RESUMO
OBJECTIVE: This study aimed to establish a screening model for differentiating anti-synthetase syndrome (ASS) from other antinuclear antibody (ANA)-associated rheumatic diseases (AARD) using a combination of cytoplasmic and non-cytoplasmic ANA (ncANA) patterns. METHODS: This retrospective observational study included patients with AARDs such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SS), mixed connective tissue disease (MCTD), and polymyositis/dermatomyositis (PM/DM) who underwent ANA screening between April 2012 and December 2021. Variables included age, sex, ANA patterns (Cytoplasmic and ncANA), and titers. Logistic regression analysis of Cytoplasmic and ncANA patterns was performed to differentiate ASS from other AARDs. RESULT: The 981 diagnosed cases of AARDs consisted of SS (n = 451), SSc (n = 264), SLE (n = 201), PM/DM (n = 104), MCTD (n = 52), and ASS, including PM/DM (n = 64). Of these, 155 patients had ≥2 overlapping diseases; however, there was no overlap between AARDs and ASS. ASS is more likely to occur when the cytoplasmic titer is positive and the ncANA <320. Receiver operating characteristic (ROC) analysis of the Cytoplasmic and ncANA range revealed an area under the ROC curve (AUC) of 0.885 (95% CI: 0.844 to 0.927). CONCLUSION: It is important to detect cytoplasmic patterns as an ANA screening test for ASS diagnosis, even if the titer is low. Additionally, combining the cytoplasmic and ncANA patterns yields more accurate ASS screening results.
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The objective of the study is to develop genetic and clinical prediction models for the efficacy and hepatotoxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). Among RA patients treated with MTX, 1966 polymorphisms of 246 enzymes/transporters relevant to pharmacokinetics and pharmacodynamics were measured by the Drug Metabolism Enzymes and Transporters (DMET) microarray and direct sequencing, and clinical variables at baseline were collected. For efficacy, response criteria of the European League Against Rheumatism were used to classify patients as responders or non-responders. Hepatotoxicity was defined as elevations of aspartate aminotransferase or alanine aminotransferase ≥1.5 times the reference range upper limit. Among 166 patients, a genetic prediction model for efficacy using seven polymorphisms showed the area under the receiver operating characteristic curve (AUC) was 0.822, with 74.3% sensitivity and 76.8% specificity. A combined genetic and clinical model indicated the AUC was 0.844, with 81.5% sensitivity and 76.9% specificity. By incorporating clinical variables into the genetic model, the overall category-free net reclassification improvement (NRI) was 0.663 (P < 0.0001) and the overall integrated discrimination improvement (IDI) was 0.083 (P = 0.0009). For hepatotoxicity, a genetic prediction model using seven polymorphisms showed the AUC was 0.783 with 70.0% sensitivity and 80.0% specificity, while the combined model indicated the AUC was 0.906 with 85.1% sensitivity and 87.8% specificity (overall category-free NRI: 1.002, P < 0.0001; overall IDI: 0.254, P < 0.0001). Our genetic and clinical models demonstrated moderate diagnostic accuracy for MTX efficacy and high accuracy for hepatotoxicity. These findings should, however, be validated and interpreted with a caution until external validation.
Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Doença Hepática Induzida por Substâncias e Drogas/genética , Metotrexato/efeitos adversos , Modelos Genéticos , Idoso , Artrite Reumatoide/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Estudos de Coortes , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
A 63-year-old man presented with fever, sinusitis, otitis, and high titers of proteinase-3 anti-neutrophil cytoplasmic antibody (PR3-ANCA). Granulomatosis with polyangiitis (GPA) was first suspected. However, nasal mucosa and skin biopsies revealed the presence of intravascular large B-cell lymphoma (IVLBCL). We present a rare case of IVLBCL with a high titer of PR3-ANCA mimicking GPA.
