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1.
Sci Immunol ; 9(94): eadk0092, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38579014

RESUMEN

The transition from immunoglobulin M (IgM) to affinity-matured IgG antibodies is vital for effective humoral immunity. This is facilitated by germinal centers (GCs) through affinity maturation and preferential maintenance of IgG+ B cells over IgM+ B cells. However, it is not known whether the positive selection of the different Ig isotypes within GCs is dependent on specific transcriptional mechanisms. Here, we explored IgG1+ GC B cell transcription factor dependency using a CRISPR-Cas9 screen and conditional mouse genetics. We found that MIZ1 was specifically required for IgG1+ GC B cell survival during positive selection, whereas IgM+ GC B cells were largely independent. Mechanistically, MIZ1 induced TMBIM4, an ancestral anti-apoptotic protein that regulated inositol trisphosphate receptor (IP3R)-mediated calcium (Ca2+) mobilization downstream of B cell receptor (BCR) signaling in IgG1+ B cells. The MIZ1-TMBIM4 axis prevented mitochondrial dysfunction-induced IgG1+ GC cell death caused by excessive Ca2+ accumulation. This study uncovers a unique Ig isotype-specific dependency on a hitherto unidentified mechanism in GC-positive selection.


Asunto(s)
Linfocitos B , Inmunoglobulina G , Ratones , Animales , Inmunoglobulina G/metabolismo , Centro Germinal , Inmunoglobulina M/metabolismo , Transducción de Señal
2.
Eur J Med Res ; 29(1): 223, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38581072

RESUMEN

BACKGROUND: COVID-19 pneumonia causes hyperinflammatory response that culminates in acute respiratory syndrome (ARDS) related to increased multiorgan dysfunction and mortality risk. Antiviral-neutralizing immunoglobulins production reflect the host humoral status and illness severity, and thus, immunoglobulin (Ig) circulating levels could be evidence of COVID-19 prognosis. METHODS: The relationship among circulating immunoglobulins (IgA, IgG, IgM) and COVID-19 pneumonia was evaluated using clinical information and blood samples in a COVID-19 cohort composed by 320 individuals recruited during the acute phase and followed up to 4 to 8 weeks (n = 252) from the Spanish first to fourth waves. RESULTS: COVID-19 pneumonia development depended on baseline Ig concentrations. Circulating IgA levels together with clinical features at acute phase was highly associated with COVID-19 pneumonia development. IgM was positively correlated with obesity (ρb = 0.156, P = 0.020), dyslipemia (ρb = 0.140, P = 0.029), COPD (ρb = 0.133, P = 0.037), cancer (ρb = 0.173, P = 0.007) and hypertension (ρb = 0.148, P = 0.020). Ig concentrations at recovery phase were related to COVID-19 treatments. CONCLUSIONS: Our results provide valuable information on the dynamics of immunoglobulins upon SARS-CoV-2 infection or other similar viruses.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Inmunoglobulina G , Inmunoglobulina M , Anticuerpos Antivirales , Inmunoglobulina A
3.
J Med Virol ; 96(4): e29583, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38576266

RESUMEN

The measles virus, also known as the morbillivirus, or MV, is a virus that infects humans. The goal of this research is to assess to adult cases of measles. Eleven patients thought to be confirmed cases of measles were enrolled in the investigation. Following the identification of symptoms of tiredness, fever, and rash in one soldier, the results of 10 more troops from the pertinent military group were assessed. The diagnosis was made based on the presence of serum immunoglobulin M (IgM) and positive polymerase chain reaction (PCR) results. When the control IgM, immunoglobulin G, and PCR findings were evaluated a fortnight after hospitalization, a cluster of 11 incidents was found. It is now necessary to address the issue of the cautious stance towards vaccination or the anti-vaccination sentiment that has grown increasingly popular, particularly in light of the COVID-19 pandemic, for both our nation and the entire world.


