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1.
Tuberculosis (Edinb) ; 111: 102-108, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30029893

RESUMO

BACKGROUND: QuantiFERON (QFT) results near the cut-off are subject to debate. We aimed to investigate which borderline QFT results were due to Mycobacterium tuberculosis (Mtb)-specific responses or to test variability. METHODS: In a contact investigation, tuberculin skin test (TST), QFT and T-SPOT.TB (T-SPOT) were performed in 785 BCG-unvaccinated contacts. Contacts with a low-negative (<0.15), borderline (0.15-0.35), low-positive (0.35-0.70) or high-positive QFT (≥0.70 IU/mL) were compared with respect to exposure, TST and T-SPOT results. Development of active tuberculosis was assessed. RESULTS: Borderline QFT results occurred in threefold excess over test variability (p = 0.0027). In contacts with low-negative, borderline or positive QFT results, a positive TST occurred in 24.9%, 62.1% and 91.4% (p < 0.0001) and a positive T-SPOT result in 6.3%, 41.3% and 86.4%, respectively (p < 0.0001). Two-third (20/29) of contacts with a borderline and 14/16 (88%) with a low-positive QFT had a positive TST and/or T-SPOT, indicating probable Mtb-infection. During 12 years of follow-up, seven patients were diagnosed with active tuberculosis, two of whom after a low-positive QFT. CONCLUSIONS: In this study, most borderline and low-positive QFT results were Mtb-specific, showing the biological significance of a borderline QFT. The clinical relevance, however, will be most distinct in patients who are or will be immunocompromised.


Assuntos
ELISPOT , Testes de Liberação de Interferon-gama , Interferon gama/sangue , Tuberculose Latente/diagnóstico , Mycobacterium tuberculosis/imunologia , Tuberculose/diagnóstico , Adolescente , Biomarcadores/sangue , Feminino , Interações Hospedeiro-Patógeno , Humanos , Interferon gama/imunologia , Tuberculose Latente/sangue , Tuberculose Latente/imunologia , Tuberculose Latente/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/patogenicidade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo , Teste Tuberculínico , Tuberculose/sangue , Tuberculose/imunologia , Tuberculose/microbiologia , Adulto Jovem
2.
PLoS One ; 10(9): e0137196, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26339905

RESUMO

OBJECTIVE: To investigate the association of farm exposure and the development of ANCA-associated vasculitis (AAV). METHODS: One hundred eighty-nine well defined patients with AAV (n = 119 with granulomatosis with polyangiitis [GPA], n = 48 with microscopic polyangiitis [MPA], n = 22 patients with eosinophilic granulomatosis with polyangiitis [EGPA]) and 190 controls (n = 119 patients with rheumatoid arthritis, n = 71 with large vessel vasculitis) were interrogated using a structured questionnaire. Factors investigated were occupation, farm exposure, contact to different livestock, participation in harvesting, residence next to a farm, MRSA status, and contact to domestic pets at disease onset or ever before. The odds ratio (OR) and 95% confidence interval [95%CI] were calculated for each item. RESULTS: Univariate analysis revealed a strong association of AAV with regular farm exposure; OR 3.44 [95%CI 1.43-8.27]. AAV was also associated with regular contact to cattle 4.30 (1.43-8.27), pigs 2.75 (1.12-6.75) and MRSA carriage 3.38 (1.11-10.3). This association was stronger in the subgroup of GPA patients. OR in this group for farm exposure was 4.97; [2.02-12.2], for cattle 6.71 [95% CI 2.19-20.7], for pigs 4.34 [1.75-10.9], and MRSA carriage 5.06 [1.62-15.8]). There was no significant association of MPA or EGPA with these parameters. CONCLUSION: A significant association between farm exposure or farm animal exposure and AAV especially in the subgroup of patients with GPA has been identified. This suggests that these entities are distinct and have different triggers for the immune process.


