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1.
Mymensingh Med J ; 29(1): 156-161, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31915352

RESUMO

Sub clinical hypothyroidism (SCH) is common in clinical practice. Autoimmunity is thought to be the most important cause of SCH. In this cross-sectional study, we investigated 120 SCH patients and 100 healthy controls attending the Endocrinology Outpatient Department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from June 2014 to April 2015 for anti-thyroid antibodies (anti-TPO and anti-Tg). Measurement of serum TSH, FT4, anti-TPO, and anti-Tg antibodies were done by using the chemiluminescent sequential immunometric assay. SCH patients had a higher mean age; the frequencies of female subjects, those having family history of thyroid disease or other autoimmune diseases, and goiter were higher in SCH group than in the control group. Forty-five percent (45%) of SCH patients were positive for anti-thyroid antibodies (23.3% for both anti-TPO and anti-Tg, 16.7% for only anti-TPO, and 5% positive for only anti-Tg) in comparison to only 10% anti-thyroid antibody positive controls (none for both antibodies, 8% for only anti-TPO, and 2% positive for only anti-Tg). The SCH subjects in the lower age group, females and with a TSH >10µIU/mL had the higher frequency of thyroid autoimmunity. Female gender, high socioeconomic condition, the presence of other autoimmune diseases, the presence of goiter and TSH >10µIU/mL were associated with higher odds of anti-thyroid antibody positivity in the SCH group, though none were statistically significant. The frequency of anti-thyroid antibody was higher in SCH and was more prevalent among the females, younger patients and those having a goiter, other autoimmune diseases, and TSH >10µIU/mL.


Assuntos
Anticorpos/sangue , Autoanticorpos/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/imunologia , Adulto , Autoantígenos , Bangladesh/epidemiologia , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Hipotireoidismo/epidemiologia , Iodeto Peroxidase , Proteínas de Ligação ao Ferro , Prevalência , Tireoglobulina/sangue , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
2.
Einstein (Sao Paulo) ; 18: eRC4582, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31531557

RESUMO

The correct identification of erythrocyte antibodies is fundamental for the searching for compatible blood and haemolytic transfusion reactions prevention. Antibodies against antigens of high prevalence are difficult to identify because of the rarity of their occurrence and unavailability of negative red cells for confirmation. We report a case of 46-years-old woman, diagnosed with hemoglobinopathy, and who had symptomatic fall in hemoglobin levels (5.3g/dL) after blood transfusion suggestive of transfusion reaction. The patient's blood type was O RhD-positive. Irregular antibody screening was positive and demonstrated a panreaction against all erythrocytes tested, but this result was not reactive with dithiothreitol. Using negative red cells for antigens of high prevalence of our inventory we could identify in the serum of the same erythrocytes an anti-Holley antibody associated with anti-E. Molecular analysis confirmed that the patient was negative for E and Holley antigens. The crossmath with compatible units confirmed the results. Holley is a high prevalence antigen of the Dombrock blood system whose negative phenotype is extremely rare in all populations and is associated with hemolytic transfusion reactions. This is an antibody that is difficult to identify because laboratories need to have experience in solving complex cases, and have available a large stock of rare sera and erythrocytes, as well other tools such as enzymes, thiol reagents and molecular tests. The correct identification of a rare antibody is initial and mandatory for searching of compatible donors, and to guarantee a satisfactory transfusional support.


Assuntos
Anticorpos/imunologia , Antígenos de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Reação Transfusional/imunologia , Anticorpos/sangue , Eritrócitos/imunologia , Feminino , Testes Hematológicos/métodos , Humanos , Imunoglobulinas/sangue , Isoanticorpos/imunologia , Pessoa de Meia-Idade
3.
Medicine (Baltimore) ; 98(51): e18334, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860986

RESUMO

The aim of this study was to evaluate the effectiveness of hospital-based hepatitis C epidemic surveillance initiated by China's CDC STD/AIDS (National Center for AIDS/STD Control and Prevention of Chinese Center for Disease Control and Prevention) Prevention and Control Center in 2017.A total of 104,666 anti-hepatitis C virus (HCV) and 633 HCV-RNA detection records in our hospital from 2014 to 2017 were used to analyze the anti-HCV and HCV-RNA detection rates and positive rates in patients before and after implementation of epidemic surveillance.We found that the estimated HCV positive rate was 0.395% in all patients, and this rate increased to 0.533% after the pilot research. The positive rates of anti-HCV were significantly enhanced, although certain differences were observed among different departments. Significant increase of positive rate of HCV-RNA was only found in the inpatients from nonsurgical departments. Eighty-one cases were diagnosed after this pilot research, exceeding the 70 total cases in the previous 3 years. Most cases were diagnosed by nonsurgical departments; the upward trend of the cases diagnosed by surgical departments cannot be ignored.Our study indicates expanding anti-HCV and HCV-RNA detection in the target populations in hospitals is a useful strategy for finding more occult HCV infection. In addition, our results provide useful pilot data of the seroepidemiology of Hepatitis C for the special populations in hospitals, which will provide valuable information for public health research.


