteria, and salivary immunoglobulin A.
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Caries Dental , Salud Bucal , Saliva , Humanos , Caries Dental/epidemiología , Niño , Saliva/inmunología , Masculino , Femenino , Desnutrición/epidemiología , Inmunoglobulina A Secretora/metabolismo , Inmunoglobulina A/metabolismoRESUMEN
IgA antibodies play an important role in mucosal immunity. However, there is still no effective way to consistently boost mucosal IgA responses, and the factors influencing these responses are not fully understood. We observed that colonization with the murine intestinal symbiotic protozoan Tritrichomonas musculis (T.mu) boosted antigen-specific mucosal IgA responses in wild-type C57BL/6 mice. This enhancement was attributed to the accumulation of free arachidonic acid (ARA) in the intestinal lumen, which served as a signal to stimulate the production of antigen-specific mucosal IgA. When ARA was prevented from undergoing its downstream metabolic transformation using the 5-lipoxygenase inhibitor zileuton or by blocking its downstream biological signaling through genetic deletion of the Leukotriene B4 receptor 1 (Blt1), the T.mu-mediated enhancement of antigen-specific mucosal IgA production was suppressed. Moreover, both T.mu transfer and dietary supplementation of ARA augmented the efficacy of an oral vaccine against Salmonella infection, with this effect being dependent on Blt1. Our findings elucidate a tripartite circuit linking nutrients from the diet or intestinal microbiota, host lipid metabolism, and the mucosal humoral immune response.
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Inmunidad Mucosa , Inmunoglobulina A , Metabolismo de los Lípidos , Ratones Endogámicos C57BL , Receptores de Leucotrieno B4 , Transducción de Señal , Animales , Metabolismo de los Lípidos/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina A/metabolismo , Transducción de Señal/inmunología , Ratones , Receptores de Leucotrieno B4/metabolismo , Receptores de Leucotrieno B4/inmunología , Ácido Araquidónico/metabolismo , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Femenino , Microbioma Gastrointestinal/inmunología , Ratones NoqueadosRESUMEN
BACKGROUND: The immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and immunisation is variable. OBJECTIVES: To describe the humoral immune response by correlating IgA and IgG antibodies with NAbs titration following CoronaVac® immunisation and an mRNA (Comirnaty®) booster among healthcare workers (HCWs) and to compare the cytokine and interleukin profiles between HCWs vaccinated with CoronaVac and coronavirus disease 2019 (COVID-19) infected patients. METHODS: Samples from 133 HCWs collected at 20 (T1) and 90 (T2) days after CoronaVac immunisation and 15 (T3) days after a booster dose with the Comirnaty vaccine were analysed for IgA and IgG EIA and neutralisation assay. Cytokine levels from vaccinated individuals at T1 day and COVID-19 patients were compared. FINDINGS: Neutralising antibodies (NAbs) were observed in 81.7% of participants at T1, but only 49.2% maintained detectable NAbs after 90 days. The booster dose increased NAbs response in all participants. The cytokines with the highest levels post-vaccination were IL-6 and MCP-1. The MCP-1, IL-18, and IFN- γ levels were higher in COVID-19 patients than in vaccinated HCWs, while IL-22 levels increased in the vaccinated HCWs group. MAIN CONCLUSIONS: The neutralisation titres in the T2 samples decreased, and antibody levels detected at T2 showed a more significant reduction than the neutralisation. The higher IL-22 expression in immunised individuals compared to those with COVID-19 suggests that IL-22 may be beneficial in protecting against severe disease.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Citocinas , Personal de Salud , Inmunización Secundaria , Inmunoglobulina G , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/prevención & control , Masculino , Femenino , Anticuerpos Antivirales/sangre , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Persona de Mediana Edad , Citocinas/inmunología , Citocinas/sangre , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Inmunoglobulina A/análisis , Vacunación , Adulto Joven , Inmunidad Humoral/inmunología , Vacunas de Productos InactivadosRESUMEN
Immunoglobulin A (IgA) is a major gut antibody that coats commensal gut bacteria and contributes to shaping a stable gut bacterial composition. Although previous studies have shown that cyclic oligosaccharides, including cyclic nigerosyl-1,6-nigerose (CNN) and cyclodextrins (CDs, including αCD, ßCD, and γCD), alter the gut bacterial composition, it remains unclear whether cyclic oligosaccharides modify the IgA coating of gut bacteria, which relates to cyclic oligosaccharide-induced alteration of the gut bacterial composition. To address this issue, mice were maintained for 12 weeks on diets containing CNN, αCD, ßCD, or γCD; the animals' feces were evaluated for their bacterial composition and the IgA coating index (ICI), a measure of the degree of IgA coating of bacteria. We observed that the intake of each cyclic oligosaccharide altered the gut bacterial composition, with changes in the ICI found at both the phylum and genus levels. The ICI for Bacillota, Lachnospiraceae NK4A136 group, UC Lachnospiraceae, and Tuzzerella were significantly and positively correlated with the relative abundance (RA) in total bacteria for these bacteria; in contrast, significant correlations were not seen for other phyla and genera. Our observations suggest that cyclic oligosaccharide-induced modulation of the IgA coating of gut bacteria may partly relate to changes in the community structure of the gut bacteria.