Assuntos
Criação de Animais Domésticos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/etiologia , Síndrome de Churg-Strauss/etiologia , Granulomatose com Poliangiite/etiologia , Exposição Ocupacional/efeitos adversos , Adulto , Idoso , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Estudos de Casos e Controles , Bovinos , Síndrome de Churg-Strauss/sangue , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/imunologia , Feminino , Granulomatose com Poliangiite/sangue , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/imunologia , Humanos , Masculino , Poliangiite Microscópica/sangue , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/imunologia , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Inquéritos e Questionários , Suínos
3.
Scand J Rheumatol ; 44(4): 302-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25744854

RESUMO

OBJECTIVES: To determine whether platelet (PLT) counts might serve as a biomarker to distinguish between active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission and also between active disease and systemic infection. METHOD: PLTs were analysed before treatment in patients with AAV in the active state and in remission. PLTs were also analysed in AAV patients with acute infections. The results were correlated with clinical manifestations, the Birmingham Vasculitis Activity Score version 3 [BVAS(v.3)], and other laboratory findings [i.e. C-reactive protein (CRP), leucocytes, differential count, procalcitonin (PCT)]. Diagnostic accuracy was calculated with a receiver operating characteristic (ROC) curve. RESULTS: PLT counts were significantly increased in 98 patients with AAV during the active disease state [median: 405 PLTs/nL; interquartile range (IQR) 288-504] compared to patients in remission (246 PLT/nL; IQR 214-289) (p < 0.001). We found a correlation of PLT counts in active disease with the BVAS(v.3) (r = 0.582, p < 0.001). In AAV patients with systemic infections (n = 37), PLT counts exhibited significantly lower values (226 PLT/nL; IQR 163-273) compared to patients with active disease (p < 0.001). In the ROC curve analysis, the area under the curve (AUC) of PLTs was significantly larger when distinguishing active disease from systemic infection (AUC 0.868) compared to leucocytes (AUC 0.590), CRP (AUC 0.522), or procalcitonin (AUC 0.515) (p < 0.001). CONCLUSIONS: PLT counts were found to correlate with disease activity in AAV and thus may be used to represent immunological activity. In addition, PLT counts serve as a marker that can distinguish acute infection from active disease.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Plaquetas/patologia , Contagem de Plaquetas , Índice de Gravidade de Doença , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Peptídeo Relacionado com Gene de Calcitonina , Diagnóstico Diferencial , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Precursores de Proteínas/sangue , Indução de Remissão
4.
Z Rheumatol ; 73(5): 465-6, 468, 2014 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-24659095

RESUMO

Felty's syndrome is a rare variant of severe seropositive rheumatoid arthritis with neutropenia and splenomegaly. It is difficult to treat and associated with a poor prognosis due to the substantial risk of infections. This article presents the case of a patient with refractory disease who responded to rituximab with permanent normalization of neutrophil counts. Repeated infusions were necessary to induce and maintain remission.


Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Síndrome de Felty/diagnóstico , Síndrome de Felty/tratamento farmacológico , Neutropenia/diagnóstico , Neutropenia/tratamento farmacológico , Esplenomegalia/diagnóstico , Esplenomegalia/tratamento farmacológico , Idoso , Antirreumáticos/administração & dosagem , Humanos , Fatores Imunológicos/administração & dosagem , Masculino , Rituximab , Resultado do Tratamento
5.
Lupus ; 23(4): 378-85, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24536045

RESUMO

OBJECTIVES: Associations of interleukin-10 (IL-10) promoter single nucleotide polymorphisms (SNPs) and their haplotypes with systemic lupus erythematosus (SLE) are unclear. We extended the analysis of established proximal IL-10 promoter haplotypes to a more distal SNP with functional capacity. METHODS: Two hundred and ten German caucasian SLE patients fulfilling the ACR criteria and 160 ethnically, age and sex matched controls were genotyped for IL-10 -2849 G > A, -1082 A > G, -819 T > C and -592 C > A. Haplotypes were reconstructed via a mathematical model, then allele and haplotype distributions were compared between patients and controls and patients with different disease manifestations. RESULTS: We detected at -2849, -1082, -819 and -592 the four predominant haplotypes GGCC (22% in patients vs. 29% in controls), AGCC (24% vs. 21%), GACC (30% vs. 25%) and GATA (24% vs. 24%). GGCC was underrepresented in SLE patients, suggesting a protective effect (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.48-0.94). AGCC was found significantly more frequently in patients with pathognomonic anti-dsDNA antibodies (26% vs. 15%; OR 1.98, 95% CI 1.04-3.75). As compared to patients with glomerulonephritis type V (WHO classification), the presumptive IL-10 high producer allele -2849 G was found significantly more often in patients with GN type III/IV (93% vs. 60%; OR 8.7, 95% CI 1.59-47.15). CONCLUSION: Our data confirm that the complexity of the IL-10 promoter evokes the need for a meticulous analysis of its haplotypic structure in order to specify disease associations, particularly under functional aspects, thereby shedding light on the pathophysiology of SLE.