Assuntos
Hepatite C/diagnóstico , Hepatite C/epidemiologia , Vigilância da População , Anticorpos/sangue , China/epidemiologia , Hepacivirus/genética , Hepacivirus/imunologia , Humanos , Imunoglobulina G/imunologia , Pacientes Internados , Pacientes Ambulatoriais , Projetos Piloto , RNA Viral/sangue , Estudos Soroepidemiológicos
4.
BMC Infect Dis ; 19(1): 970, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722678

RESUMO

BACKGROUND: Acute febrile illness (AFI) is characterized by malaise, myalgia and a raised temperature that is a nonspecific manifestation of infectious diseases in the tropics. The lack of appropriate diagnostics for the evaluation of AFI leads to increased morbidity and mortality in resource-limited settings, specifically low-income countries like India. The review aimed to identify the number, type and quality of diagnostics used for AFI evaluation during passive case detection at health care centres in South India. METHODS: A scoping review of peer-reviewed English language original research articles published between 1946-July 2018 from four databases was undertaken to assess the type and number of diagnostics used in AFI evaluation in South India. Results were stratified according to types of pathogen-specific tests used in AFI management. RESULTS: The review included a total of 40 studies, all conducted in tertiary care centres (80% in private settings). The studies demonstrated the use of 5-22 tests per patient for the evaluation of AFI. Among 25 studies evaluating possible causes of AFI, 96% tested for malaria followed by 80% for dengue, 72% for scrub typhus, 68% for typhoid and 60% for leptospirosis identifying these as commonly suspected causes of AFI. 54% studies diagnosed malaria with smear microscopy while others diagnosed dengue, scrub typhus, typhoid and leptospirosis using antibody or antigen detection assays. 39% studies used the Weil-Felix test (WFT) for scrub typhus diagnosis and 82% studies used the Widal test for diagnosing typhoid. CONCLUSIONS: The review demonstrated the use of five or more pathogen-specific tests in evaluating AFI as well as described the widespread use of suboptimal tests like the WFT and Widal in fever evaluation. It identified the need for the development of better-quality tests for aetiological diagnosis and improved standardised testing guidelines for AFI.


Assuntos
Doenças Transmissíveis/diagnóstico , Anticorpos/sangue , Antígenos/análise , Dengue/diagnóstico , Humanos , Índia , Leptospirose/diagnóstico , Malária/diagnóstico , Tifo por Ácaros/diagnóstico , Centros de Atenção Terciária
5.
Chem Asian J ; 14(23): 4268-4273, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31591824

RESUMO

The 9-mer peptide MFCH401 (N: 165-173: DTILWKDIF), which is located in the extracellular domain of HER2, has been predicted to be a novel epitope. Self-adjuvanting anti-HER2 vaccine constructs were designed and synthesized via covalently attaching MFCH401 or its linear tandem repeats (2×MFCH401, 3×MFCH401) to a lipopeptide Pam3 CSK4 via iterative condensation reaction. The in vivo results showed the Pam3 CSK4 -MFCH401 vaccine construct can induce higher antibody titers of IgG and IgM than those of other conjugates, and the analysis of changes in plasma cytokines level indicate the activation of Th1 cells and NK cells. In addition, the Pam3 CSK4 -MFCH401 vaccine conjugate induced a specific immune response to HER2-overexpressing human BT474 cells. Our data clearly indicated that MFCH401 is a promising epitope; moreover, its linear tandem repeats were unsuitable for anticancer vaccine design when conjugating with Pam3 CSK4 , which provided useful evidence for developing further anti-HER2 cancer vaccines.


Assuntos
Vacinas Anticâncer/imunologia , Peptídeos/imunologia , Animais , Anticorpos/sangue , Anticorpos/imunologia , Anticorpos/metabolismo , Vacinas Anticâncer/química , Linhagem Celular Tumoral , Citocinas/metabolismo , Humanos , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Camundongos , Peptídeos/síntese química , Peptídeos/química , Receptor ErbB-2/química , Células Th1/citologia , Células Th1/imunologia , Células Th1/metabolismo
6.
Gastroenterology ; 157(5): 1338-1351.e8, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31401142