Asunto(s)
Sarampión , Pandemias , Adulto , Humanos , Lactante , Anticuerpos Antivirales , Sarampión/diagnóstico , Sarampión/epidemiología , Sarampión/prevención & control , Virus del Sarampión/genética , Brotes de Enfermedades , Hospitalización , Hospitales , Inmunoglobulina M , Vacuna Antisarampión
4.
Zhonghua Bing Li Xue Za Zhi ; 53(4): 377-383, 2024 Apr 08.
Artículo en Chino | MEDLINE | ID: mdl-38556822

RESUMEN

Objective: To study the clinicopathological features of Sjogren's syndrome (SS) with liver injury and to improve the understanding of this disease. Methods: Forty-nine patients with SS complicated with liver injury were collected from Beijing Ditan Hospital, Capital Medical University from October 2008 to January 2022. All patients underwent ultrasound-guided liver biopsy, and all specimens were stained with HE. The histopathologic characteristics were observed and the pathologic indexes were graded. Immunohistochemical stains for CK7, CK19, CD38, MUM1 and CD10 were performed by EnVision method; and special histochemical stains for reticulin, Masson's trichrome, Rhodanine, Prussian blue, periodic acid Schiff (PAS) and D-PAS stains were conducted. Results: The age of patients ranged from 31 to 66 years, including 3 males and 46 females. SS combined with drug-induced liver injury was the most common (22 cases, 44.9%), followed by autoimmune liver disease (13 cases, 26.5%, including primary biliary cholangitis in eight cases, autoimmune hepatitis in 3 cases, and PBC-AIH overlap syndrome in 2 cases), non-alcoholic fatty liver disease (NAFLD, 9 cases, 18.4%) and other lesions (5 cases, 10.2%; including 3 cases of nonspecific liver inflammation, 1 case of liver amyloidosis, and 1 case of porto-sinusoidal vascular disease). Among them, 28 cases (57.1%) were associated with obvious interlobular bile duct injury, mainly in SS combined with PBC group and drug-induced liver injury group. Twenty-three cases (46.9%) were associated with hepatocyte steatosis of varying degrees. In SS with autoimmune liver disease group, ISHAK score, degree of fibrosis bile duct injury, bile duct remodeling, lymphocyte infiltration of portal area, and plasma cell infiltration, MUM1 and CD38 expression; serum ALP and GGT, IgM; elevated globulin; positive AMA, proportion of AMA-M2 positive and IgM positive were all significantly higher than those in other groups(all P<0.05). Serum ALT, direct bilirubin and SSA positive ratio in SS combined with drug liver group were significantly higher than those in other groups(all P<0.05). The serum total cholesterol level in SS combined with PBC group (P=0.006) and NALFD group (P=0.011) were significantly higher than those in other groups (P<0.05). Conclusions: The pathologic manifestations of SS patients with liver injury are varied. The inflammatory lesions of SS patients with autoimmune liver disease are the most serious, and the inflammatory lesions of SS patients with non-alcoholic fatty liver disease and non-specific inflammation are mild. Comprehensive analysis of liver histopathologic changes and laboratory findings is helpful for the diagnosis of SS complicated with different types of liver injury.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatitis Autoinmune , Cirrosis Hepática Biliar , Enfermedad del Hígado Graso no Alcohólico , Síndrome de Sjögren , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Síndrome de Sjögren/complicaciones , Cirrosis Hepática Biliar/complicaciones , Cirrosis Hepática Biliar/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Hígado , Hepatitis Autoinmune/complicaciones , Hepatitis Autoinmune/diagnóstico , Inflamación/complicaciones , Enfermedad Hepática Inducida por Sustancias y Drogas/complicaciones , Inmunoglobulina M
5.
J Med Virol ; 96(4): e29595, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38587217