Assuntos
Predisposição Genética para Doença , Interleucina-10/genética , Lúpus Eritematoso Sistêmico/genética , Modelos Teóricos , Alelos , Estudos de Casos e Controles , DNA/imunologia , Feminino , Genótipo , Alemanha , Haplótipos , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , População Branca/genética
6.
Med Klin Intensivmed Notfmed ; 109(2): 121-8, 2014 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-23846173

RESUMO

BACKGROUND: In elderly patients, an unspecific increase of fibrin degradation products in blood is observed. Thus, the D-dimer test to rule out thromboembolic events has a high false-positive rate in elderly patients. Our aim was to validate an age-adjusted D-dimer cut-off and to assess its utility in elderly patients. METHODS: In a retrospective cohort of outpatients (n = 1033) presenting to our emergency department with suspected acute pulmonary embolism and/or deep vein thrombosis (PE/DVT), age-adjusted D-dimer cut-off values were derived using receiver operating characteristic (ROC) curve analysis. Subsequently, the proportion of patients with normal D-dimer and false-negative test results, respectively, and the number needed-to-test (NNT) were compared for conventional and age-adjusted cut-off values. RESULTS: Using the conventional cut-off of 0.5 mg/dl, PE/DVT could be excluded in 68 % of patients, whereas the age-adjusted cut-off [(age × 0.016) mg/l] ruled out 77 % of patients. Particularly in patients > 70 years, the negative prediction accuracy of excluding a PE/DVT increased explicitly. The failure rate of the age-adjusted cut-off value was 0.8 % (95 % confidence interval 0.3-1.6 %). CONCLUSION: The age-adjusted D-dimer cut-off point increases the proportion of older patients, in whom an acute thromboembolic event can be excluded.


Assuntos
Serviço Hospitalar de Emergência , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Tromboembolia/sangue , Tromboembolia/diagnóstico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Números Necessários para Tratar , Valor Preditivo dos Testes , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnóstico , Curva ROC , Valores de Referência , Estudos Retrospectivos , Trombose Venosa/sangue , Trombose Venosa/diagnóstico
10.
Z Rheumatol ; 70(3): 232-4, 236-8, 2011 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-21359555

RESUMO

OBJECTIVES: The various biologic agents currently available for the treatment of RA can be administered subcutaneously (s.c.) or via intravenous (i.v.) infusion with variable intervals depending on the drug. This investigation aims to identify the preferences and concerns of affected patients and their physicians. METHODS: We conducted a survey of 102 patients with RA currently receiving Rituximab (RTX) therapy. They were asked about different aspects of their current and previous RA therapy, including overall satisfaction, tolerability, mode of drug administration, as well as duration and intervals. In addition, 17 rheumatologists were asked about different aspects of s.c. or i.v. drug administration, their preference and the suspected preference of their patients. RESULTS: The mean age of our patients was 59 ± 11.2 years. Patients had failed ≥2 DMARD therapies and ≥ 1 biologic treatment. The impact of RTX infusions on planning different activities including job, hobbies or travelling was considered as low or very low in 76% of the respondents. Interestingly, 63.4% of patients would prefer an infusion every 6-9 months as RA therapy, whereas 21.5% would prefer tablets only; 12.9% of our patient cohort would prefer s.c. injections every second week, and only 2% would prefer an infusion every month. In all, 92% of patients questioned would choose RTX therapy again. In contrast, 88% of rheumatologists preferred s.c. injection and even 94% of them assumed that their patients would do so as well if they had the choice. The suggested reasons included greater flexibility, convenience and independence during s.c. therapy. CONCLUSION: Contrary to the assumption of rheumatologists, we have demonstrated a preference among RTX patients for i.v. drug administration every 6-9 months over other methods of administration.


Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Atitude do Pessoal de Saúde , Preferência do Paciente/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Reumatologia/estatística & dados numéricos , Antirreumáticos/uso terapêutico , Feminino , Alemanha/epidemiologia , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Prevalência , Rituximab , Resultado do Tratamento
11.
Eur J Immunol ; 40(8): 2211-20, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20540114

RESUMO

Th1 CD4(+) T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametric flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-γ/IL-2/TNF-α triple expressors, IFN-γ/IL-2, IFN-γ/TNF-α or TNF-α/IL-2 double expressors or IFN-γ, IL-2 or TNF-α single expressors) of CD4(+) T cells in individuals with latent M. tuberculosis infection (LTBI) and active tuberculosis (TB). We found that triple expressors, while detectable in 85-90%TB patients, were only present in 10-15% of LTBI subjects. On the contrary, LTBI subjects had significantly higher (12- to 15-fold) proportions of IL-2/IFN-γ double and IFN-γ single expressors as compared with the other CD4(+) T-cell subsets. Proportions of the other double or single CD4(+) T-cell expressors did not differ between TB and LTBI subjects. These distinct IFN-γ, IL-2 and TNF-α profiles of M. tuberculosis-specific CD4(+) T cells seem to be associated with live bacterial loads, as indicated by the decrease in frequency of multifunctional T cells in TB-infected patients after completion of anti-mycobacterial therapy. Our results suggest that phenotypic and functional signatures of CD4(+) T cells may serve as immunological correlates of protection and curative host responses, and be a useful tool to monitor the efficacy of anti-mycobacterial therapy.


Assuntos
Carga Bacteriana , Linfócitos T CD4-Positivos/metabolismo , Citocinas/metabolismo , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Doença Aguda , Aciltransferases/imunologia , Adulto , Antígenos de Bactérias/imunologia , Carga Bacteriana/imunologia , Proteínas de Bactérias/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/microbiologia , Linfócitos T CD4-Positivos/patologia , Separação Celular , Doença Crônica , Citometria de Fluxo , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/patogenicidade , Tuberculose Pulmonar/diagnóstico
12.
Clin Vaccine Immunol ; 16(10): 1439-42, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19710293

RESUMO

T-SPOT.TB is a specific assay for the diagnosis of tuberculosis. The assay needs to be performed with freshly isolated cells, and interpretation requires training. T-SPOT.TB has been used in various clinical-epidemiological settings, but so far no studies have evaluated the effect of interobserver variation in test reading. Our aim was to evaluate variation between different observers in reading T-SPOT.TB results. The study was nested within an ongoing cohort study, in which part of the T-SPOT.TB had been performed with frozen material. Culture plates were read visually by four different observers from two laboratories and by two automated readers. Of 313 T-SPOT.TB assays, 235 were performed with fresh cells and 78 were performed with frozen cells. No significant difference was found between results obtained with fresh cells and those obtained with frozen cells. The percentage of positive results varied between readers by maximally 15%; five/six raters were within a 6% difference in positive results. Analysis of the observed interrater differences showed that some individuals systematically counted more spots than others did. Because test interpretation includes subtraction of background values, this systematic variance had little influence on interindividual differences. The test result as positive or negative varied between independent raters, mainly due to samples with values around the cutoff. This warrants further study regarding determinants affecting the reading of T-SPOT.TB.


Assuntos
Imunoensaio/métodos , Tuberculose/diagnóstico , Tuberculose/imunologia , Antígenos de Bactérias/administração & dosagem , Estudos de Coortes , Humanos , Imunoensaio/estatística & dados numéricos , Técnicas In Vitro , Interferon gama/biossíntese , Laboratórios , Leucócitos Mononucleares/imunologia , Mycobacterium tuberculosis/imunologia , Países Baixos , Variações Dependentes do Observador , Valor Preditivo dos Testes
13.
Z Rheumatol ; 68(2): 154-6, 2009 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-19156432

RESUMO

Leg ulcers may result in serious morbidity in patients with connective tissue diseases and Raynaud's phenomenon (RP). We describe a 35-year-old woman with mixed connective tissue disease who suffered from leg ulcers refractory to iloprost. When the patient was treated with the selective endothelin A receptor antagonist sitaxsentan for pulmonary arterial hypertension, the ulcers improved within 4 weeks and resolved completely thereafter. In addition, severity of RP ameliorated markedly. Further evaluation of sitaxsentan in patients with connective tissue diseases suffering from ischemic skin ulcers is required.