RESUMO

BACKGROUND & AIMS: Some patients develop anti-drug antibodies (ADAs), which reduce the efficacy of infliximab, a monoclonal antibody against tumor necrosis factor (TNF), in the treatment of immune-mediated diseases, including inflammatory bowel diseases. ADAs arise inconsistently, and it is not clear what factors determine their formation. We investigated features of the immune system, the infliximab antibody, and its complex with TNF that might contribute to ADA generation. METHODS: C57BL/6 mice were given injections of infliximab and recombinant human TNF or infliximab F(ab')2 fragments. Blood samples were collected every 2-3 days for 2 weeks and weekly thereafter for up to 6 weeks; infliximab-TNF complexes and ADAs were measured by enzyme-linked immunosorbent assay (ELISA). Intestinal biopsy and blood samples were obtained from patients having endoscopy who had received infliximab therapy for inflammatory bowel diseases; infliximab-TNF complexes were measured with ELISA. Infliximab-specific plasma cells were detected in patient tissue samples by using mass cytometry. We studied activation of innate immune cells in peripheral blood mononuclear cells (PBMCs) from healthy donors incubated with infliximab or infliximab-TNF complexes; toll-like receptors (TLRs) were blocked with antibodies, endocytosis was blocked with the inhibitor PitStop2, and cytokine expression was measured by real-time polymerase chain reaction and ELISAs. Uptake of infliximab and infliximab-TNF complexes by THP-1 cells was measured with confocal microscopy. RESULTS: Mice given increasing doses of infliximab produced increasing levels of ADAs. Blood samples from mice given injections of human TNF and infliximab contained infliximab-TNF complexes; complex formation was associated with ADA formation with an area under the curve of 0.944 (95% confidence interval, 0.851-1.000; P = .003). Intestinal tissues from patients, but not blood samples, contained infliximab-TNF complexes and infliximab-specific plasma cells. Incubation of PBMCs with infliximab-TNF complexes resulted in a 4.74-fold increase in level of interleukin (IL) 1ß (IL1B) messenger RNA (P for comparison = .005), increased IL1B protein secretion, and a 2.69-fold increase in the expression of TNF messenger RNA (P for comparison = 0.013) compared with control PBMCs. Infliximab reduced only IL1B and TNF expression. Antibodies against TLR2 or TLR4 did not block the increases in IL1B or TNF expression, but endocytosis was required. THP-1 cells endocytosed higher levels of infliximab-TNF complexes than infliximab alone. CONCLUSIONS: In mice, we found ADA formation to increase with dose of infliximab given and concentration of infliximab-TNF complexes detected in blood. Based on studies of human intestinal tissues and blood samples, we propose that infliximab-TNF complexes formed in the intestine are endocytosed by and activate innate immune cells, which increase expression of IL1B and TNF and production of antibodies against the drug complex. It is therefore important to optimize the infliximab dose to a level that is effective but does not activate an innate immune response against the drug-TNF complex.


Assuntos
Anticorpos/sangue , Fragmentos Fab das Imunoglobulinas/imunologia , Doenças Inflamatórias Intestinais/imunologia , Infliximab/imunologia , Intestinos/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Estudos de Casos e Controles , Endocitose , Feminino , Humanos , Imunidade Inata , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/administração & dosagem , Injeções Intravenosas , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Células THP-1 , Fator de Necrose Tumoral alfa/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismo
7.
Adv Clin Chem ; 91: 1-29, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31331486

RESUMO

Celiac disease (CD) is a T cell-mediated inflammatory autoimmune disorder of the upper small intestine caused by the ingestion of gluten. It is increasingly recognized as a global problem by experts and societies. The diagnosis of CD is of crucial importance because its delay strongly affects patient's health and quality of life. The diagnosis of CD is, however, complex and requires reliable, sensitive, specific, rapid, simple, and cost-effective, as well-as non-invasive analytical tools. There is also a high demand to develop simple point-of-care (POC) tests for non-specialists at home or in doctors' offices. Analytical techniques are now moving toward the development of fast, more simple, non-invasive, and POC analyses. The present review focuses on recent advances of CD biomarker detection in body fluids, concerning CD specific autoantibody detection in blood and saliva using electrochemical, optic-fiber, and piezoelectric biosensors and POC finger-prick tests, and identifying CD characteristic volatile organic compounds (VOCs) in urine and feces.


Assuntos
Anticorpos/sangue , Linfócitos T CD4-Positivos/fisiologia , Doença Celíaca/diagnóstico , Técnicas Biossensoriais , Técnicas Eletroquímicas , Humanos
8.
Gastroenterology ; 157(4): 985-996.e2, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31194979

RESUMO

BACKGROUND & AIMS: Proactive monitoring of drug trough concentrations and antibodies against drugs might help determine whether patients are likely to respond to treatment and increase efficacy. We investigated whether proactive drug monitoring is associated with higher rates of clinical remission in pediatric patients with Crohn's disease (CD). METHODS: We performed a nonblinded, randomized controlled trial of 78 children with CD (6-18 years old; 29% female; mean age, 14.3 ± 2.6 years) who had not received prior treatment with a biologic agent but had responded to adalimumab induction therapy, under scheduled monitoring of clinical and biologic measures (based on clinical factors and levels of C-reactive protein and fecal calprotectin), at pediatric gastroenterology units in Israel from July 2015 through December 2018. The patients were randomly assigned to groups that received proactive monitoring (trough concentrations measured at weeks 4 and 8 and then every 8 weeks until week 72, n = 38) or reactive monitoring (physicians were informed of trough concentrations after loss of response, n = 40). In both groups, doses and intervals of adalimumab were adjusted to achieve trough concentrations of 5 µg/mL. The primary endpoint was sustained corticosteroid-free clinical remission at all visits (week 8 through week 72). RESULTS: The primary endpoint was achieved by 31 children (82%) in the proactive group and 19 children (48%) in the reactive group (P = .002). Sixteen patients in the proactive monitoring group (42%) achieved a composite outcome of sustained corticosteroid-free remission, C-reactive protein ≤0.5 mg/dL, and level of fecal calprotectin ≤150 µg/g compared with 5 patients in the reactive monitoring group (12%) (P = .003). By week 72 of treatment, 33 patients in the proactive monitoring group had received adalimumab intensification (87%) compared with 24 patients in the reactive monitoring group (60%) (P = .001). CONCLUSIONS: In a randomized controlled trial of pediatric patients with CD, we found that proactive monitoring of adalimumab trough concentrations and adjustment of doses and intervals resulted in significantly higher rates corticosteroid-free clinical remission than reactive monitoring (measuring trough concentration after loss of response). Clinicaltrials.gov no.: NCT02256462.


