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2.
Scand J Immunol ; 90(6): e12828, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31520490

RESUMO

BACKGROUND: Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency. Although most people with selective IgAD (sIgAD) are asymptomatic, many patients often suffer from recurrent respiratory infections and different allergic disorders. Our aim was to investigate connection between subtypes of sIgAD and incidence of respiratory and allergic disorders, as well as connection with lung function changes in children. METHODS: Children with IgAD where divided into two groups; severe IgAD in patients was defined as serum IgA level <7 mg/dL, while partial IgA deficiency diagnosis was made when serum IgA levels was higher than 7 mg/dL but at least two standard deviations (SD) below mean normal concentrations for their age. All patients were evaluated by their clinical and laboratory investigation parameters and compared to control group of children. RESULTS: Group of children with IgAD, severe as well as partial, showed higher prevalence of allergic diseases and total number of infections, compared to controls. There was a statistically significant difference in lung function for peak expiratory flow (PEF), the maximal expiratory flow at 50% of the forced vital capacity (MEF50) and fraction of exhaled nitric oxide (FENO) between group of patients with severe as well as partial IgAD and control group, where children with IgAD showed reduced lung function. CONCLUSIONS: Children with sIgAD are at increased risk for higher number of respiratory infections and developing allergic diseases, resulting in significantly lower pulmonary function which is related with the severity of sIgAD.


Assuntos
Hipersensibilidade/etiologia , Deficiência de IgA/complicações , Doenças Respiratórias/etiologia , Adolescente , Fatores Etários , Biomarcadores , Criança , Pré-Escolar , Feminino , Humanos , Hipersensibilidade/diagnóstico , Deficiência de IgA/diagnóstico , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Masculino , Testes de Função Respiratória , Doenças Respiratórias/diagnóstico , Índice de Gravidade de Doença
3.
J Anim Sci ; 97(11): 4557-4566, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31504564

RESUMO

The present study was conducted to evaluate the effects of dietary garcinol supplementation during late gestation (from the 90th day of pregnancy; day 90) and lactation on the acid-base balance of the umbilical cord blood and performance of sows and piglets. Sixty sows (Duroc × Yorkshire × Landrace; second- or third-parity; n = 20) were randomly divided into 3 gestation (day 90 of pregnancy) or lactation treatments, control diet (CON; basal diet), basal diet with 200 mg garcinol, and basal diet with 600 mg garcinol per kg of feed. The body weight (BW); backfat thickness and litter size of the sows; and birth weight, weaning weight, and mortality of piglets were recorded. Sows' blood and piglets' umbilical cord blood were collected for the measurements of hematological parameters and antioxidative and immune indexes, and acid-base balance parameters, respectively. The colostrum and milk and fecal samples of the sows were also collected for analysis of milk composition and apparent total tract nutrient digestibility. Garcinol had no effect on the BW and backfat thickness of the sows but significantly increased the birth weight and weaning weight of piglets (P < 0.05) and decreased the mortality (P < 0.05). Moreover, the white blood cell counts and neutrophil count, mean cell hemoglobin, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activity in the plasma of the sows were increased more significantly (P < 0.05) in the garcinol groups than that in the CON group, whereas the malondialdehyde (MDA) content was decreased (P < 0.05). The garcinol treatment significantly increased the pH, HCO3- and base excess values (P < 0.05), whereas it decreased the pCO2 and lactate content (P < 0.05) in the umbilical blood. Dry matter (DM), ash, and ether extract in the colostrum were similar between groups (P > 0.05), whereas the garcinol significantly increased the crude protein (CP) in the milk. In addition, the content of immunoglobulin A (IgA) and immunoglobulin G (IgG) in the plasma of piglets and in colostrum and milk of sows were increased more significantly (P < 0.05) in the garcinol groups than that in the CON group. The apparent total tract nutrient digestibility was similar between treatments. Collectively, this study indicates that sows fed with garcinol in late gestation and lactation showed improved maternal health and antioxidative status, milk protein content, acid-base balance in the umbilical cord blood, and growth performance in piglets, showing promise in natural plant extract nutrition for sows.


Assuntos
Suplementos Nutricionais/análise , Leite/química , Suínos/fisiologia , Terpenos/administração & dosagem , Equilíbrio Ácido-Base/efeitos dos fármacos , Ração Animal/análise , Animais , Colostro/química , Dieta/veterinária , Feminino , Sangue Fetal/efeitos dos fármacos , Imunoglobulina A/sangue , Lactação/efeitos dos fármacos , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Paridade , Gravidez , Distribuição Aleatória , Suínos/sangue , Suínos/imunologia , Desmame
4.
Vet Microbiol ; 236: 108387, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31500721