RESUMEN

Systemic autoimmune diseases (SADs) are a growing spectrum of autoimmune disorders that commonly affect multiple organs. The role of Epstein-Barr virus (EBV) infection or reactivation as a trigger for the initiation and progression of SADs has been established, while the relationship between EBV envelope glycoproteins and SADs remains unclear. Here, we assessed the levels of IgG, IgA, and IgM against EBV glycoproteins (including gp350, gp42, gHgL, and gB) in serum samples obtained from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and found that RA and SLE patients exhibited a statistically significant increase in the levels of 8 and 11 glycoprotein antibodies, respectively, compared to healthy controls (p < 0.05). The LASSO model identified four factors as significant diagnostic markers for RA: gp350 IgG, gp350 IgA, gHgL IgM, and gp42 IgA; whereas for SLE it included gp350 IgG, gp350 IgA, gHgL IgA, and gp42 IgM. Combining these selected biomarkers yielded an area under the curve (AUC) of 0.749 for RA and 0.843 for SLE. We subsequently quantified the levels of autoantibodies associated with SADs in mouse sera following immunization with gp350. Remarkably, none of the tested autoantibody levels exhibited statistically significant alterations. Elevation of glycoprotein antibody concentration suggests that Epstein-Barr virus reactivation and replication occurred in SADs patients, potentially serving as a promising biomarker for diagnosing SADs. Moreover, the absence of cross-reactivity between gp350 antibodies and SADs-associated autoantigens indicates the safety profile of a vaccine based on gp350 antigen.


Asunto(s)
Artritis Reumatoide , Enfermedades Autoinmunes , Infecciones por Virus de Epstein-Barr , Lupus Eritematoso Sistémico , Humanos , Animales , Ratones , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Anticuerpos Antivirales , Artritis Reumatoide/complicaciones , Glicoproteínas , Enfermedades Autoinmunes/complicaciones , Inmunoglobulina G , Inmunoglobulina A , Inmunoglobulina M
6.
Euro Surveill ; 29(14)2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38577804

RESUMEN

In February 2023, German public health authorities reported two dengue cases (one confirmed, one probable) and four possible cases who travelled to Ibiza, Spain, in late summer/autumn 2022; the infection was probably acquired through mosquito bites. Case 1 visited Ibiza over 1 week in late August with two familial companions; all three developed symptoms the day after returning home. Only Case 1 was tested; dengue virus (DENV) infection was confirmed by presence of NS1 antigen and IgM antibodies. Case 2 travelled to Ibiza with two familial companions for 1 week in early October, and stayed in the same town as Case 1. Case 2 showed symptoms on the day of return, and the familial companions 1 day before and 3 days after return; Case 2 tested positive for DENV IgM. The most probable source case had symptom onset in mid-August, and travelled to a dengue-endemic country prior to a stay in the same municipality of Ibiza for 20 days, until the end of August. Dengue diagnosis was probable based on positive DENV IgM. Aedes albopictus, a competent vector for dengue, has been present in Ibiza since 2014. This is the first report of a local dengue transmission event on Ibiza.


Asunto(s)
Aedes , Virus del Dengue , Dengue , Animales , Humanos , Dengue/diagnóstico , Dengue/epidemiología , Virus del Dengue/genética , España/epidemiología , Mosquitos Vectores , Brotes de Enfermedades , Inmunoglobulina M
7.
J Cell Mol Med ; 28(8): e18291, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38597412

RESUMEN

Natural immunoglobulin M (IgM) antibodies have been shown to recognize post-ischemic neoepitopes following reperfusion of tissues and to activate complement. Specifically, IgM antibodies and complement have been shown to drive hepatic ischemia reperfusion injury (IRI). Herein, we investigate the therapeutic effect of C2 scFv (single-chain antibody construct with specificity of a natural IgM antibody) on hepatic IRI in C57BL/6 mice. Compared with PBS-treated mice, C2 scFv-treated mice displayed almost no necrotic areas, significant reduction in serum ALT, AST and LDH levels, and significantly reduced in the number of TUNEL positive cells. Moreover, C2 scFv-treated mice exhibited a notable reduction in inflammatory cells after hepatic IRI than PBS-treated mice. The serum IL-6, IL-1ß, TNF-α and MPC-1 levels were also severely suppressed by C2 scFv. Interestingly, C2 scFv reconstituted hepatic inflammation and IRI in Rag1-/- mice. We found that C2 scFv promoted hepatic cell death and increased inflammatory cytokines and infiltration of inflammatory cells after hepatic IRI in Rag1-/- mice. In addition, IgM and complement 3d (C3d) were deposited in WT mice and in Rag1-/- mice reconstituted with C2 scFv, indicating that C2 scFv can affect IgM binding and complement activation and reconstitute hepatic IRI. C3d expression was significantly lower in C57BL/6 mice treated with C2 scFv compared to PBS, indicating that excessive exogenous C2 scFv inhibited complement activation. These data suggest that C2 scFv alleviates hepatic IRI by blocking complement activation, and treatment with C2 scFv may be a promising therapy for hepatic IRI.