Assuntos
Adalimumab/sangue , Adalimumab/uso terapêutico , Anti-Inflamatórios/sangue , Anti-Inflamatórios/uso terapêutico , Anticorpos/sangue , Doença de Crohn/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Fármacos Gastrointestinais/sangue , Fármacos Gastrointestinais/uso terapêutico , Adalimumab/imunologia , Adalimumab/farmacocinética , Adolescente , Corticosteroides/uso terapêutico , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/farmacocinética , Biomarcadores/sangue , Criança , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Doença de Crohn/imunologia , Feminino , Fármacos Gastrointestinais/imunologia , Fármacos Gastrointestinais/farmacocinética , Humanos , Israel , Masculino , Modelos Biológicos , Valor Preditivo dos Testes , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento
9.
J Vet Sci ; 20(3): e30, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31161748

RESUMO

Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus and anti-GnRH antibodies are not formed under normal conditions. However, administration an excess of recombinant GnRH protein results in the formation of anti-GnRH. We evaluated the efficacy of the recombinant Salmonella typhimurium flagellin fljB (STF2)-GnRH vaccine in inducing infertility in 17 intact male cats. The first vaccination and a boosting vaccine was injected for examination. Serum was obtained from blood collected at monthly intervals and anti-GnRH antibodies and testosterone concentrations were determined. Six months after the vaccination, testicular samples are obtained and used for histological examination. Compared with sham control group, the injection groups showed an increase in anti-GnRH antibody titers and testosterone concentrations tended to be reduced in the injection groups and increased in the control group. Histological evaluations and Johnsen's testicular biopsy scores revealed testicular hypoplasia in the 2 injection groups. Consequently, normal sexual maturation with sperm production was observed in the control group. In contrast, the cats that received the GnRH vaccine showed weak (2 of 7 cats) or moderate (4 out of 7 cats) dose-dependent infertility effects. On the basis of the results, the STF2-GnRH vaccine was identified to be effective in inducing infertility in male cats. The results of this study thus indicate the possibility of immunological castration targeting feral cats.


Assuntos
Flagelina/imunologia , Hormônio Liberador de Gonadotropina/imunologia , Infertilidade Masculina/induzido quimicamente , Orquiectomia/veterinária , Maturidade Sexual/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Vacinas Anticoncepcionais/normas , Animais , Anticorpos/sangue , Gatos , Escherichia coli/genética , Flagelina/genética , Hormônio Liberador de Gonadotropina/genética , Masculino , Orquiectomia/métodos , Proteínas Recombinantes/farmacologia , Testículo/efeitos dos fármacos , Testosterona/sangue , Vacinas Anticoncepcionais/farmacologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/farmacologia
10.
BMC Med Genet ; 20(1): 114, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242861