RESUMO

Given the highly contagious and acute nature of porcine epidemic diarrhea (PED), especially in piglets, there is an urgent need for the development of rapid and sensitive diagnostic assays. The diagnostic potentials of specific porcine epidemic diarrhea virus (PEDV) accessory and nonstructural proteins, if any, have not yet been investigated. In order to determine and compare which of the viral proteins may be useful as diagnostic antigens, whole virus (WV) particles and a panel of structural and nonstructural PEDV proteins [spike subunit 1 (S1), the C-terminal part of ORF3 (ORF3C), envelope (E), nonstructural protein 1 (Nsp1), Nsp2, Ac (acidic domain of Nsp3), and ADRP (ADP-ribose-1-monophosphatase domain of Nsp3), expressed individually in bacterial and/or mammalian cells] were tested for reactivity with sera from PEDV-infected pigs by ELISA and/or western blot analysis. According to western blots, serum antibody interactions with the S1 protein were relatively more sensitive and specific than ORF3C, E and Ac. Furthermore, a total of 851 serum samples from diarrheal pigs of different ages were analyzed by ELISA, with most showing immune-reactivity towards the WV, S1, ORF3C, and E proteins. The earliest IgG antibody response was observed in the one-week-old piglets, with similar antibody ontogeny and patterns of seroconversion for S1, ORF3C, E, and WV antigens. In addition, the pattern of neutralizing antibody was more similar to that of IgA in weaning piglets after PEDV infection. Collectively, these data provide more reliable information on the host immune response to different viral proteins, which will be useful for development of novel serological assays and for design of vaccines that better stimulate protective immunity.


Assuntos
Infecções por Coronavirus/veterinária , Vírus da Diarreia Epidêmica Suína/metabolismo , Doenças dos Suínos/virologia , Proteínas Virais/metabolismo , Animais , Anticorpos Antivirais/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Vírus da Diarreia Epidêmica Suína/imunologia , Suínos , Doenças dos Suínos/diagnóstico , Doenças dos Suínos/imunologia , Células Vero , Proteínas Virais/imunologia
5.
Nutrients ; 11(8)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434238

RESUMO

We aimed to estimate the seroprevalence and the prevalence of coeliac disease (CD) in women with reproductive problems. A systematic review of English published articles until June 2019 was performed in PubMed and Scopus using the terms: (infertility and (coeliac disease OR gluten) OR (miscarriage and (coeliac disease OR gluten) OR (abortion and (coeliac disease OR gluten). All articles showing numerical data of anti-transglutaminase type 2 or anti-endomisium antibodies, or intestinal biopsy information were included. The study group comprised women with overall infertility, unexplained infertility, or recurrent spontaneous abortions. Two authors independently performed data extraction using a predefined data sheet. The initial search yielded 310 articles, and 23 were selected for data extraction. After meta-analysis, the pooled seroprevalence was very similar for overall and unexplained infertility, with a pooled proportion of around 1.3%-1.6%. This implies three times higher odds of having CD in infertility when compared to controls. The pooled prevalence could not be accurately calculated due to the small sample sizes. Further studies with increased sample sizes are necessary before giving specific recommendations for CD screening in women with reproductive problems, but current data seem to support a higher risk of CD in these women.


Assuntos
Doença Celíaca/epidemiologia , Infertilidade Feminina/epidemiologia , Aborto Habitual/epidemiologia , Autoanticorpos/sangue , Biópsia , Doença Celíaca/diagnóstico , Doença Celíaca/imunologia , Duodeno/patologia , Grupos Étnicos , Feminino , Proteínas de Ligação ao GTP/imunologia , Humanos , Imunoglobulina A/sangue , Gravidez , Transglutaminases/imunologia
6.
PLoS Negl Trop Dis ; 13(8): e0007634, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31369553

RESUMO

BACKGROUND: Oral cholera vaccine (OCV) containing killed Vibrio cholerae O1 and O139 organisms (Bivalent-OCV; Biv-OCV) are playing a central role in global cholera control strategies. OCV is currently administered in a 2-dose regimen (day 0 and 14). There is a growing body of evidence that immune responses targeting the O-specific polysaccharide (OSP) of V. cholerae mediate protection against cholera. There are limited data on anti-OSP responses in recipients of Biv-OCV. We assessed serum antibody responses against O1 OSP, as well as antibody secreting cell (ASC) responses (a surrogate marker for mucosal immunity) and memory B cell responses in blood of adult recipients of Biv-OCV in Dhaka, Bangladesh. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 30 healthy adults in this study and administered two doses of OCV (Shanchol) at days 0 and 14. Blood samples were collected before vaccination (day 0) and 7 days after each vaccination (day 7 and day 21), as well as on day 44. Serum responses were largely IgA with minimal IgG and IgM responses in this population. There was no appreciable boosting following day 14 vaccination. There were significant anti-OSP IgA ASC responses on day 7 following the first vaccination, but none after the second immunization. Anti-OSP IgA memory B cell responses were detectable 30 days after completion of the vaccination series, with no evident induction of IgG memory responses. In this population, anti-Ogawa OSP responses were more prominent than anti-Inaba responses, perhaps reflecting impact of previous exposure. Serum anti-OSP responses returned to baseline within 30 days of completing the vaccine series. CONCLUSION: Our results call into question the utility of the 2-dose regimen separated by 14 days in adults in cholera endemic areas, and also suggest that Biv-OCV-induced immune responses targeting OSP are largely IgA in this highly endemic cholera area. Studies in children in cholera-endemic areas need to be performed. Protective efficacy that extends for more than a month after vaccination presumably is mediated by direct mucosal immune response which is not assessed in this study. Our results suggest a single dose of OCV in adults in a cholera endemic zone may be sufficient to mediate at least short-term protection.