Asunto(s)
Hígado , Daño por Reperfusión , Animales , Ratones , Ratones Endogámicos C57BL , Hígado/metabolismo , Inmunoglobulina M , Proteínas del Sistema Complemento , Proteínas de Homeodominio/metabolismo
8.
Front Immunol ; 15: 1354786, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38596680

RESUMEN

Introduction: With the reopening of schools during the coronavirus disease 2019 (COVID-19) pandemic, it was imperative to understand the role of students and education professionals in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, we determined the seroprevalence of the SARS-CoV-2 anti-nucleocapsid antibodies in the school community in Campo Grande, the capital and most populous city of the state of Mato Grosso do Sul (Brazil) and evaluated its association with sex, school level, and school type. Materials and methods: The survey was carried out in 20 public and private schools in the urban region of Campo Grande using the TR DPP® COVID-19 immunoglobulin M/immunoglobulin G (IgM/IgG) kit from the Immunobiological Technology Institute (Bio-Manguinhos, Rio de Janeiro, Brazil). Testing was carried out in three periods: from October to December 2021; from March to July 2022; and from August to November 2022. The participants were students aged 6-17 years enrolled in primary or secondary schools and professionals of different ages and roles. Results: During the first testing period, 162 participants were seropositive for the IgM and/or IgG anti-nucleocapsid SARS-CoV-2 antibodies, with an estimated seroprevalence of 19.6% using Bayesian multilevel regression. In the second period, 251 participants were seropositive (estimated seroprevalence, 34.6%), while in the third period, 393 participants were seroconverted (estimated seroprevalence, 56.7%). In 2022, there was an increase in the seroconversion rate compared to that in 2021. The most frequently described acute manifestations in the three periods were fever, headache, sore throat, and runny nose. In terms of the demographic profile, there was no predominance of seropositivity between the sexes, although women represented approximately 70% of the study population. There were also no differences between students and school staff. Discussion: The results made it possible to evaluate the extent of SARS-CoV-2 transmission in the school community through immunity developed against the virus, in addition to providing information about COVID-19 symptoms in children, adolescents, and adults.


Asunto(s)
COVID-19 , SARS-CoV-2 , Adolescente , Adulto , Niño , Humanos , Femenino , Brasil/epidemiología , COVID-19/epidemiología , Teorema de Bayes , Estudios Seroepidemiológicos , Anticuerpos Antivirales , Inmunoglobulina G , Inmunoglobulina M
9.
J Exp Med ; 221(5)2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38512136

RESUMEN

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.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Linfoma de Células B Grandes Difuso , Animales , Ratones , Linfocitos B , Linfoma de Células B Grandes Difuso/genética , Receptores de Antígenos de Linfocitos B , Inmunoglobulina M
10.
Sci Rep ; 14(1): 6748, 2024 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-38514826

RESUMEN

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.


Asunto(s)
Glomerulonefritis , Glomeruloesclerosis Focal y Segmentaria , Adulto , Femenino , Humanos , Masculino , Biopsia , Glomeruloesclerosis Focal y Segmentaria/epidemiología , Glomeruloesclerosis Focal y Segmentaria/patología , Inmunoglobulina M , Proteinuria , Estudios Retrospectivos , Albúmina Sérica , Estudios Multicéntricos como Asunto , Persona de Mediana Edad
11.
World J Surg ; 48(4): 896-902, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38479797