RESUMO

BACKGROUND: Dedicator of cytokinesis 8 (DOCK8) deficiency (MIM #243700) is a rare disease, leads to a combined primary immunodeficiency (PID), and accounts for the autosomal recessive-hyper immunoglobulin E syndrome (AR-HIES). DOCK8 deficiency status characterizes by recurrent infections, atopy, and risk of cancer. Lymphoproliferative disease complicating PID, is difficult to diagnose. Our aim is to present a rare case of PID, and to the best of our knowledge, she is the first case of DOCK8 deficiency from Iraq. The genetic diagnosis was carried out in Japan using dried blood spot-based DNA transfer and whole-exome sequencing. CASE PRESENTATION: An 11-year-old Iraqi girl, of double first-cousin-parents, had a history of severe eczema, food allergy, and repeated infections. She presented with a jaw mass, bilateral cervical and axillary lymphadenopathy, and immunoglobulin (Ig) assays of 20, 3.3 and 1.7-fold above maximum normal level for age of IgE, IgA and IgG, respectively, along with a low IgM, eosinophilia and lymphopenia. Based on the jaw mass biopsy, non-Hodgkin lymphoma was suggested in Iraq, whereas histopathological re-evaluation in Japan revealed the diagnosis of a polyclonal reactive proliferation spectrum of lymphoproliferative disorders/plasmacytic hyperplasia, complicating PID. Whole-exome sequencing supported the diagnosis of PID by identifying a homozygous DOCK8 mutation with previously reported pathogenicity (NM_203447:c.3332delT, p.Phe1113Leufs*2), that may be attributed to consanguinity. CONCLUSIONS: International collaboration using an effective DNA transportation technique and next-generation sequencing was the key to pinpoint the diagnosis of DOCK8 deficiency. Our case asserted that careful pathogenetic evaluation, in an advanced setting, was crucial for ruling out the neoplastic process. Pediatricians in areas with a high prevalence of consanguinity marriage should have a high index of suspicion of DOCK8 deficiency in patients with recalcitrant eczema, and frequent respiratory and skin infectious episodes.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Fatores de Troca do Nucleotídeo Guanina/genética , Síndrome de Job/genética , Mutação , Sequenciamento Completo do Exoma/métodos , Anticorpos/sangue , Criança , Consanguinidade , DNA/sangue , Eosinofilia/imunologia , Feminino , Homozigoto , Humanos , Iraque , Japão , Arcada Osseodentária/patologia , Síndrome de Job/diagnóstico por imagem , Síndrome de Job/imunologia , Síndrome de Job/patologia , Linfopenia/imunologia , Transtornos Linfoproliferativos/genética , Linhagem
11.
Scand J Rheumatol ; 48(5): 362-366, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31244356

RESUMO

Objective: Infliximab-treated patients with rheumatoid arthritis (RA) may respond insufficiently due to low serum infliximab (sIFX) levels, caused by anti-drug antibodies (ADAs). However, monitoring of sIFX and ADAs is not routinely implemented, and levels for optimal outcome have not been validated. We searched for predictors for sIFX < 0.2 µg/mL and ADA development in a randomized setting. Methods: In the SWEFOT trial, of 128 patients randomized to methotrexate + IFX therapy, 101 had serum samples at 3, 9, and 21 months that were analysed for sIFX [enzyme-linked immunosorbent assay (ELISA)] and ADAs [ELISA, and precipitation and acid dissociation (PandA) when sIFX > 0.2 µg/mL]. The primary and secondary outcome measures were low disease activity [LDA = 28-joint Disease Activity Score (DAS28) ≤ 3.2] and remission (DAS28 < 2.6). Baseline characteristics were assessed as potential predictors of sIFX < 0.2 µg/mL or ADA positivity, using logistic regression. Results: Categorization of sIFX levels into < 0.2, 0.2-2.9, 3.0-7.0, and > 7.0 µg/mL showed a dose-response association with LDA (30%, 64%, 67%, and 79%, respectively, p = 0.008) and remission (10%, 45%, 39%, and 66%, p = 0.004) at trial cessation (21 months). Female patients had sIFX < 0.2 µg/mL more often than males (35% vs 7%, p = 0.006), with a similar trend for rheumatoid factor (RF)-positive vs RF-negative patients (34% vs 16%, p = 0.059). ADA positivity showed similar patterns, also after adjustment for potential confounders (female sex: p = 0.050; RF positivity: p = 0.067). PandA captured four highly ADA-reactive patients with sIFX > 0.2 µg/mL, of whom three were ADA positive at other time-points, all with high DAS28 at follow-up. Conclusion: In early RA patients receiving IFX as a second-line agent, sIFX < 0.2 µg/mL and ADA development were associated with treatment failure and were more common in females, with a similar trend for RF positivity. Our findings support the use of therapeutic drug monitoring, and PandA in ADA-negative non-responders. Trial registration: SWEFOT NCT00764725 ( https://clinicaltrials.gov/ct2/show/NCT00764725 ).


Assuntos
Anticorpos/sangue , Artrite Reumatoide/tratamento farmacológico , Infliximab/farmacocinética , Fator Reumatoide/sangue , Anticorpos/imunologia , Antirreumáticos/imunologia , Antirreumáticos/farmacocinética , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Infliximab/imunologia , Masculino , Metotrexato/uso terapêutico , Falha de Tratamento
12.
Microb Pathog ; 135: 103613, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31254602

RESUMO

Avian influenza viruses (AIVs) in wild birds pose a pandemic threat to humans and to the poultry industry. To assess AIV and AIV antibody prevalence in wild birds in China, a systematic review and meta-analysis were conducted. We searched PubMed, Google Scholar, Cochrane Library, Clinical Trial, VIP, CNKI, and WANFANG for published papers related to the prevalence of AIVs and their associated antibodies in wild birds in China from Mar. 10, 2005 to Sept. 20, 2018. Repeat studies, reviews, and other host studies were excluded, as well as those with inconsistent data, incomplete information, or only prevalence data or data from outside of mainland China. In total, data from 28 publications were compiled and analyzed. Based on out meta-analysis, the pooled prevalence of AIVs in wild birds in China was found to be 2.5% (571/23,024), and the pooled prevalence of AIV antibodies was 26.5% (1,210/4,566). The pooled prevalence of AIVs was significantly higher in wild birds from Central China (5.5%, 271/4, 955) compared to all other regions and the pooled prevalence of AIV antibodies was significantly in wild birds from South China (56.8%, 92/162) in comparison to all other regions. The prevalence of both AIVs and AIV antibodies in Anseriformes were higher compared to non-Anseriformes. In addition, the largest number of studies found in this review were on the HA subtypes of AIVs (H5, H7, and H9) and their associated antibodies. In summary, our findings suggest that the prevalence of AIVs and their antibodies in wild birds vary among regions and species of wild bird. Thus, further monitoring of the prevalence of AIVs and their antibodies in wild birds in China is necessary and should be used for guiding powerful and effective regulatory measures that will prevent the spread of AIVs across species.