Assuntos
Formação de Anticorpos , Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Memória Imunológica/imunologia , Membrana Mucosa/imunologia , Antígenos O/imunologia , Vacinação , Vibrio cholerae O1/imunologia , Administração Oral , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Células Produtoras de Anticorpos/imunologia , Linfócitos B/imunologia , Bangladesh , Vacinas contra Cólera/administração & dosagem , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Vibrio cholerae O139/imunologia , Adulto Jovem
7.
Chin Med J (Engl) ; 132(16): 1942-1950, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31365430

RESUMO

BACKGROUND: Henoch-Schonlein purpura nephritis (HSPN) is a very common secondary kidney disease of childhood. Its pathogenesis and the treatment mechanism of glucocorticoid have not been fully elucidated. The aim of this study was to determine the relationship between p300 and the pathogenesis, glucocorticoid therapy in mice with HSPN, respectively. METHODS: Forty-eight C57BL/6N male mice, weighing 18 to 20 g, were selected (3-4 weeks old, n = 8 per group). The mice in the normal control group (Group I) were given normal solvent and the HSPN model group (Group II) were given sensitizing drugs. The mice in Group III were injected intraperitoneally with dexamethasone after being given sensitizing drugs. Meanwhile, mice in Groups IV, V and VI with conditional knockout of p300 were also given normal solvent, sensitizing drugs and dexamethasone.The levels of serum IgA, creatinine, and circulating immune complex (CIC) concentrations, 24 h urinary protein and urinary erythrocyte in C57 wild mice, and p300 conditional knockout mice in each group were measured. The expression of p300 in renal tissues and the expression of glucocorticoid receptor (GR) α and ß, transforming growth factor (TGF)-ß1, and activator protein (AP)-1 after dexamethasone treatment were determined by real-time polymerase chain reaction and Western blotting. RESULTS: Compared with the normal solvent control group (Group I), the expression of p300 mRNA in the model group (Group II) was significantly up-regulated. Western blotting further confirmed the result. Urinary erythrocyte count, 24 h urinary protein quantification, serum IgA, CIC, and renal pathologic score in Group V were distinctly decreased compared with non-knockout mice in Group II (9.7 ±â€Š3.8 per high-power field [/HP] vs. 18.7 ±â€Š6.2/HP, t = 1.828, P = 0.043; 0.18 ±â€Š0.06 g/24 h vs. 0.36 ±â€Š0.08 g/24 h, t = 1.837, P = 0.042; 18.78 ±â€Š0.85 mg/mL vs. 38.46 ±â€Š0.46 mg/mL, t = 1.925, P = 0.038; 0.80 ±â€Š0.27 µg/mL vs. 1.64 ±â€Š0.47 µg/mL, t = 1.892, P = 0.041; 7.0 ±â€Š0.5 vs. 18.0 ±â€Š0.5, t = 1.908, P = 0.039). Compared with non-knockout mice (Group III), the level of urinary erythrocyte count and serum IgA in knockout mice (Group VI) increased significantly after treatment with dexamethasone (3.7 ±â€Š0.6/HP vs. 9.2 ±â€Š3.5/HP, t = 2.186, P = 0.024; 12.38 ±â€Š0.26 mg/mL vs. 27.85 ±â€Š0.65 mg/mL, t = 1.852, P = 0.041). The expression level of GRα was considerably increased in the knockout group after dexamethasone treatment compared with non-knockout mice in mRNA and protein level (t = 2.085, P = 0.026; t = 1.928, P = 0.035), but there was no statistically significant difference in the expression level of GRß between condition knockout and non-knockout mice (t = 0.059, P = 0.087; t = 0.038, P = 1.12). Furthermore, the expression levels of glucocorticoid resistance genes (AP-1 and TGF-ß1) were notably increased after p300 knockout compared with non-knockout mice in mRNA and protein level (TGF-ß1: t = 1.945, P = 0.034; t = 1.902, P = 0.039; AP-1: t = 1.914, P = 0.038; t = 1.802, P = 0.041). CONCLUSIONS: p300 plays a crucial role in the pathogenesis of HSPN. p300 can down-regulate the expression of resistance genes (AP-1 and TGF-ß1) by binding with GRα to prevent further renal injury and glucocorticoid resistance. Therefore, p300 is a promising new target in glucocorticoid therapy in HSPN.


