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1.
J Clin Med ; 8(11)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752231

RESUMO

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group's cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The "ex-novo" occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies' positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.

2.
J Rheumatol ; 46(3): 279-284, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30442823

RESUMO

OBJECTIVE: To describe nailfold videocapillaroscopy (NVC) features of patients with antisynthetase syndrome (AS) and to investigate possible correlations with clinical and serological features of the disease. METHODS: We retrospectively analyzed NVC images of 190 patients with AS [females/males 3.63, mean age 49.7 ± 12.8 yrs, median disease duration 53.7 mos (interquartile range 82), 133 anti-Jo1 and 57 non-anti-Jo1-positive patients]. For each patient, we examined number of capillaries, giant capillaries, microhemorrhages, avascular areas, ramified capillaries, and the presence of systemic sclerosis (SSc)-like pattern. Finally, we correlated NVC features with clinical and serological findings of patients with AS. Concomitantly, a historical cohort of 75 patients with antinuclear antibody-negative primary Raynaud phenomenon (RP) and longterm followup was used as a control group (female/male ratio 4.13/1, mean age 53.9 ± 17.6 yrs) for NVC measures. RESULTS: NVC abnormalities were observed in 62.1% of AS patients compared with 29.3% of primary RP group (p < 0.001). An SSc-like pattern was detected in 67 patients (35.3%) and it was associated with anti-Jo1 antibodies (p = 0.002) and also with a longer disease duration (p = 0.004). Interestingly, there was no significant correlation between the presence of SSc-like pattern and RP, and only 47% of patients with SSc-like pattern had RP. CONCLUSION: NVC abnormalities are commonly observed in AS, independently from the occurrence of RP. The presence of an SSc-like pattern could allow identification of a more defined AS subtype, and prospective studies could confirm the association with clinical and serological features of AS.

3.
Clin Rheumatol ; 35(8): 1923-1929, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27320945

RESUMO

In rheumatoid arthritis (RA), treatment response is generally assessed using standard clinical disease activity measures. However, ultrasound has become increasingly popular among rheumatologists to monitor disease activity and response. The purpose of this analysis of ECOgraphic evaluation for STaging ARthritis (ECOSTAR) study data was to determine how ultrasound affects clinicians' decisions about changing treatment in RA. ECOSTAR was an observational, cohort study conducted between March 2010 and December 2012 at nine clinical centers in Italy in RA patients being considered for treatment change. After clinical evaluation of each patient, patients underwent diagnostic ultrasound (US) investigations and each patient was given a total echography score using a combination of scores for joint effusion, synovial hypertrophy, and power Doppler. The US results were provided to the clinicians and the influence of US on the clinicians' treatment choices were recorded. Ninety-five patients screened for study inclusion had confirmed RA (mean age 53.9 years; mean disease duration 8.9 years). Therapy changes were made by clinicians according to the hand and wrist joint US scores: score 0 appeared to have no influence on clinicians' decision to modify treatment, scores >0-3 were associated with a numerically higher estimated probability of not changing therapy than changing therapy, and scores >3 had a greater influence on the clinician to modify therapy and an increased probability of the clinician changing therapy versus not changing therapy. Ultrasonography scores appear to influence treatment decisions in patients with RA, with clinicians appearing less likely to alter treatment regimens in patients with low ultrasound scores and more likely to change treatment regimens when higher scores are obtained. Further research is warranted.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Tomada de Decisões , Ultrassonografia Doppler , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Comorbidade , Feminino , Mãos/diagnóstico por imagem , Humanos , Itália , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Esteroides/uso terapêutico , Articulação do Punho/diagnóstico por imagem , Adulto Jovem
4.
Arthritis Care Res (Hoboken) ; 68(6): 738-43, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26555747

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA) with concomitant hepatitis B virus (HBV) infection represents a therapeutic challenge due to the risk of HBV reactivation under immunosuppressive treatment. To date there are few data coming from anecdotal case reports that concern HBV reactivation following treatment with abatacept. This observational retrospective study was aimed to assess the safety profile of abatacept in this particular clinical setting. METHODS: Eleven Italian rheumatologic centers provided data from patients with RA and positive HBV serology treated with intravenous abatacept. HBV markers and clinical and laboratory data were checked at followup visits every 3 months. RESULTS: In total, 72 patients were included in the study: 47 inactive carriers, 21 occult carriers, and 4 chronic active carriers for HBV. At baseline all of the patients had normal liver function tests and low or undetectable HBV DNA levels, except for those with chronic active hepatitis. Thirteen patients received prophylaxis with lamivudine, and 4 received treatment with adefovir or tenofovir. At the end of the 24-month followup period, 49 patients were being treated. Data from 316 followup visits showed that abatacept was safe. No patients experienced reactivation of hepatitis B. Treatment withdrawals (23 patients) were due to lack of efficacy, subject decision/lost at followup, or adverse events not related to HBV infection. CONCLUSION: Our study provides reassuring data about the safety profile of abatacept in RA with concomitant HBV infection without universal antiviral prophylaxis. Further prospective studies are needed to confirm these preliminary results.