Assuntos
Animais Selvagens/virologia , Anticorpos/sangue , Aves/virologia , Vírus da Influenza A , Influenza Aviária/epidemiologia , Influenza Aviária/imunologia , Animais , China/epidemiologia , Bases de Dados Factuais , Pandemias , Prevalência
13.
BMC Infect Dis ; 19(1): 543, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221089

RESUMO

BACKGROUND: Cysticercosis is an emerging and neglected tropical disease (NTD) that poses a serious public health concern worldwide. Disseminated cysticercosis (DCC) is an uncommon manifestation of cysticercosis, also found in China. CASE PRESENTATION: We report three cases of DCC in patients living in China, with different clinical and radiological presentations. All three patients had DCC with active ocular cysticercosis, including one patient with widespread DCC caused by direct ingestion of Taenia solium eggs. The intravitreal cysticercus cyst in this patient was completely extracted entirely by 23-gauge pars plana vitrectomy, and the cyst was oval in shape on the flat mount preparation. CONCLUSION: The clinical presentation of DCC is highly sophisticated. The diagnosis depended on the typical radiological presentations, biopsy and flat mount preparations of the cyst.


Assuntos
Cisticercose/diagnóstico , Adolescente , Adulto , Albendazol/uso terapêutico , Animais , Anticorpos/sangue , Anticorpos/líquido cefalorraquidiano , Antiprotozoários/uso terapêutico , Encéfalo/diagnóstico por imagem , Cisticercose/tratamento farmacológico , Cisticercose/parasitologia , Feminino , Humanos , Larva/fisiologia , Imagem por Ressonância Magnética , Masculino , Taenia solium/crescimento & desenvolvimento , Taenia solium/isolamento & purificação , Vitrectomia , Adulto Jovem
14.
Vet Immunol Immunopathol ; 211: 38-43, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31084892

RESUMO

Natural antibodies (NAb) are antibodies that can bind to a particular antigen without any apparent antigenic stimulation. In this paper, a careful analysis has been carried out on NAb levels in goat kid serum; possible correlations with the total immunoglobulin (tot-Ig) levels and specific antibody (SpAb) response were considered. Twenty randomly chosen kids were submitted to a first blood sampling (day 0). After 60 and 100 days, new blood samplings were carried out in the same animals. On day 0, after blood collection, all animals were immunized with a commercial vaccine; the immunization was repeated 30 days apart. Some exogenous antigens were tested to verify their immunoreactivity to NAb. Among them, the synthetic hapten 2,4,6-trinitrophenyl (TNP) conjugated with bovine serum albumin, resulted as the antigen with the higher immunoreactivity to NAb. Tot-Ig levels increased over time (p < 0.001). On the contrary, NAb levels, both IgG- and IgM-isotypes, significantly decreased during the experimental period (p < 0.001 and <0.05, respectively). Linear regression analyses showed a high correlation between IgM-NAb and tot-IgM levels (p < 0.001) at all the evaluated sampling times. However, a significant correlation between IgG-NAb and IgM-NAb was found only at the 1st (p < 0.01) and at the 2nd sampling (p < 0.05). No significant correlations were found between SpAb response and the other assessed humoral immune parameters. The obtained results are discussed in the light of the possible use of NAb assessment for the evaluation of the immune system activity in goat.


Assuntos
Imunidade Adaptativa/imunologia , Anticorpos/imunologia , Cabras/imunologia , Imunoglobulinas/imunologia , Animais , Anticorpos/sangue , Formação de Anticorpos/imunologia , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Cabras/sangue , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Imunoglobulinas/sangue , Masculino
16.
Afr J Prim Health Care Fam Med ; 11(1): e1-e5, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31038347