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Anticorpos Anticitoplasma de Neutrófilos/imunologia , Granulomatose com Poliangiite/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Mieloblastina/imunologia , Diagnóstico Diferencial , Granulomatose com Poliangiite/imunologia , Humanos , Linfoma Difuso de Grandes Células B/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
Peripheral neuropathies should be recognized as the adverse effects of biological agents, especially anti-TNF agents. However, no solid clinical databases for biological agent-associated peripheral neuropathies (BAPN) have been established in Japan. Here we report two cases of peripheral neuropathy associated with anti-TNF agents. One was peroneal motor neuropathy. The other case was chronic inflammatory demyelinating polyradiculoneuropathy. In addition, we summarize the previous reports on BAPN and discuss their prevalence rate, pathogenesis and management.
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Antirreumáticos/efeitos adversos , Infliximab/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Antirreumáticos/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Japão , Masculino , Pessoa de Meia-IdadeRESUMO
Programmed cell death 1 (PD-1) is an immunosuppressive receptor that transduces an inhibitory signal into activated T cells. Although a single nucleotide polymorphism in the gene for PD-1 is associated with susceptibility to systemic lupus erythematosus, the role of PD-1 in systemic lupus erythematosus is still not well understood. In this study, we used NZB/W F1 mice, a model of lupus-like nephritis, to examine the function of PD-1 and its ligands. PD-1 was predominantly expressed on CD4(+) T cells that infiltrated the kidney, and CD4(+)PD-1(high) T cells produced higher levels of IFN-gamma than CD4(+)PD-1(low) or CD4(+)PD-1(-) T cells. Stimulation with PMA/ionomycin caused splenic CD4(+)PD-1(+) T cells to secrete high levels of IFN-gamma, IL-10, low levels of TNF-alpha, faint levels of IL-2, IL-21, and no IL-4, IL-17. In vivo anti-PD-1 mAb treatment reduced the number of CD4(+)PD-1(+) T cells in the kidney of NZB/W F1 mice and significantly reduced their mortality rate (p = 0.03). Conversely, blocking PD-L1 using an anti-PD-L1 mAb increased the number of CD4(+)PD-1(+) T cells in the kidney, enhanced serum IFN-gamma, IL-10, and IgG2a ds-DNA-Ab levels, accelerated the nephritis, and increased the mortality rate. We conclude that CD4(+)PD-1(high) T cells are dysregulated IFN-gamma-producing, proinflammatory cells in NZB/W F1 mice.
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Anticorpos Monoclonais/farmacologia , Antígenos de Diferenciação/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Nefrite/metabolismo , Animais , Anticorpos Antinucleares/sangue , Anticorpos Monoclonais/imunologia , Antígenos de Diferenciação/imunologia , Antígeno B7-1/imunologia , Antígeno B7-1/metabolismo , Antígeno B7-H1 , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/patologia , Proliferação de Células , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Interferon gama/sangue , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/metabolismo , Camundongos , Nefrite/mortalidade , Nefrite/prevenção & controle , Peptídeos/imunologia , Peptídeos/metabolismo , Proteína 2 Ligante de Morte Celular Programada 1 , Receptor de Morte Celular Programada 1 , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologia , Taxa de SobrevidaRESUMO
Sarcoidosis, a systemic inflammatory disease of unknown etiology, can affect any site in the body. A bone lesion was unexpectedly detected by fluorodeoxyglucose position emission tomography/computed tomography (FDG PET/CT) in a patient with multiorgan sarcoidosis. FDG PET/CT should be considered for the detection of clinically silent lesions of sarcoidosis.
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A 75-year-old woman with rheumatoid arthritis (RA) who was receiving methotrexate (MTX) therapy developed Epstein-Barr virus (EBV)-associated CD8(+) T-cell lymphoproliferative disorder (LPD) and meningoencephalitis. She was successfully treated with acyclovir and corticosteroids plus MTX cessation. T-cell LPD is relatively rare in RA patients receiving MTX. To our knowledge, this is the first report of CD8(+) T-cell LPD with EBV genome occurring during MTX therapy for RA. EBV infection should be carefully monitored to assess severe EBV-associated complications.
Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Transtornos Linfoproliferativos/imunologia , Metotrexato/efeitos adversos , Aciclovir/uso terapêutico , Idoso , Antivirais/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Linfócitos T CD8-Positivos/efeitos dos fármacos , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Feminino , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Hospedeiro Imunocomprometido , Imunofenotipagem , Linfonodos/imunologia , Linfonodos/patologia , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/virologia , Meningoencefalite/tratamento farmacológico , Meningoencefalite/imunologia , Meningoencefalite/virologia , Metilprednisolona/uso terapêuticoRESUMO
This study aimed to directly analyze the potential relationship of anti-nuclear antibodies (ANA) before and after the administration of TNF-α inhibitors (TNFi) with the appearance of anti-drug antibodies (ADrA) in patients with rheumatoid arthritis (RA). A total of 121 cases, viz., 38, 53, and 30 cases treated with infliximab (IFX), adalimumab (ADA), and etanercept (ETN), respectively, were enrolled. The ANA titers were measured using indirect immunefluorescence assay (IF-ANA) and multiplex flow immunoassay (ANA Screen) before and serially during the therapy. The anti-IFX antibodies (HACA) and anti-ADA antibodies (AAA) were measured with a radioimmunoassay. ADrA turned positive in 14 (36.8%) among 38 patients treated with IFX, and 16 (30.2%) among 53 treated with ADA. All of them were positive for IF-ANA before TNFi administration, while ADrA never appeared in any of the 15 patients negative for IF-ANA (< 40). IF-ANA of high titers (≥ 320 and ≥ 640) before IFX treatment showed a significant association with the appearance of HACA 52 weeks after IFX (P = 0.040 and 0.017, respectively), whereas AAA appearance was not related to IF-ANA titers before treatment. Moreover, IF-ANA of high titers before IFX treatment was significantly associated with inefficacy and discontinuation of the treatment. The positivity of anti-SS-A antibodies before therapy might be a risk factor for ADrA appearance in patients treated with IFX or ADA. The percentage of patients whose IF-ANA titers increased was significantly higher with IFX than with ADA or ETN treatments (P = 0.026 and 0.022, respectively). High ANA titers and positive ANA Screen after IFX therapy showed a significant association with HACA appearance and possibly led to treatment failure. Among the three TNFi, only IFX showed a close relationship with IF-ANA and ADrA appearance, suggesting the interaction of immunogenicity with autoimmunity as well as the advantage of ANA measurement before TNFi therapy.
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Adalimumab/imunologia , Anticorpos/imunologia , Antirreumáticos/imunologia , Artrite Reumatoide/tratamento farmacológico , Etanercepte/imunologia , Infliximab/imunologia , Adalimumab/uso terapêutico , Adulto , Idoso , Anticorpos Antinucleares/imunologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Etanercepte/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Cytomegalovirus (CMV) disease is a serious infectious complication in compromised hosts. Therefore, there are several studies on the diagnosis and prophylactic/pre-emptive therapy of CMV diseases in patients with solid organ transplants, bone marrow transplants, hematopoietic stem cell transplants, and HIV diseases. However, in patients with autoimmune disease, there are only few studies on the diagnosis and prediction of CMV diseases. In the present article, we described three autoimmune cases that developed CMV gastrointestinal disease because of therapy-related immunosuppression. Although all three patients had a low-level CMV antigenemia without diarrhea or melena, CMV was detected in the gastrointestinal tract tissue. We concluded that CMV-antigenemia assay has a limited value in the diagnosis and prediction of CMV gastrointestinal disease in patients with autoimmune diseases, and that immunohistochemical confirmation of CMV tissue involvement should be recommended especially when the typical clinical gastrointestinal manifestations are lacking.