Assuntos
Isoxazóis/administração & dosagem , Úlcera da Perna/complicações , Úlcera da Perna/tratamento farmacológico , Doença de Raynaud/complicações , Doença de Raynaud/tratamento farmacológico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Tiofenos/administração & dosagem , Adulto , Anti-Hipertensivos/administração & dosagem , Feminino , Humanos , Resultado do Tratamento
15.
Scand J Rheumatol ; 37(4): 293-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18612930

RESUMO

OBJECTIVE: To determine the impact of a broad spectrum of different polymorphisms within the interleukin-10 (IL-10) promoter gene on disease susceptibility to primary Sjogren's syndrome (pSS), clinical manifestations, and autoantibody production. METHODS: We genotyped 111 unrelated German Caucasian patients with pSS and 145 healthy controls for the single nucleotide polymorphisms (SNPs) at positions -2849, -2776, -2769, -2763, -1349, -1082, -851, -819, -657, and -592 and for the microsatellites IL10.R and IL10.G. Allele and haplotype distributions were compared between patients and controls and between subgroups of patients with different clinical and laboratory findings. RESULTS: We found no significant differences in the allele or haplotype frequencies between pSS patients and healthy controls. After Bonferroni correction we found a significant association of the ACC haplotype (at the -1082, -819, and -592 loci) with immunoglobulin (Ig)A antibodies to anti-alpha-fodrin. CONCLUSION: Overall we found no associations of IL-10 promoter polymorphisms with the susceptibility to pSS in our cohort. The finding that the production of IgA anti-alpha-fodrin antibodies is associated with polymorphisms within the IL-10 promoter region suggests a genetic contribution to the generation of these antibodies.


Assuntos
Autoanticorpos/genética , Proteínas de Transporte/imunologia , Interleucina-10/genética , Proteínas dos Microfilamentos/imunologia , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas , Síndrome de Sjogren/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Imunoglobulina A/genética , Imunoglobulina A/imunologia , Masculino , Pessoa de Meia-Idade
16.
Tuberculosis (Edinb) ; 88(3): 249-61, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18155963

RESUMO

Limited specificity of the tuberculin skin test incited the development of in vitro assays based on Mycobacterium tuberculosis-specific antigens such as ESAT-6 that are lacking in Bacillus Calmette Guérin (BCG). In animal studies, intradermal ESAT-6 was safe and induced specific skin test responses. The aim of the study was to assess the safety of intradermal recombinant dimer ESAT-6 (rdESAT-6) compared with tuberculin and to determine the human dose. The study design was a double-blind Phase I study with intra-subject randomization to the left and right forearm, comparing 2 Tuberculin Units (TU) intradermal tuberculin (RT23) with 0.01, 0.1, 1 or 10 microg rdESAT-6 in groups of five healthy controls or treated tuberculosis (TB) patients. The risk of sensitization after skin testing was assessed in healthy volunteers. All doses were tolerated well by healthy volunteers and responses to rdESAT-6 were limited to transient redness after 24 h only at the highest dose. No sensitization was observed. Because 1 microg rdESAT-6 induced large responses with local side effects in some TB patients, the 10 microg dose of rdESAT-6 was not tested. Mean responses to 0.01, 0.1 and 1 microg rdESAT-6 measured 14.0, 19.8 and 38.8 mm of redness, respectively, and 7.0, 13.4 and 14.6 mm of induration. The response to tuberculin was similar to the responses to 0.1 microg rdESAT-6. Mild local side effects due to tuberculin and rdESAT-6 were observed in 8/15, respectively, 6/15 patients, more pronounced at the highest rdESAT-6 dose. In conclusion, this pilot Phase I study of safety, feasibility and dose finding of intradermal rdESAT-6 provides proof of principle of a specific skin test for human use. No serious adverse events were observed but the study was not sufficiently powered to demonstrate complete safety. Intradermal rdESAT-6 did not seem to sensitize healthy volunteers. In treated TB patients, responses to rdESAT-6 were optimal at 0.1 microg. Further studies are needed to evaluate sensitization after repeated doses and to study the effect of additional CFP-10 on the sensitivity of a TB-specific skin test.