Assuntos
Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Nefrite/tratamento farmacológico , Nefrite/metabolismo , Púrpura de Schoenlein-Henoch/tratamento farmacológico , Púrpura de Schoenlein-Henoch/metabolismo , Fatores de Transcrição de p300-CBP/metabolismo , Animais , Creatinina/sangue , Humanos , Imunoglobulina A/sangue , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nefrite/sangue , Nefrite/genética , Púrpura de Schoenlein-Henoch/sangue , Púrpura de Schoenlein-Henoch/genética , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Fatores de Crescimento Transformadores/genética , Fatores de Crescimento Transformadores/metabolismo , Fatores de Transcrição de p300-CBP/genética
8.
J Vet Med Sci ; 81(9): 1249-1258, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31341112

RESUMO

Inflammatory bowel disease (IBD) is a common gastrointestinal disease in dogs. Decreased production of intestinal immunoglobulin A (IgA) has been suggested as a possible pathogenesis in a subset of canine IBD; however, the underlying cause remains unclear. Sphingosine-1-phosphate (S1P) is a lipid mediator that regulates intestinal IgA production by controlling lymphocyte trafficking in mice. The objectives of this study were to clarify the role of S1P in IgA production in dogs and to evaluate the expression of S1P-related molecules in dogs with IBD. First, an S1P receptor antagonist was administrated to five healthy dogs. The S1P receptor antagonist significantly decreased the IgA concentration in sera and feces but did not affect the IgG concentration. Moreover, the immunoreactivity of intestinal IgA was significantly decreased by S1P signal blockade. These results indicate that S1P signaling specifically regulates the intestinal IgA production in dogs. Subsequently, the intestinal S1P concentration and the expression of S1P-related molecules were measured in dogs with IBD and healthy dogs. The intestinal concentration of S1P was significantly lower in dogs with IBD than in healthy dogs. In addition, the gene expression levels of S1P receptor (S1P1) and S1P synthase (SK1) were significantly lower in dogs with IBD than in healthy dogs. Taken together, these observations suggest that decreased S1P production, likely caused by a lower expression of S1P synthetase, leads to attenuation of S1P/S1P1 signaling pathway and the production of intestinal IgA in dogs with IBD.


Assuntos
Doenças do Cão/metabolismo , Imunoglobulina A/metabolismo , Doenças Inflamatórias Intestinais/veterinária , Lisofosfolipídeos/metabolismo , Esfingosina/análogos & derivados , Animais , Doenças do Cão/patologia , Cães , Fezes/química , Cloridrato de Fingolimode/administração & dosagem , Expressão Gênica , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Intestinos/química , Masculino , Esfingosina/metabolismo , /genética
9.
Clin Lab ; 65(7)2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31307156

RESUMO

BACKGROUND: Hyper-IgA is not a rare finding in children although its causes are less reported than hypergamma-globulinemia in other classes of immunoglobulin. However, an isolated hyper-IgA might play a role as a diagnostic marker, in particular in children with an incomplete clinical picture at disease onset. RESULTS: We reported the case of a 3-year-old girl hospitalized for acute abdominal symptoms and suspicion of ruptured appendicitis. She presented severe inflammatory syndrome and her medical history related recurrent fever episodes. Serum immunoglobulin analysis was not in favor of an infection; indeed, IgA concentration alone increased and reached a surprising extremely high value in a young child (17-fold of the upper reference value). CONCLUSIONS: This case highlights the potential clinical significance of an isolated hyper-IgA that is known to be mostly found in serious diseases in children; it might contribute to reduce the delay in diagnosis and treatment of hyperimmunoglobulinemia D syndrome, an autoinflammatory disease.


Assuntos
Apendicite/diagnóstico , Hipergamaglobulinemia/diagnóstico , Imunoglobulina A/sangue , Apendicite/sangue , Pré-Escolar , Feminino , Humanos , Hipergamaglobulinemia/sangue , Síndrome
10.
Dis Markers ; 2019: 2407067, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275443

RESUMO

Background: Galactose-deficient IgA1 (Gd-IgA1) is an important causal factor in IgA nephropathy; however, the underlying mechanism for the production of Gd-IgA1 is unknown. The elongation factor for RNA polymerase II (ELL2), which encoded a key component of the superelongation complex (SEC), drives secretory-specific Ig mRNA production. Methods: We enrolled 21 patients with IgAN, 18 healthy controls, and 20 patients with non-IgAN glomerulonephritis. The differential expression of ELL2 was compared using publically available data from Gene Expression Omnibus (GEO) datasets. The relationship between ELL2 expressions and galactose-deficient IgA1 (Gd-IgA1) levels in serum were also studied. At last, the results were validated by shELL2 treatment experiment. Results: We found that the number of CD19+ B cells was increased in IgAN patients compared to healthy controls. The expression level of ELL2 in patients with IgAN was significantly lower than that of healthy control and disease control. Consistent with present results, the lower ELL2 expression in IgAN patients was observed in microarray expression profiles from GEO datasets. Pearson correlation analysis showed that ELL2 expression negatively correlated with Gd-IgA1 levels. Furthermore, in an in vitro experiment, we found that loss of ELL2 function in human B lymphoma DAKIKI cells, an IgA1-producing cell line, increased the levels of Gd-IgA1, which confirmed that ELL2 modulated the levels of Gd-IgA1. Conclusion: Our findings implied that decreased ELL2 expression was negatively correlated with the numbers of B cells and aberrant glycosylation of IgA1 in IgAN.