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Infecções por Citomegalovirus/imunologia , Dermatomiosite/imunologia , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/imunologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Dermatomiosite/complicações , Dermatomiosite/tratamento farmacológico , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: To assess the diagnostic values of presepsin and procalcitonin in patients with rheumatoid arthritis (RA) by identifying those with bacterial infection METHOD: During June 2014-September 2015, 126 patients with RA and 25 healthy controls were enrolled. RA patients were divided into an infection group and a non-infection group. Infection was diagnosed by clinical symptoms, microbiological or radiographic methods, and good response to antibiotics. Concentrations of plasma presepsin, serum procalcitonin, C-reactive protein (CRP), and white blood cell counts (WBC) were measured and compared in each group. The correlations with the Sequential Organ Failure Assessment (SOFA) Score and these markers were calculated. RESULTS: RA patients included 26 patients in the infection group, 45 patients in the CRP-positive non-infection group (CRP > 0.3 mg/dL), and 55 patients in the CRP-negative non-infection group (CRP < 0.3 mg/dL). Levels of presepsin and procalcitonin in the infection group were highest and significantly higher than those in the CRP-positive non-infection group (presepsin 682.8 ± 158.1 pg/mL vs. 192.0 ± 12.0 pg/mL [P < 0.0001]; procalcitonin 4.052 ± 1.637 ng/mL vs. 0.120 ± 0.032 ng/mL [(P < 0.0001]). According to receiver operating characteristic curve (ROC) analysis, presepsin and procalcitonin levels appeared to have a higher diagnostic accuracy for infection than CRP or WBC. For the infection group, the SOFA Score positively correlated with the concentration of presepsin but not with that of procalcitonin. CONCLUSION: Presepsin and procalcitonin may be useful to identify infection in RA patients. Presepsin may better reflect infection severity than procalcitonin.
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Artrite Reumatoide/sangue , Infecções Bacterianas/sangue , Calcitonina/sangue , Receptores de Lipopolissacarídeos/sangue , Fragmentos de Peptídeos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/diagnóstico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Biomarcadores/sangue , Proteína C-Reativa , Estudos de Casos e Controles , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Adulto JovemRESUMO
Thioredoxin (TRX) is an oxidative stress-inducible biological antioxidant that is highly expressed in the synoviocytes of rheumatoid arthritis (RA) patients. There is much evidence that oxidative stress plays a key role in the inflammation and destruction of RA joints; the functional relationship between TRX and RA remains unknown, however. We therefore investigated the role played by TRX in the inflammatory and joint-damaging processes of RA using a murine model in which arthritis was induced by administering a mixture of anti-type II collagen monoclonal antibodies (mAb) and lipopolysaccharide (LPS). In Wt mice mAb/LPS injection induced neutrophil infiltration, cartilage destruction, and chondrocyte apoptosis within the joints, all of which were dramatically suppressed in TRX transgenic (TRX-Tg) mice. Moreover, the 8-hydoxy-2'-deoxyguanosine (8-OHdG) expression seen in Wt mice after mAb/LPS injection was almost completely inhibited in TRX-Tg mice. The administration of recombinant TRX also suppressed mAb/LPS-induced joint swelling in Wt mice. Taken together, these results suggest that TRX protects against arthritis and is a plausible candidate with which to develop novel therapies for the treatment of RA.
Assuntos
Artrite Reumatoide/prevenção & controle , Articulações/efeitos dos fármacos , Articulações/patologia , Tiorredoxinas/uso terapêutico , 8-Hidroxi-2'-Desoxiguanosina , Animais , Apoptose/efeitos dos fármacos , Artrite Reumatoide/patologia , Desoxiguanosina/análogos & derivados , Desoxiguanosina/biossíntese , Modelos Animais de Doenças , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Transgênicos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tiorredoxinas/genética , Fator de Necrose Tumoral alfa/metabolismoAssuntos
Síndromes de Imunodeficiência/diagnóstico , Interleucinas/sangue , Células Matadoras Ativadas por Linfocina/imunologia , Células Matadoras Naturais/imunologia , Neoplasias/diagnóstico , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Contagem de Linfócitos/métodos , Neoplasias/imunologia , Manejo de EspécimesAssuntos
Síndrome da Imunodeficiência Adquirida/diagnóstico , Linfócitos B/imunologia , Linfoma/diagnóstico , Linfócitos T/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Citometria de Fluxo , Humanos , Contagem de Linfócitos/métodos , Linfoma/imunologia , Neoplasias/diagnóstico , Neoplasias/imunologia , Valores de Referência , Manejo de EspécimesAssuntos