RESUMO

BACKGROUND: An allergic reaction to mammalian meat has recently been reported in rural parts of South Africa and throughout other parts of the world. The cause of this allergic reaction is because of an oligosaccharide antigen known as galactose-alpha-1, 3-galactose (alpha-gal) found in mammalian meat. Hard ticks in various parts of the world have been identified as a cause of sensitisation to the alpha-gal antigen. However, mechanisms of sensitisation in Africa are poorly understood. AIM: The aim of this article is to review current literature on the alpha-gal allergy and mammalian meat ingestion and the family physician's role in diagnosing and managing this condition. METHOD: Indexes were searched using the keywords in the following electronic databases: Elsevier Science Direct, Google Scholar, Medline and PubMed. RESULTS: Clinical presentation of the alpha-gal allergy occurs typically as a delayed anaphylaxis occurring within 3-6 hours after the ingestion of mammalian meat. A subset of patients described in South Africa presented with a rapid onset of symptoms occurring within 45 minutes. Furthermore, some of these patients present with abdominal symptoms only, which may be mistaken as food poisoning. Diagnosis is based on a history of reaction to mammalian meats (especially to fatty portions or organs) and serum specific alpha-gal antibodies. The main management of the alpha-gal allergy is avoidance of red meat and in mild reactions treatment with oral H1 receptor antihistamines. CONCLUSION: Sensitisation to the alpha-gal allergy results in adverse reactions to red meat, with tolerance to turkey, chicken and fish. A family physician can safely manage this condition.


Assuntos
Dissacarídeos/imunologia , Hipersensibilidade Alimentar/diagnóstico , Carne/efeitos adversos , Papel do Médico , Atenção Primária à Saúde/métodos , Animais , Anticorpos/sangue , Anticorpos/imunologia , Gerenciamento Clínico , Hipersensibilidade Alimentar/imunologia , Humanos , Mamíferos , Carne/análise , África do Sul
17.
Arch Endocrinol Metab ; 63(4): 351-357, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31038589

RESUMO

OBJECTIVE: In this study, we aimed to describe the prevalence and distribution of positive antithyroperoxidase antibodies (TPOAb) according to sex, age strata, and presence of thyroid dysfunction using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). MATERIALS AND METHODS: Thyroid hormone tests were obtained from each study participant at baseline. Levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured using a third-generation immunoenzymatic assay. Antithyroperoxidase antibodies were measured by electrochemiluminescence and were considered to be positive when ≥ 34 IU/mL. RESULTS: The prevalence of TPOAb among 13,503 study participants was 12%. Of participants with positive TPOAb, 69% were women. Almost 60% of the individuals with positive TPOAb were white. The presence of positive TPOAb was associated with the entire spectrum of thyroid diseases among women, but only with overt hyperthyroidism and overt hypothyroidism in men. CONCLUSION: The distribution of positive TPOAb across sex, race, age, and thyroid function in the ELSA-Brasil study is aligned with the worldwide prevalence of positive TPOAb reported in iodine-sufficient areas. In women, the presence of TPOAb was related to the entire spectrum of thyroid dysfunction, while in men, it was only related to the occurrence of overt thyroid disease.


Assuntos
Anticorpos/sangue , Iodeto Peroxidase/sangue , Doenças da Glândula Tireoide/epidemiologia , Adulto , Distribuição por Idade , Idoso , Índice de Massa Corporal , Brasil/epidemiologia , Brasil/etnologia , Estudos Transversais , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por Sexo , Doenças da Glândula Tireoide/sangue , Tireotropina/sangue , Tiroxina/sangue
18.
Adv Respir Med ; 87(2): 83-89, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038718

RESUMO

INTRODUCTION: Hypersensitivity pneumonitis (HP) is the third most common interstitial lung disease after idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Pathogenesis of HP is related to repeated exposure to inhaled environmental antigens that sensitise the susceptible, genetically predisposed persons. The aim of the present retrospective study was to summarise the diagnostic methods used in consecutive patients with HP, recognised in a single pulmonary unit, between 2005 and 2015, and to compare them with current diagnostic criteria. MATERIAL AND METHODS: 135 patients, 68 males, 67 females, median age 53 years (18-75 years), entered the study. Chest CT features characteristic of HP were defined as: mosaic attenuation of lung parenchyma, air trapping and/or ill-defined centrilobular nodules. Lymphocytosis in BAL was defined as ≥ 30%. RESULTS: Median time from first symptoms to diagnosis was 12 months. The exposure to one or more allergens was found in 94% of patients, chest CT features characteristic of HP have been reported in 87%, BAL lymphocytosis - in 86%. According to recent diagnostic criteria - in 54% of patients, clinical diagnosis of HP was confident, in 16% - probable, in 26% - possible and in 4% - unlikely. The confirmation of HP with lung biopsy has been obtained in 36% of non-confident cases (16% of the study group). CONCLUSION: HP diagnosis was confirmed according to current diagnostic criteria in 70% of patients diagnosed between 2005 and 2015. Contradictions to lung biopsy have been the main reason for inability to confirm HP in non-confident cases.