Assuntos
Glomerulonefrite por IGA/sangue , Imunoglobulina A/sangue , Fatores de Elongação da Transcrição/sangue , Adulto , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Galactose/metabolismo , Humanos , Imunoglobulina A/metabolismo , Masculino , Pessoa de Meia-Idade , Processamento de Proteína Pós-Traducional , Fatores de Elongação da Transcrição/genética , Fatores de Elongação da Transcrição/metabolismo
11.
Indian J Pathol Microbiol ; 62(3): 441-444, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31361235

RESUMO

Light chain myeloma (LCM) has a reported worldwide incidence of approximately 15%-20% among all multiple myeloma (MM) patients. Few western studies have shown strong correlation of LCM with anemia, higher International Staging System scores, proclivity to renal failure, elevated lactate dehydrogenase levels, raised serum-free light chain ratio, higher frequency of extramedullary plasmacytomas, and poorer overall survival, attributable probably to lack of differentiation and skeletal destruction. The primary aim of this retrospective observational study was to define the clinical and hematological characteristics as well as prognostic outcome of Indian LCM patients in comparison with the IgG and IgA subtypes. Patients were defined according to the International Myeloma Working Group diagnostic criteria 2016 and staged as per the International Staging System. Out of 104 patients of newly diagnosed MM in which results of serum immunofixation (IFE) were available, 65 were of IgG isotype (62.5%), 15 had IgA (14.4%), and 24 had light chain myelomas (LCMs) (23.1%). It was observed that LCM patients significantly correlated with hypercalcemia and higher serum-free light chain ratios, whereas IgA patients were strongly associated with anemia and lower serum albumin levels. However, no difference was found among the three subgroups in terms of serum lactate dehydrogenase levels, proclivity to renal failure, presence of lytic bone lesions, prognostic scoring, pretransplant chemosensitivity, and progession-free survival (1 year). Thus, it may be concluded that Indian LCM patients have significantly different clinico-hematological profile in comparison with other published studies worldwide. Also, their prognostic outcomes are not worse when compared with patients of other protein isotypes, probably due to standardized treatment regimens applied.


Assuntos
Imunoglobulina A/sangue , Imunoglobulina G/sangue , Cadeias Leves de Imunoglobulina/sangue , Mieloma Múltiplo/complicações , Mieloma Múltiplo/imunologia , Idoso , Anemia/etiologia , Feminino , Humanos , Hipercalcemia/etiologia , Índia , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Plasmocitoma , Prognóstico , Estudos Retrospectivos , Albumina Sérica/análise
12.
Dis Markers ; 2019: 9802839, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354895

RESUMO

Background: It has been suggested that mesangial IgA deposits are dimeric or polymeric in IgA nephropathy (IgAN). However, evidence concerning the molecular form of serum IgA in IgAN is controversial. And there is no direct evidence that the serum levels of joining chain- (J chain-) containing IgA (J-IgA) are elevated in IgAN. In this study, we aimed to measure serum J-IgA and glomerular J chain deposition with anti-J chain monoclonal antibody in IgAN. Methods: BALB/c mice were immunized with human J chain-GST recombinant peptide to obtain anti-J chain monoclonal antibody. The levels of serum total IgA and J-IgA were measured by sandwich enzyme-linked immunosorbent assay in 115 patients with IgAN and 117 healthy volunteers. J chain deposition in kidney specimens was analyzed by immunohistochemistry staining. Results: Serum levels of total IgA1 were elevated in IgAN patients compared to healthy subjects. However, serum levels of IgA, J-IgA, and J chain-containing IgA1 (J-IgA1), the J-IgA to total IgA ratio, and the J-IgA1 to total IgA1 ratio were not significantly different between IgAN patients and healthy subjects. Western blot analysis and gel filtration analysis using purified IgA1 also showed that the proportion of J chain-containing polymeric IgA1 was lower in IgAN patients compared to healthy subjects. No correlation was found between serum J-IgA or J-IgA1 and clinical features in IgAN. Immunohistochemistry analysis showed that glomerular J chain was positive in 12 IgAN patients (57.1%). The values of the J-IgA to IgA ratio and J-IgA1 to IgA ratio were significantly higher in IgAN patients with glomerular J chain deposition than those without. However, the serum levels of J-IgA and J-IgA1 and the J-IgA1 to IgA1 ratio were not significantly higher in two subgroups. Conclusions: Although serum levels of total IgA1 were elevated in IgAN, the serum levels of J-IgA1 were not elevated. And serum J-IgA, serum J-IgA1, and J chain deposition were not correlated with disease severity in IgAN.