Doenças do Sistema Imunitário/imunologia , Interleucinas , Células Matadoras Ativadas por Linfocina , Células Matadoras Naturais , Neoplasias/imunologia , Linfócitos T Auxiliares-Indutores , Viroses/imunologia , Bioensaio , Ensaio de Imunoadsorção Enzimática , Humanos , Doenças do Sistema Imunitário/diagnóstico , Células Matadoras Ativadas por Linfocina/imunologia , Células Matadoras Naturais/imunologia , Neoplasias/diagnóstico , Viroses/diagnósticoRESUMO
We describe herein dermatomyositis (DM) associated with thyroid cancer in a 54-year-old woman. She was resistant to corticosteroids at first, but removal of the coexisting cancer resulted in improvement of DM. Reports on the association of DM with thyroid cancer are very few. However, recently, increasing incidence of thyroid cancer is pointed out. It is thought that increasing incidence reflects increased detection of subclinical disease due to increased diagnostic scrutiny, not an increase in the true occurrence of thyroid cancer. Thus, DM associated with thyroid cancer may be more frequent than we generally expected. We recommend that thyroid studies should be included in cancer investigations, particularly in DM cases resistant to corticosteroids.
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Adenocarcinoma Papilar/complicações , Dermatomiosite/complicações , Neoplasias da Glândula Tireoide/complicações , Adenocarcinoma Papilar/patologia , Adenocarcinoma Papilar/cirurgia , Dermatomiosite/tratamento farmacológico , Dermatomiosite/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Resultado do TratamentoRESUMO
Reversible posterior leukoencephalopathy syndrome (RPLS) has been identified in several connective tissue diseases. However, there are no reports of RPLS associated with Takayasu arteritis (TA). We report the first case of TA associated with RPLS. A 23-year-old woman presented with sudden headache and vomiting, followed by generalized tonic-clonic seizures and mental changes two weeks after administration of oral prednisolone. MRI showed hyperintense signals on T2 and FLAIR images in the bilateral temporal-parietal-occipital lobes, left frontal lobe, and left cerebellar hemisphere. Three weeks after starting control of convulsions and blood pressure with plasmapheresis, high-dose methylprednisolone, and cyclophosphamide, the clinical manifestations and abnormal signals on MRI completely resolved. These reversible clinical and radiological changes are consistent with vasogenic edema in the central nervous system, indicating RPLS. Although high-dose methylprednisolone and cyclophosphamide are thought to cause RPLS, we think that it is justified to use these agents, at least in difficult cases, for making a clear-cut differentiation from CNS vasculitis, as long as blood pressure and fluid volume are well controlled. Moreover, we suggest that RPLS should be included in differential diagnosis of acute neurological changes in connective tissue diseases, including TA.
Assuntos
Encéfalo/patologia , Síndrome da Leucoencefalopatia Posterior/patologia , Arterite de Takayasu/patologia , Adulto , Ciclofosfamida/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Imageamento por Ressonância Magnética , Metilprednisolona/uso terapêutico , Plasmaferese , Síndrome da Leucoencefalopatia Posterior/complicações , Síndrome da Leucoencefalopatia Posterior/terapia , Arterite de Takayasu/complicações , Arterite de Takayasu/terapia , Resultado do TratamentoRESUMO
OBJECTIVE: To examine whether serum procalcitonin (PCT) concentrations are useful for distinguishing bacterial infections from disease flares in patients with systemic autoimmune diseases. METHODS: Patients with systemic autoimmune diseases who were admitted to our hospitals due to either a suspected deterioration of their primary diseases or an infectious disease were enrolled. Serum PCT levels were measured in 99 serum samples of 98 patients who had elevated serum C-reactive protein (CRP) levels; 29 samples were obtained from patients with bacterial infections, and 70 samples were obtained from patients with disease deterioration without a detectable infection. The diagnostic accuracy, sensitivity, and specificity for identifying a bacterial infection were estimated using the receiver-operating characteristic curve. Multiple logistic regression analysis was also done with PCT level, age, sex, steroid dose, and use of immunosuppressive agents. RESULTS: Serum PCT levels were higher in the bacterial infection group than in the disease flare group (mean +/- SD, 4.539 +/- 9.677 vs 0.116 +/- 0.127; p < 0.0001). The diagnostic accuracy of PCT for bacterial infection was 0.797, sensitivity 53.3%, and specificity 97.1%. On multivariate analysis, the odds ratio of a PCT > or = 0.5 ng/ml was significant (OR 59.085, 95% CI 7.705 453.088, p < 0.0001) for identifying bacterial infection. CONCLUSION: Elevated serum PCT levels have a good specificity for diagnosing bacterial infection in patients with systemic autoimmune diseases regardless of their dosage of oral corticosteroids and immunosuppressive agents.