Assuntos
Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Hepatite B/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ativação Viral/efeitos dos fármacos
5.
Am J Otolaryngol ; 36(4): 590-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25841536

RESUMO

Cogan's syndrome is a rare systemic vasculitis of unknown origin. It is characterized by the presence of worsening audiovestibular and ocular symptoms that may manifest simultaneously or sequentially. No specific diagnostic laboratory tests or imaging studies exist. The diagnosis is clinical and should be established as early as possible so as to initiate prompt treatment with steroids and prevent rapid progression to deafness or blindness and potentially fatal systemic involvement. We report a case of association between Cogan's syndrome and ileal Crohn's disease which we believe deserves attention since, after an accurate review of the literature, we have found approximately 250 reports of patients with Cogan's syndrome, only 13 of whom with concurrent chronic inflammatory bowel disease; of these 13 cases, none experienced improvement after therapy. In the light of the good outcome obtained in our case, we proposed a valid treatment option with boluses of steroids, combined with early systemic immunosuppression and intra-tympanic steroid injections.


Assuntos
Apraxias/congênito , Síndrome de Cogan/complicações , Doença de Crohn/complicações , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Súbita/etiologia , Apraxias/complicações , Apraxias/diagnóstico , Apraxias/tratamento farmacológico , Audiometria , Síndrome de Cogan/diagnóstico , Síndrome de Cogan/tratamento farmacológico , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Diagnóstico Diferencial , Eletronistagmografia , Feminino , Glucocorticoides/administração & dosagem , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Súbita/diagnóstico , Perda Auditiva Súbita/tratamento farmacológico , Humanos , Imunossupressão/métodos , Injeções , Síndrome , Tomografia Computadorizada por Raios X , Membrana Timpânica , Adulto Jovem
6.
Semin Arthritis Rheum ; 44(5): 542-550, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25450240

RESUMO

OBJECTIVES: To systematically review the evidence for a synergistic effect of combining rehabilitation with biological anti-tumour necrosis factor (TNF) therapy in patients with ankylosing spondylitis (AS). METHODS: Data were analysed to identify the most effective rehabilitation programmes, the best endpoints for effectiveness, and patient subgroups most likely to benefit from combination therapy. Systematic MEDLINE and Embase searches were performed to identify studies evaluating rehabilitation programmes and biological therapy in patients with AS. Evidence was categorised by study type, and efficacy, adverse effects and other outcomes were summarised. RESULTS: Of the 75 studies identified, 13 investigated the combination of a rehabilitation programme with TNF inhibitor therapy, while the remainder studied rehabilitation with standard therapy (often not specified). Data from these few studies suggest that combined rehabilitation plus anti-TNF therapy is more effective in terms of symptom severity, disease activity, disability and quality-of-life indices versus biologic alone or rehabilitation with standard medical therapy, or, in non-comparative studies, compared with baseline. The most effective rehabilitation appears to be supervised or in-patient programmes with an educational component. Available data do not provide guidance on most appropriate endpoints or identify patients most likely to benefit from combination therapy. Combined, TNF inhibitor and rehabilitation therapy appear to have a synergistic effect, possibly due to increased adherence to exercise. Exercise regimes are more effective if supervised and include an education component. CONCLUSIONS: Further randomized, controlled trials comparing endpoints and investigating longer-term benefits of combining TNF inhibitors with rehabilitation in different AS subgroups are needed.


Assuntos
Terapia por Exercício , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Antirreumáticos/uso terapêutico , Terapia Combinada , Humanos , Espondilite Anquilosante/reabilitação , Resultado do Tratamento
7.
Am J Alzheimers Dis Other Demen ; 30(4): 390-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25204314

RESUMO

BACKGROUND: Subcortical vascular dementia relates to small-vessel disease and hypoperfusion, resulting in focal and diffuse ischemic white matter lesions. The main target of the disease are the frontal subcortical neural networks. There is no clinical standard definition of the pathology, on the contrary, everyday clinical practice suggests dominant behavioral alterations and dysexecutive syndrome. METHODS: The aim of this study was to investigate gait disorders, behavioral alteration, and drug intake of a subcortical population with dementia (n = 1155). A complete neuropsychological examination was conducted at baseline and every 6 months, and the results were compared. RESULTS: Our data suggest that there is a significant increment in apathy levels and a dramatic decrease in gait and equilibrium control in the patients examined during follow-up. CONCLUSION: Subcortical vascular dementia may be associated with gait and balance alteration and apathy per se; we suggest to implement clinical data with these major aspects.