RESUMEN

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a rare inflammatory disease of the breast with clinical features that are often confused with those of breast cancer leading to delayed diagnosis and treatment. This retrospective study aimed to evaluate the therapeutic effectiveness and cosmetic results of drainage surgery using ultrasound-guided vacuum-assisted excision (VAE) for the treatment of IGM at the abscess stage. METHODS: The time of recovery, cases of further surgical intervention, and cosmetic results were retrospectively collected and analyzed from patients who underwent drainage with VAE or conventional drainage between October 2017 and August 2021. RESULTS: A total of 65 patients diagnosed with IGM at the abscess stage who underwent drainage surgery with VAE or conventional drainage surgery were enrolled. Overall, 38 (58.5%) underwent conventional drainage surgery and 27 (41.5%) underwent drainage with VAE. We found that patients who underwent VAE recovered much faster than those who underwent traditional drainage surgery (30.1 vs. 48.0 days). Nine (33.3%) patients in the VAE group required further surgical intervention after drainage, whereas 33 (86.8%) patients in the control group underwent another surgery to resect residual lesions. Additionally, patients in the VAE group were more satisfied with the breast appearance, mainly due to less influence of the scars and better symmetry of their breasts. CONCLUSION: Compared with conventional drainage surgery, drainage surgery using VAE for IGM patients at the abscess stage improved therapeutic and cosmetic outcomes. Furthermore, postoperative management of IGM is crucial.


Asunto(s)
Neoplasias de la Mama , Mastitis Granulomatosa , Femenino , Humanos , Estudios Retrospectivos , Mastitis Granulomatosa/diagnóstico por imagen , Mastitis Granulomatosa/cirugía , Absceso/diagnóstico por imagen , Absceso/cirugía , Neoplasias de la Mama/patología , Ultrasonografía Intervencional/métodos , Inmunoglobulina M
12.
Microbiol Spectr ; 12(4): e0165323, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38483477

RESUMEN

Vector-borne infections may underlie some rheumatic diseases, particularly in people with joint effusions. This study aimed to compare serum and synovial fluid antibodies to B. burgdorferi and Bartonella spp. in patients with rheumatic diseases. This observational, cross-sectional study examined paired synovial fluid and serum specimens collected from 110 patients with joint effusion between October 2017 and January 2022. Testing for antibodies to B. burgdorferi (using CDC criteria) and Bartonella spp. via two indirect fluorescent antibody (IFA) assays was performed as part of routine patient care at the Institute for Specialized Medicine (San Diego, CA, USA). There were 30 participants (27%) with positive two-tier B. burgdorferi serology and 26 participants (24%) with IFA seroreactivity (≥1:256) to B. henselae and/or B. quintana. Both B. burgdorferi IgM and IgG were detected more frequently in synovial fluid than serum: 27% of patients were either IgM or IgG positive in synovial fluid, compared to 15.5% in serum (P = 0.048). Conversely, B. henselae and B. quintana antibodies were detected more frequently in serum than synovial fluid; overall only 2% of patients had positive IFA titers in synovial fluid, compared to 24% who had positive IFA titers in serum (P < 0.001). There were no significant associations between B. burgdorferi or Bartonella spp. seroreactivity with any of the clinical rheumatological diagnoses. This study provides preliminary support for the importance of synovial fluid antibody testing for documenting exposure to B. burgdorferi but not for documenting exposure to Bartonella spp. IMPORTANCE: This study focuses on diagnostic testing for two common vector-borne diseases in an affected patient population. In it, we provide data showing that antibodies to B. burgdorferi, but not Bartonella spp., are more commonly found in synovial fluid than serum of patients with joint effusion. Since Lyme arthritis is a common-and sometimes difficult to diagnose-rheumatic disease, improving diagnostic capabilities is of utmost importance. While our findings are certainly not definitive for changes to practice, they do suggest that synovial fluid could be a useful sample for the clinical diagnosis of Lyme disease, and future prospective studies evaluating this claim are warranted.


Asunto(s)
Bartonella , Borrelia burgdorferi , Enfermedad de Lyme , Enfermedades Reumáticas , Humanos , Líquido Sinovial , Estudios Transversales , Estudios Prospectivos , Enfermedad de Lyme/diagnóstico , Inmunoglobulina G , Anticuerpos Antibacterianos , Inmunoglobulina M
13.
Cytokine ; 177: 156564, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38432065

RESUMEN

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.


Asunto(s)
COVID-19 , Humanos , Femenino , Masculino , Interleucina-6 , SARS-CoV-2 , Anticuerpos Antivirales , Inflamación , Inmunoglobulina G , Inmunoglobulina M , Progresión de la Enfermedad
14.
Eur Rev Med Pharmacol Sci ; 28(4): 1314-1326, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38436165

RESUMEN

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.