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Heces , Microbioma Gastrointestinal , Inmunoglobulina A , Oligosacáridos , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Oligosacáridos/farmacología , Ratones , Heces/microbiología , Bacterias/efectos de los fármacos , Masculino , Ciclodextrinas/farmacología , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Sunitinib, a multi-targeted tyrosine kinase inhibitor, is used as a second-line therapy for gastrointestinal stromal tumors (GIST) resistant to imatinib. However, its impact on the vascular endothelial growth factor (VEGF) pathway can lead to significant toxicities, including hypertension and thrombotic microangiopathy (TMA). CASE PRESENTATION: This case report describes a unique instance of a patient with metastatic GIST who developed endocapillary proliferative glomerulonephritis (EPGN) with IgA2 deposits and TMA following sunitinib treatment. The patient presented with severe hypertension, nephrotic syndrome, and acute kidney injury. Renal biopsy confirmed the diagnosis, revealing IgA2 deposits, which are not commonly associated with TMA. Discontinuation of sunitinib led to a rapid improvement in renal function and proteinuria. The potential mechanisms underlying sunitinib-induced glomerular injury may involve the blockade of VEGFR-1, affecting immune cell recruitment and function, and the disruption of the nitric oxide and endothelin systems, leading to endothelial damage and immune dysregulation. Management of these toxicities requires a personalized approach, with options ranging from symptomatic relief to drug discontinuation. The use of endothelin receptor antagonists and other therapeutic alternatives for GIST management is discussed. CONCLUSIONS: This case highlights the complex interplay between the therapeutic effects of sunitinib and its potential renal and cardiovascular toxicities, emphasizing the need for close monitoring and effective management strategies to optimize patient outcomes.
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Antineoplásicos , Tumores del Estroma Gastrointestinal , Sunitinib , Microangiopatías Trombóticas , Humanos , Sunitinib/uso terapéutico , Sunitinib/efectos adversos , Microangiopatías Trombóticas/inducido químicamente , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Masculino , Inmunoglobulina A/metabolismo , Glomerulonefritis por IGA/patología , Glomerulonefritis Membranoproliferativa/inducido químicamente , Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Persona de Mediana Edad , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/patologíaRESUMEN
A 73-year-old man with lung squamous cell carcinoma was administered carboplatin + nab-paclitaxel + pembrolizumab for four cycles. Subsequently, he presented with multiple purpuras on his extremities, joint swelling on his fingers, abdominal pain, and diarrhea, accompanied by acute kidney injury (AKI), increased proteinuria, hematuria, and elevated C-reactive protein levels. Skin biopsy showed leukocytoclastic vasculitis as well as IgA and C3 deposition in the vessel walls. Based on these findings, the patient was diagnosed with IgA vasculitis as an immune-related adverse event (irAE) induced by carboplatin + nab-paclitaxel + pembrolizumab. After discontinuation of pembrolizumab and glucocorticoids, the symptoms immediately resolved. Regular monitoring of skin, blood tests, and urinalysis are necessary, and the possibility of irAE IgA vasculitis should be considered in cases of purpura and AKI during treatment with immune checkpoint inhibitors.
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Albúminas , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatino , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Paclitaxel , Humanos , Masculino , Anciano , Carboplatino/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , Paclitaxel/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Albúminas/efectos adversos , Albúminas/administración & dosificación , Vasculitis por IgA/inducido químicamente , Vasculitis por IgA/diagnóstico , Inmunoglobulina A , Inhibidores de Puntos de Control Inmunológico/efectos adversosRESUMEN
The IgG response against SARS-CoV-2 infection can persist for over six months (long response; LR). However, among 30% of those infected, the duration can be as short as three months or less (short response; SR). The present study assembled serological data on the anti-SARS-CoV-2 IgG response duration of two previous studies and integrated these results with the plasmatic cytokine levels and genetic profile of 10 immune-relevant SNPs that were also previously published, along with the plasmatic total IgG, IgA, and IgM levels, allowing for the genetic, clinical, immunological, and epidemiological aspects of the post-COVID-19 IgG response duration to be understood. The SR was associated with previous mild acute COVID-19 and with an SNP (rs2228145) in IL6R related to low gene expression. Additionally, among the SR subgroup, no statistically significant Spearman correlations were observed between the plasma levels of IL-17A and the Th17 regulatory cytokines IFN-γ (rs = 0.2399; p = 0.1043), IL-4 (rs = 0.0273; p = 0.8554), and IL-2 (rs = 0.2204; p = 0.1365), while among the LR subgroup, weaker but statistically significant Spearman correlations were observed between the plasma levels of IL-17A and IFN-γ (rs = 0.3873; p = 0.0016), IL-4 (rs = 0.2671; p = 0.0328), and IL-2 (rs = 0.3959; p = 0.0012). These results suggest that the Th17 response mediated by the IL-6 pathway has a role in the prolonged IgG response to SARS-CoV-2 infection.