Assuntos
Glomerulonefrite por IGA/sangue , Imunoglobulina A/sangue , Cadeias J de Imunoglobulina/sangue , Adulto , Animais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
13.
Microb Pathog ; 134: 103600, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202906

RESUMO

INTRODUCTION: Severe intestinal infections caused by V. cholerae, ETEC and EHEC have contributed to the mortality rate in developing countries. Vibrio Cholera, ETEC and EHEC bacterium with the production of CT, LT and Stx2 toxins respectively lead to severe watery and bloody diarrhea. This study aimed to investigate a trimeric vaccine candidate containing recombinant chimeric protein, encapsulate the protein in chitosan nanoparticles and assess its immunogenicity. METHODS: The LSC recombinant gene was used. It is composed of LTB (L), STXB (S) and CTXB (C) subunits respectively. The LSC recombinant protein was expressed and purified and confirmed by western blotting. The purified protein was encapsulated in chitosan nanoparticles, and its size was measured. BalB/c mice were immunized in four groups through oral and injection methods by LSC protein. The antibody titer was then evaluated by ELISA, and finally, the challenge test of the toxins from all three bacteria was done on the immunized mouse. RESULTS: After expression and purification LSC protein size of nanoparticles containing protein was measured at 104.6 nm. Nanoparticles were able to induce systemic and mucosal immune responses by generating a useful titer of IgG and IgA. The challenge results with LT, CT and Stx toxins showed that the LSC protein might partially neutralize the effect of toxins. CONCLUSION: LSC chimeric protein with the simultaneous three essential antigens have a protective effect against the toxins produced by ETEC, EHEC and Vibrio cholera bacteria and it can be used in vaccines to prevent Diarrhea caused by these three bacteria.


Assuntos
Toxinas Bacterianas/imunologia , Vacinas Bacterianas/imunologia , Quitosana/farmacologia , Imunização , Nanopartículas/química , Proteínas Recombinantes de Fusão/imunologia , Vacinação , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Toxinas Bacterianas/genética , Toxinas Bacterianas/isolamento & purificação , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/genética , Toxina da Cólera/genética , Toxina da Cólera/imunologia , Diarreia/microbiologia , Diarreia/prevenção & controle , Modelos Animais de Doenças , Escherichia coli Êntero-Hemorrágica/genética , Escherichia coli Êntero-Hemorrágica/imunologia , Escherichia coli Enterotoxigênica/genética , Escherichia coli Enterotoxigênica/imunologia , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/prevenção & controle , Regulação Bacteriana da Expressão Gênica , Imunidade nas Mucosas , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Proteínas Recombinantes de Fusão/genética , Toxinas Shiga/genética , Toxinas Shiga/imunologia , Análise de Sobrevida , Vibrio cholerae/genética , Vibrio cholerae/imunologia
14.
Biosens Bioelectron ; 141: 111357, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31170501

RESUMO

The development of versatile platforms to construct novel and sensitive immunosensors is nowadays an intense research field. Nanomaterials and polymers are often combined to fabricate new platforms to immobilize capture antibodies. Here we evaluate for the first time the co-electropolymerization of dopamine (DA) and L-3,4-dihydroxyphenylalanine (L-DOPA) on carbon nano-onion (CNO) modified electrodes as versatile platform to develop electrochemical immunosensors. Mixtures of DA and L-DOPA at different molar rations were co-electropolymerized on CNO-modified glassy carbon electrodes to form a poly(L-DOPA/DA) film. Immobilization of aminoferrocene was used to estimate the number of accessible carboxylic acid groups on the surface (11.3 nmol/cm2), a value comparable to three-dimensional matrices. This platform was applied to the electrochemical detection of IgA antibodies using both a HRP-based sandwich type assay and label-free detection based on [Fe(CN)6]3-/4- signal blocking. The sandwich and the label-free assays showed a wide linear response with LOD of 19 and 48 ng/mL, respectively, allowing the detection of serum IgA deficiency. Most remarkably, the incorporation of CNO layer led to a significant improvement (three-orders of magnitude) of the analytical performance of these immunosensors due to a combination of high surface area and increased electron transfer rates provided by the CNO layer.


Assuntos
Técnicas Biossensoriais/métodos , Carbono/química , Dopamina/química , Imunoglobulina A/sangue , Levodopa/química , Anticorpos Imobilizados/química , Eletrodos , Humanos , Imunoensaio/métodos , Limite de Detecção , Modelos Moleculares , Nanoestruturas/química , Polimerização , Polímeros/química
15.
Arab J Gastroenterol ; 20(2): 95-98, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31182344