Asunto(s)
Síndrome Antifosfolípido , Hipertensión Pulmonar , Enfermedad Mixta del Tejido Conjuntivo , Hipertensión Arterial Pulmonar , Esclerodermia Sistémica , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Angioscopía Microscópica , Enfermedad Mixta del Tejido Conjuntivo/complicaciones , Estudios Transversales , Esclerodermia Sistémica/complicaciones , Inmunoglobulina G , Hemorragia , Inmunoglobulina M
15.
Front Immunol ; 15: 1314507, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38487524

RESUMEN

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.


Asunto(s)
Artritis Reumatoide , COVID-19 , Humanos , Factor Reumatoide , Infección Irruptiva , Vacunas contra la COVID-19 , SARS-CoV-2 , COVID-19/prevención & control , Autoanticuerpos , Inmunoglobulina M , Vacunación
16.
Front Immunol ; 15: 1325387, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38469296

RESUMEN

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.


Asunto(s)
Inmunoglobulina G , Vacunas , Humanos , Vacuna BNT162 , Formación de Anticuerpos , Vacunas contra la COVID-19 , Uganda , Vacunación , Anticuerpos Antivirales , Políticas , Inmunoglobulina M
17.
Epidemiol Infect ; 152: e55, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38487841

RESUMEN

Autochthonous hepatitis E virus (HEV) infection is increasingly reported in industrialized countries and is mostly associated with zoonotic HEV genotype 3 (HEV-3). In this study, we examined the molecular epidemiology of 63 human clinical HEV-3 isolates in Canada between 2014 and 2022. Fifty-five samples were IgM positive, 45 samples were IgG positive and 44 were IgM and IgG positive. The majority of the isolates belong to the subtypes 3a, 3b, and 3j, with high sequence homology to Canadian swine and pork isolates. There were a few isolates that clustered with subtypes 3c, 3e, 3f, 3h, and 3g, and an isolate from chronic infection with a rabbit strain (3ra). Previous studies have demonstrated that the isolates from pork products and swine from Canada belong to subtypes 3a and 3b, therefore, domestic swine HEV is likely responsible for the majority of clinical HEV cases in Canada and further support the hypothesis that swine serve as the main reservoirs for HEV-3 infections. Understanding the associated risk of zoonotic HEV infection requires the establishment of sustainable surveillance strategies at the interface between humans, animals, and the environment within a One-Health framework.


Asunto(s)
Virus de la Hepatitis E , Hepatitis E , Enfermedades de los Porcinos , Porcinos , Animales , Humanos , Conejos , Virus de la Hepatitis E/genética , Epidemiología Molecular , Canadá/epidemiología , Hepatitis E/epidemiología , Hepatitis E/veterinaria , Enfermedades de los Porcinos/epidemiología , Genotipo , Inmunoglobulina G , Inmunoglobulina M , Filogenia , ARN Viral/genética
18.
Proc Natl Acad Sci U S A ; 121(13): e2313672121, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38502693

RESUMEN

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.


Asunto(s)
Cambio de Clase de Inmunoglobulina , Células B de Memoria , Humanos , Linfocitos B , Antígenos , Inmunoglobulina G , Inmunoglobulina M , Memoria Inmunológica
19.
Sci Rep ; 14(1): 6151, 2024 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-38486038

RESUMEN

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.


Asunto(s)
Diabetes Mellitus , Internet de las Cosas , Humanos , Femenino , Embarazo , Glucemia , Automonitorización de la Glucosa Sanguínea/métodos , Calidad de Vida , Diabetes Mellitus/terapia , Inmunoglobulina M
20.
PLoS One ; 19(3): e0298730, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38483868

RESUMEN

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.


Asunto(s)
Sarampión , Prueba de Diagnóstico Rápido , Humanos , Inmunoglobulina M , Malasia/epidemiología , Sarampión/diagnóstico , Sarampión/epidemiología , Técnicas para Inmunoenzimas , Sensibilidad y Especificidad
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