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Anticuerpos Antivirales , COVID-19 , Inmunoglobulina G , Polimorfismo de Nucleótido Simple , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/epidemiología , COVID-19/sangre , COVID-19/virología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Masculino , Femenino , Receptores de Interleucina-6/genética , Persona de Mediana Edad , Adulto , Interleucina-17/sangre , Interleucina-17/genética , Citocinas/sangre , Inmunoglobulina A/sangre , Interferón gamma/sangre , Interferón gamma/genética , Inmunoglobulina M/sangre , Interleucina-4/sangre , Interleucina-4/genética , AncianoRESUMEN
Entamoeba histolytica, the causative agent of amebiasis, is one of the top three parasitic causes of mortality worldwide. However, no vaccine exists against amebiasis. Using a lead candidate vaccine containing the LecA fragment of Gal-lectin and GLA-3M-052 liposome adjuvant, we immunized rhesus macaques via intranasal or intramuscular routes. The vaccine elicited high-avidity functional humoral responses as seen by the inhibition of amebic attachment to mammalian target cells by plasma and stool antibodies. Importantly, antigen-specific IFN-γ-secreting peripheral blood mononuclear cells (PBMCs) and IgG/IgA memory B cells (BMEM) were detected in immunized animals. Furthermore, antigen-specific antibody and cellular responses were maintained for at least 8 months after the final immunization as observed by robust LecA-specific BMEM as well as IFN-γ+ PBMC responses. Overall, both intranasal and intramuscular immunizations elicited a durable and functional response in systemic and mucosal compartments, which supports advancing the LecA+GLA-3M-052 liposome vaccine candidate to clinical testing.
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Administración Intranasal , Anticuerpos Antiprotozoarios , Entamoeba histolytica , Entamebiasis , Interferón gamma , Leucocitos Mononucleares , Liposomas , Macaca mulatta , Vacunas Antiprotozoos , Animales , Entamoeba histolytica/inmunología , Liposomas/inmunología , Liposomas/administración & dosificación , Vacunas Antiprotozoos/inmunología , Vacunas Antiprotozoos/administración & dosificación , Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antiprotozoarios/inmunología , Leucocitos Mononucleares/inmunología , Entamebiasis/prevención & control , Entamebiasis/inmunología , Interferón gamma/inmunología , Interferón gamma/metabolismo , Inyecciones Intramusculares , Inmunogenicidad Vacunal , Adyuvantes de Vacunas/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Linfocitos B/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina A/sangre , Antígenos de Protozoos/inmunología , Inmunidad Humoral , Memoria Inmunológica , Proteínas Protozoarias/inmunologíaRESUMEN
Introduction: Galactose-deficient IgA1 (GdIgA1) is critical in the formation of immunodeposits in IgA nephropathy (IgAN), whereas the origin of GdIgA1 is unknown. We focused on the immune response to fecal microbiota in patients with IgAN. Methods: By running 16S ribosomal RNA gene sequencing, we compared IgAN samples to the control samples from household-matched or non-related individuals. Levels of plasma GdIgA1 and poly-IgA complexes were measured, and candidate microbes that can either incite IgA-directed antibody response or degrade IgA through specific IgA protease activities were identified. Results: The IgAN group showed a distinct composition of fecal microbiota as compared to healthy controls. Particularly, high abundance of Escherichia-Shigella was associated with the disease group based on analyses using receiver operating characteristic (area under curve, 0.837; 95% CI, 0.738-0.914), principle coordinates, and the linear discriminant analysis effect size algorithm (linear discriminant analysis score, 4.56; p < 0.001). Accordingly, the bacterial levels directly correlated with high titers of plasma GdIgA1(r = 0.36, p < 0.001), and patients had higher IgA1 against stx2(2.88 ± 0.46 IU/mL vs. 1.34 ± 0.35 IU/mL, p = 0.03), the main antigen of Escherichia-Shigella. Conversely, the healthy controls showed relatively higher abundance of the commensal bacteria that produce IgA-degrading proteases. Particularly, the abundance of some intestinal bacteria expressing IgA proteases showed an inverse correlation with the levels of plasma GdIgA1 in IgAN. Conclusion: Our data suggest that mucosal IgA production, including those of GdIgA1, is potentially linked to the humoral response to gut Escherichia-Shigella as one of the sources of plasma GdIgA1. Conversely, the IgA protease-producing microbiota in the gut are suppressed in patients with IgAN.