RESUMO

BACKGROUND AND STUDY AIMS: Juvenile idiopathic arthritis (JIA) is characterized by autoimmune aetiology. A gene locus 4q27 related to rheumatoid arthritis, psoriatic arthritis, and coeliac disease is associated with susceptibility to JIA. There are reports indicating several patients with JIA had been diagnosed with CD. We aimed to assess the frequency of coeliac disease (CD) in patients with juvenile idiopathic arthritis (JIA). PATIENTS AND METHODS: This prospective study was carried out from October 2015 to August 2016 and included 96 patients with JIA. All patients were evaluated in terms of clinical and laboratory findings of CD. Levels of total IgA and tissue transglutaminase antibody (tTG) IgA were measured in all patients. Those with increased level of tTG IgA were further tested for anti-endomysium IgA antibodies (EMA). Gastroduodenoscopy were planned for a definite diagnosis of CD in patients with positive EMA. RESULTS: Of the 96 patients in our study, 34 (35.4%) had oligoarticular form of JIA, 29 (30.2%) had polyarticular form, 12 (12.5%) had ERA form, 11 (11.5%) had systemic form, and 10 (10.4%) had psoriatic form. Sixteen of our patients (16.6%) were not using any drugs during the study. Neither EMA IgA antibodies were analysed nor gastro-duodenoscopy was performed because no patients were positive for tTG IgA. There was no difference in terms of tTG levels between the patients using NSAIDs or other drugs. CONCLUSION: We did not find CD in children with JIA. Long term studies with more JIA patients are needed to provide more precise interpretation.


Assuntos
Artrite Juvenil/epidemiologia , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Adolescente , Artrite Juvenil/sangue , Artrite Juvenil/tratamento farmacológico , Doença Celíaca/sangue , Criança , Comorbidade , Feminino , Proteínas de Ligação ao GTP/imunologia , Humanos , Imunoglobulina A/sangue , Incidência , Masculino , Estudos Prospectivos , Transglutaminases/imunologia , Turquia/epidemiologia
16.
Rev Inst Med Trop Sao Paulo ; 61: e30, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31241659

RESUMO

Toxoplasma gondii can cross the placental barrier, causing fetal infection with potentially severe sequelae. The aim of this study was to evaluate whether the serological screening for toxoplasmosis should be included in the basic neonatal heel prick test in order to establish criteria for the confirmation and/or exclusion of the diagnosis of congenital infection in newborns treated at three public health units in the metropolitan region of Goiania, Goias State, Brazil. Blood samples were collected on filter paper from newborns and later, peripheral blood samples from the mothers and their respective children were obtained to confirm or exclude the diagnosis of suspected congenital infection, by means of an enzyme-linked immunosorbent assay (IgM and IgG) and a polymerase chain reaction assay. From a total of 1,159 blood samples collected on filter paper, 43.92% were reactive to IgG and 0.17% to anti-T. gondii IgM and IgG. One hundred and twenty-seven paired samples (mother and child) were collected following consensual protocols for peripheral blood collection. Results obtained from the filter paper and peripheral blood of the newborns were 90.55% concordant. A comparison of the mother and child blood test results showed agreement regarding the detection of IgG in 90.48% of the samples. The parasite DNA was detected in the peripheral blood of one child. In view of the results obtained in this study, the inclusion of the serological screening for toxoplasmosis in the newborn heel prick test proved to be effective for the early detection of congenital T. gondii infection.


Assuntos
Triagem Neonatal/métodos , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/diagnóstico , Toxoplasma/microbiologia , Toxoplasmose Congênita/sangue , Toxoplasmose Congênita/diagnóstico , Anticorpos Antiprotozoários/sangue , Brasil , Feminino , Doenças Fetais , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Reação em Cadeia da Polimerase , Gravidez , Complicações Infecciosas na Gravidez/genética , Estudos Prospectivos , Toxoplasma/genética , Toxoplasmose Congênita/genética
17.
Clinics (Sao Paulo) ; 74: e631, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31241661

RESUMO

OBJECTIVE: Primary Sjögren's syndrome (pSjS) is a chronic autoimmune disease that causes dry eye and mouth. No laboratory parameters to monitor the activation of this disease have been identified. Therefore, any possible relationships between salivary and blood myxovirus resistance 1 (MX1) and pSjS must be prospectively studied. METHODS: Thirty female patients with pSjS, 30 women with rheumatoid arthritis (RA) without secondary Sjögren's syndrome (SjS) and 28 healthy control women were enrolled in this investigation. Analyses of MX1 by the enzyme-linked immunosorbent assay (ELISA) method, SS-A (Ro) and SS-B (La) tests by the strip immunoblot method, anti-nuclear antibody (ANA) tests by immunofluorescence and the measurement of serum rheumatoid factor (RF), C3, C4, immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) were performed. RESULTS: The serum level of MX1 in patients without Raynaud phenomenon was higher than in those with Raynaud phenomenon (p:0.029, p<0.05, statistically significant). There was a statistically significant positive association between hemoglobin levels and MX1 serum levels. No statistically significant association was found among the other parameters. Low MX1 levels were shown to be associated with both a low disease activity score based on the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and hydroxychloroquine use in all patients. CONCLUSION: MX1 levels have a considerable impact on the assessment of the disease activity in SjS. We believe that more-comprehensive studies should be performed on patients with pSjS who do not use hydroxychloroquine to prove this relationship and that MX1 levels should be used as a routine marker for the assessment of pSjS disease activity. Further studies are needed to create awareness of the role that MX1 has in the diagnosis of pSjS, which may help to uncover novel pathways for new therapeutic modalities.