Assuntos
Antígenos de Bactérias , Proteínas de Bactérias , Testes Cutâneos/métodos , Tuberculose/diagnóstico , Adulto , Idoso , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/efeitos adversos , Proteínas de Bactérias/administração & dosagem , Proteínas de Bactérias/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Variações Dependentes do Observador , Testes Cutâneos/efeitos adversos , Teste Tuberculínico/efeitos adversos , Teste Tuberculínico/métodos
17.
Clin Infect Dis ; 45(11): 1470-5, 2007 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-17990230

RESUMO

In 2005, a 24-year-old man with Crohn disease who had been treated with infliximab for several months was exposed to an individual with smear-positive tuberculosis. Soon after exposure, he complained of malaise, dry cough, and weight loss. Despite normal chest radiograph findings and negative tuberculin skin test results, tuberculosis was considered to be the most likely diagnosis. The results of a whole-blood assay for detection of interferon- gamma production in response to Mycobacterium tuberculosis-specific antigen were positive. Acid-fast staining and polymerase chain reaction of bronchoalveolar lavage fluid samples had negative results, but M. tuberculosis was cultured. After the initiation of 4 antitubercular drugs and the discontinuation of infliximab therapy, the patient developed an immune reconstitution syndrome accompanied by enlarged mediastinal lymph nodes and multiple intrapulmonary miliary lesions. This case of de novo tuberculosis during anti-tumor necrosis factor alpha treatment illustrates the uncharacteristic presentation of the disease and the elusiveness of the diagnosis, as well as the fact that discontinuation of anti-tumor necrosis factor alpha treatment can be accompanied by an immune reconstitution syndrome similar to that observed in human immunodeficiency virus-infected individuals with tuberculosis.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antituberculosos/uso terapêutico , Doença de Crohn/tratamento farmacológico , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anti-Inflamatórios/uso terapêutico , Humanos , Síndrome Inflamatória da Reconstituição Imune/induzido quimicamente , Infliximab , Masculino
18.
Clin Vaccine Immunol ; 14(9): 1203-9, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17671227

RESUMO

Cross-reactivity between Mycobacterium kansasii ESAT-6 and CFP-10 homologues and their M. bovis counterparts can confound the interpretation of immunodiagnostic tests for tuberculosis. M. kansasii is a nontuberculous mycobacterial species cultured from skin test-positive cattle in Great Britain. Using peptides derived from M. bovis and M. kansasii ESAT-6 and CFP-10 regions that differ between these species, we investigated the species specificity and cross-reactivity at the level of individual bovine T-cell epitopes. Our results demonstrated that all peptides tested are fully cross-reactive, with the exception of one ESAT-6-derived peptide that harbored an M. bovis-specific epitope(s) when it was recognized in the context of bovine leukocyte antigen (BoLA)-DQ but that was cross-reactive with its M. kansasii homologues when it was restricted by BoLA-DR. This observation further highlights that prediction of species specificity by comparing sequence identity/homology alone is not sufficient and that individuals with diverse major histocompatibility complex constellations need to be tested to characterize the cross-reactivity or species specificity of peptide-based reagents.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Epitopos de Linfócito T/imunologia , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium bovis/imunologia , Mycobacterium kansasii/imunologia , Sequência de Aminoácidos , Animais , Aves , Bovinos , Reações Cruzadas/imunologia , Dados de Sequência Molecular , Infecções por Mycobacterium não Tuberculosas/imunologia , Mycobacterium bovis/isolamento & purificação , Mycobacterium kansasii/isolamento & purificação , Especificidade da Espécie
19.
Clin Vaccine Immunol ; 14(9): 1239-41, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17626157

RESUMO

We report a follow-up study of 29 subjects with negative tuberculin skin test (TST) results in association with positive gamma interferon release assay (IGRA) results, mainly due to responses to CFP-10 in the T-SPOT.TB assay, during a contact investigation. One year later, 12/29 subjects (41%) had converted to positive TST results in association with negative IGRA results.


Assuntos
Interferon gama/imunologia , Teste Tuberculínico/métodos , Tuberculose/diagnóstico , Adulto , Idoso , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/imunologia , Humanos , Pessoa de Meia-Idade , Tuberculose/imunologia , Tuberculose/transmissão
20.
Clin Vaccine Immunol ; 14(4): 477-80, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17301213

RESUMO

The tuberculin skin test (TST) was compared with QuantiFERON-TB Gold in-tube (QFT-GIT) test for the diagnosis of tuberculosis in non-Mycobacterium bovis BCG-vaccinated military personnel. Among subjects positive by TST, 44.4% of recruits were positive by QFT-GIT compared with 11.5% subjects tested after missions abroad, suggesting that most TST conversions in the latter group were caused by nontuberculous mycobacteria.


Assuntos
Militares , Kit de Reagentes para Diagnóstico , Teste Tuberculínico , Tuberculose Pulmonar/diagnóstico , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Prospectivos
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