Assuntos
Alveolite Alérgica Extrínseca/diagnóstico , Alvéolos Pulmonares/diagnóstico por imagem , Adulto , Idoso , Alveolite Alérgica Extrínseca/diagnóstico por imagem , Alveolite Alérgica Extrínseca/terapia , Anticorpos/sangue , Biomarcadores/sangue , Líquido da Lavagem Broncoalveolar , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Masculino , Pessoa de Meia-Idade , Alvéolos Pulmonares/patologia , Testes de Função Respiratória , Estudos Retrospectivos
19.
PLoS One ; 14(5): e0217163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116766

RESUMO

Understanding the immunological phenotype of transplant recipients is important to improve outcomes and develop new therapies. Immunophenotyping of whole peripheral blood (WPB) by flow cytometry is a rapid method to obtain large amounts of data relating to the outcomes of different transplant treatments with limited patient impact. Healthy individuals and patients with type 1 diabetes (T1D) enrolled in islet transplantation were recruited and WPB was collected. 46 fluorochrome-conjugated mouse-anti-human antibodies were used (43 of 46 antibodies were titrated). BD cytometer setup and tracking beads were used to characterize and adjust for cytometer performance. Antibody cocktails were pre-mixed <60 minutes before staining. Multicolour panels were designed based on fluorochrome brightness, antigen density, co-expression, and fluorochrome spillover into non-primary detectors in each panel on a 5 laser flow cytometer. WPB sample staining used 50-300 µl WPB for each panel and was performed within 2 hours of blood sample collection. Samples were acquired on a BD-LSRFortessa. The operating procedures, including specimen collection, antibody cocktails, staining protocol, flow-cytometer setup and data analysis, were standardized. The staining index of 43 antibodies and the spillover spreading matrix for each panel was calculated. The final concentrations for the 46 antibodies used was determined for staining of WPB samples. Absolute cell-count and 7 leukocyte profiling panels consisting of subsets and/or status of granulocytes, monocytes, dendritic, B, NK, and T cells including regulatory T cells (Tregs) and NKT were designed and established on a 5 laser BD-LSR Fortessa. 13 T1D patients, including 4 islet transplant recipients and 8 healthy controls, were evaluated. The ability to reproducibly measure immune subsets and immune-profiles of islet transplant patients up to 18 months post transplantation has been established as a tool to measure immune cell reconstitution after transplantation.


Assuntos
Anticorpos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/terapia , Citometria de Fluxo/normas , Imunofenotipagem/métodos , Transplante das Ilhotas Pancreáticas/métodos , Transplantados/estatística & dados numéricos , Anticorpos/sangue , Estudos de Casos e Controles , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 1/sangue , Humanos
20.
PLoS Negl Trop Dis ; 13(4): e0007048, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31002673

RESUMO

BACKGROUND: The hyaluronidase enzyme is generally known as a spreading factor in animal venoms. Although its activity has been demonstrated in several organisms, a deeper knowledge about hyaluronidase and the venom spreading process from the bite/sting site until its elimination from the victim's body is still in need. Herein, we further pursued the goal of demonstrating the effects of inhibition of T. serrulatus venom (TsV) hyaluronidase on venom biodistribution. METHODS AND PRINCIPAL FINDINGS: We used technetium-99m radiolabeled Tityus serrulatus venom (99mTc-TsV) to evaluate the venom distribution kinetics in mice. To understand the hyaluronidase's role in the venom's biodistribution, 99mTc-TsV was immunoneutralized with specific anti-T.serrulatus hyaluronidase serum. Venom biodistribution was monitored by scintigraphic images of treated animals and by measuring radioactivity levels in tissues as heart, liver, lungs, spleen, thyroid, and kidneys. In general, results revealed that hyaluronidase inhibition delays venom components distribution, when compared to the non-neutralized 99mTc-TsV control group. Scintigraphic images showed that the majority of the immunoneutralized venom is retained at the injection site, whereas non-treated venom is quickly biodistributed throughout the animal's body. At the first 30 min, concentration peaks are observed in the heart, liver, lungs, spleen, and thyroid, which gradually decreases over time. On the other hand, immunoneutralized 99mTc-TsV takes 240 min to reach high concentrations in the organs. A higher concentration of immunoneutralized 99mTc-TsV was observed in the kidneys in comparison with the non-treated venom. Further, in situ neutralization of 99mTc-TsV by anti-T.serrulatus hyaluronidase serum at zero, ten, and 30 min post venom injection showed that late inhibition of hyaluronidase can still affect venom biodistribution. In this assay, immunoneutralized 99mTc-TsV was accumulated in the bloodstream until 120 or 240 min after TsV injection, depending on anti-hyaluronidase administration time. Altogether, our data show that immunoneutralization of hyaluronidase prevents venom spreading from the injection site. CONCLUSIONS: By comparing TsV biodistribution in the absence or presence of anti-hyaluronidase serum, the results obtained in the present work show that hyaluronidase has a key role not only in the venom spreading from the inoculation point to the bloodstream, but also in venom biodistribution from the bloodstream to target organs. Our findings demonstrate that hyaluronidase is indeed an important spreading factor of TsV and its inhibition can be used as a novel first-aid strategy in envenoming.


Assuntos
Antivenenos/farmacologia , Hialuronoglucosaminidase/antagonistas & inibidores , Rim/metabolismo , Venenos de Escorpião/farmacocinética , Escorpiões , Animais , Anticorpos/sangue , Feminino , Camundongos , Especificidade de Órgãos , Cintilografia , Tecnécio , Distribuição Tecidual
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