Assuntos
Isotipos de Imunoglobulinas/sangue , Proteínas de Resistência a Myxovirus/imunologia , Saliva/química , Síndrome de Sjogren/metabolismo , Adulto , Anticorpos Antinucleares/sangue , Biomarcadores/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Pessoa de Meia-Idade , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia
18.
Gastroenterol Clin North Am ; 48(2): 307-317, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31046977

RESUMO

Most patients affected by celiac disease (CD) are asymptomatic or hyposymptomatic and undiagnosed, and are at risk of preventable complications. Therefore, early diagnosis is highly recommended. Multiple diagnostic antibodies are available; the most frequently used is IgA to tissue transglutaminase (IgA-tTg). It may yield false results and, alone, does not address IgA deficiency. Recently, a new generation of anti-neo-epitope tTg check (IgG + IgA) has become available. It is highly sensitive and specific, covers IgA-deficient patients with CD, reflects intestinal damage, and has predictive potential in the diagnosis of CD.


Assuntos
Biomarcadores/sangue , Doença Celíaca/diagnóstico , Testes Sorológicos/métodos , Diagnóstico Precoce , Proteínas de Ligação ao GTP/imunologia , Gliadina/imunologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Transglutaminases/imunologia
19.
Ren Fail ; 41(1): 370-376, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31057023

RESUMO

BACKGROUND: Recent genomewide association study suggested that the top single-nucleotide polymorphism, rs978056, in HECW1 gene (which encodes HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1) associated with the levels of galactose-deficient IgA1 (Gd-IgA1) in IgA nephropathy (IgAN). However, HECW1 expression in IgAN has not yet been examined. METHODS: In the following study, we have enrolled 40 patients with IgAN and 40 healthy controls. The expression level of HECW1, as well as plasma levels of Gd-IgA1 and IgA1, were determined detected. RESULTS: IgAN patients presented with significantly elevated Gd-IgA1 and IgA1 levels compared with those of the healthy controls (p < .001 and p = .03, respectively). We further divided the patients into two groups according to the median level of HECW1 (0.58). We found the levels of Gd-IgA1 and IgA1 were significantly higher in low HECW1 level group compared with those in high HECW1 level group (p = .02 and p = .04, respectively). And HECW1 mRNA expression had a significant inverse correlation with Gd-IgA1 levels in IgAN patients (r= -0.34, p = .03). It seemed that the risk genotype (rs978056 GG) was associated with reduced HECW1 expression in 80 Han Chinese from Beijing, although the difference was not significant (p = .09). No significant association with clinical and pathological manifestations was observed between patients with high and low levels of HECW1. CONCLUSION: We reported for the first time that HECW1 mRNA levels were negatively correlated with Gd-IgA1 levels. Our study points to a new regulatory mechanism of IgAN that can explain the aberrant glycosylation of IgA1.


Assuntos
Glomerulonefrite por IGA/sangue , Imunoglobulina A/metabolismo , Proteínas do Tecido Nervoso/sangue , Ubiquitina-Proteína Ligases/sangue , Adulto , Linfócitos B/metabolismo , Biópsia , Feminino , Mesângio Glomerular/patologia , Glomerulonefrite por IGA/patologia , Glicosilação , Humanos , Imunoglobulina A/sangue , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , RNA Mensageiro/sangue , RNA Mensageiro/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
20.
Ren Fail ; 41(1): 334-339, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31057050

RESUMO

BACKGROUND: The pathogenesis of the development of IgA nephropathy has not been clear up to now. At present, some studies revealed that the mTOR pathway may participate in IgA nephropathy; however, the mechanism has not been systematically studied. In this study, we established an IgAN rat model to investigate the protective effects of rapamycin as a new type of immunosuppressant, as well as its therapeutic mechanisms. METHODS: After the establishment of IgA nephropathy model, rats were treated with different concentrations of rapamycin, and the protective effect of different concentrations of rapamycin on renal function of the rats was observed. The deposition of IgA was observed by immunofluorescence. The kidney expression of Akt and p70S6k proteins in mTOR pathway was examined using the western blot assay after rapamycin treatment. RESULTS: Morphology and immunofluorescence confirmed that the rat model of IgA nephropathy was successfully established. In particular, the level of proteinuria decreased with the increase of the dose of rapamycin, as well as the deposition of IgA in glomeruli. Moreover, the western blot analysis indicated that the expression of p70S6K in the downstream of mTOR pathway decreased and the upstream protein AKT of the mTOR pathway was overexpressed in the rats model. CONCLUSION: We found that rapamycin has protective effects in the IgA nephropathy rat model in a dose-dependent manner. In addition, the result of western blot assay suggested that rapamycin may display its therapeutic effects through interfering the AKT-mTOR-p70S6K signaling pathway.


Assuntos
Glomerulonefrite por IGA/prevenção & controle , Imunoglobulina A/sangue , Imunossupressores/administração & dosagem , Sirolimo/administração & dosagem , Animais , Modelos Animais de Doenças , Progressão da Doença , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/etiologia , Humanos , Imunoglobulina A/imunologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/patologia , Masculino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Resultado do Tratamento
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