Assuntos
Doenças Autoimunes/diagnóstico , Infecções Bacterianas/diagnóstico , Calcitonina/sangue , Precursores de Proteínas/sangue , Adulto , Idoso , Doenças Autoimunes/sangue , Doenças Autoimunes/complicações , Infecções Bacterianas/sangue , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To demonstrate the existence of oxidative stress and the role of the antioxidant thioredoxin (TRX) in Sjögren's syndrome (SS). METHODS: Labial biopsy specimens from patients with SS were analyzed immunohistochemically to detect 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE), nitrotyrosine, and TRX. Levels of TRX in saliva and plasma were quantified by ELISA. To analyze the effect of TRX on human salivary gland (HSG) cells, recombinant TRX (rTRX)-treated HSG cells were stimulated by interferon-gamma (IFN-gamma) for detecting interleukin 6 (IL-6) with ELISA and RT-PCR, or stimulated with IFN-gamma and anti-Fas antibody for analyzing Fas-induced apoptosis with PI/annexin V staining. RESULTS: Large amounts of 8-OHdG, 4-HNE, nitrotyrosine, and TRX were produced in salivary duct cells of SS patients, whether there was periductal lymphocytic infiltration or not. Strong TRX expression was detected in acinar cells from 13 of 19 SS specimens. Levels of salivary TRX were significantly higher in SS patients than in controls (p < 0.05), and were inversely related to the salivary flow rates in SS patients. Patients who showed acinar TRX expression had higher salivary TRX levels than those who did not (p < 0.05). Interferon-gamma-induced expression of IL-6 and Fas-mediated apoptosis in HSG cells were significantly suppressed by pretreating cells with rTRX. CONCLUSION: Parallel production of oxidative stress markers together with massive secretion of TRX suggests that oxidative stress induces TRX in the salivary gland. Moreover, suppression of IL-6 production and apoptosis by rTRX in HSG cells suggests TRX acts to protect the salivary glands of SS patients from tissue damage.
Assuntos
Antioxidantes/metabolismo , Estresse Oxidativo , Glândulas Salivares , Síndrome de Sjogren , Tiorredoxinas/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Aldeídos/metabolismo , Apoptose/fisiologia , Biomarcadores/metabolismo , Inibidores de Cisteína Proteinase/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Feminino , Humanos , Peróxido de Hidrogênio/metabolismo , Interferon gama/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Pessoa de Meia-Idade , Oxidantes/metabolismo , Saliva/química , Glândulas Salivares/citologia , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia , Síndrome de Sjogren/metabolismo , Síndrome de Sjogren/patologia , Tiorredoxinas/genética , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
Behçet's disease is rare in childhood. We describe a 10-year-old boy with neuro-Behçet's disease (NB) who presented with fever, headache, vertigo, and hearing loss. An examination of the cerebrospinal fluid (CSF) revealed pleocytosis as well as elevated protein and interleukin (IL)-6 levels. Brain magnetic resonance imaging (MRI) showed hyperintensity of the right thalamus and midbrain on T2-WI, and gadolinium (Gd) enhancement of left acoustic nerve origin. HLA-B51 was positive. Prednisolone combined with methotrexate resulted in a complete remission. Brain MRI and the CSF IL-6 level were useful for the diagnosis and monitoring of this pediatric patient with NB.