Assuntos
Apatia/fisiologia , Demência Vascular/fisiopatologia , Transtornos Neurológicos da Marcha/fisiopatologia , Equilíbrio Postural/fisiologia , Substância Branca/patologia , Idoso , Idoso de 80 Anos ou mais , Demência Vascular/complicações , Progressão da Doença , Feminino , Seguimentos , Transtornos Neurológicos da Marcha/etiologia , Humanos , Masculino
8.
Rheumatology (Oxford) ; 54(5): 891-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25339643

RESUMO

OBJECTIVE: The aim of this study was to develop and validate an algorithm to assist the attribution of neuropsychiatric (NP) events to underlying disease in SLE patients. METHODS: Phase 1 identified and categorized candidate items to be included in the algorithm for the attribution of an NP event to SLE and their relative weights through a literature-informed consensus-driven process. Using a retrospective training cohort of SLE, phase 2 validated items selected in phase 1 and refined weights through a data-driven process, fitting items as independent variables and expert evaluation (clinical judgement) as reference standard in logistic models. Phase 3 consisted of a validation process using an external multicentre retrospective SLE cohort. RESULTS: Phase 1 identified four different items: timing of the NP event, type of event, confounding factors and favouring factors. The training and validating cohorts included 228 and 221 patients, respectively. Each patient experienced at least one NP event characterized using the ACR case definition. In these samples, items selected in phase 1 showed good performance in discriminating patients with NPSLE: the area under the receiver operating characteristic curve using dichotomous outcomes was 0.87 in the training set and 0.82 in the validating set. Relevant cut-offs of the validated score identify events with a positive predictive value of 100% (95% CI 93.2, 100) and 86.3% (95% CI 76.2, 93.2) in the training and validating cohorts, respectively. CONCLUSION: A new algorithm based on a probability score was developed and validated to determine the relationship between NP events and SLE.


Assuntos
Algoritmos , Transtornos Cognitivos/etiologia , Cefaleia/etiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Modelos Estatísticos , Transtornos do Humor/etiologia , Adulto , Transtornos Cognitivos/epidemiologia , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Cefaleia/epidemiologia , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/epidemiologia , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/epidemiologia , Prevalência , Curva ROC , Padrões de Referência , Estudos Retrospectivos
9.
Ann Rheum Dis ; 73(4): 716-21, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23505228

RESUMO

OBJECTIVE: The polymorphism 158V/F of Fc fragment of IgG (FCGR) type 3A may influence the response to rituximab (RTX) in rheumatoid arthritis (RA). We investigated the FCG3A polymorphism in a large cohort of RA patients treated with RTX, also by considering the possible loss of response from month +4 to +6 after RTX and the presence of established predictors of response. METHODS: The study analysed 212 RA patients. European League Against Rheumatism (EULAR) response was evaluated at months +4 and +6 after the first RTX infusion. The FCGR3A polymorphism was analysed by PCR followed by Sanger sequencing. RESULTS: The FCGR3A genotypes were associated with EULAR response (good or moderate) at month +6 (response in 34/38 (89.5%) VV vs 70/106 (66%) VF and in 51/77 (66.2%) FF patients; p=0.01), but not at month +4 (response in 32/37 (86.5%) VV vs 69/102 (67.6%) VF and 53/73 (72.6%) FF patients; p=0.09). Loss of response was observed only in VF and FF carriers ((VV vs VF vs FF: 0/37 (0%) vs 11/102 (10.8%) vs 12/73 (16.4%); p=0.02)). Probability of response at month +6 was very high when at least two of the three following items selected by multivariate analysis were present: positive rheumatoid factor and/or anticyclic citrullinated peptide antibodies, previous treatment with ≤ 1 anti-tumor necrosis factor (TNF) agent, and 158VV FCGR3A genotype (p<0.0001; OR 7.9, 95% CI 4.1 to 15.1). CONCLUSIONS: The 158VV FCGR3A genotype was associated with response to RTX in a large cohort of RA patients. Patient genotyping may be helpful to plan RTX treatment, and may be integrated with clinical predictors.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Receptores de IgG/genética , Idoso , Biomarcadores/sangue , Resistência a Medicamentos/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Prognóstico , Estudos Retrospectivos , Rituximab , Análise de Sequência de DNA/métodos , Resultado do Tratamento
10.
Rheumatology (Oxford) ; 51(1): 157-68, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22075066

RESUMO

OBJECTIVE: To analyse risk factors and comorbidities potentially associated with CNS involvement in a large cohort of Italian patients affected by SLE. METHODS: A number of generic (not strictly SLE related) and specific (disease related) risk factors to which all patients have been exposed in the span of 5 years before the first neuropsychiatric (NP) event or before the last available observation were checked for and their distribution was analysed in 959 SLE patients with and without NP involvement; all the first NP events that occurred in a time frame of 10 years were recorded and categorized as SLE related or SLE unrelated. RESULTS: Three hundred and twenty-six SLE patients with and 633 SLE patients without NP manifestations were included in the study. A total of 469 NP events were recorded. Headache (26.1%), cerebrovascular events (22.7%), mood disorders (8.9%), seizures (14.4%) and cognitive dysfunctions (9.5%) were the most frequent SLE-related NP events. More risk factors [mean 4.52 (2.44) vs 3.73 (2.01); P < 0.0001] were observed in patients with than without NP involvement. Overall, aPLs, LA and APS were factors more strongly associated with NP involvement. CONCLUSIONS: In SLE, NP involvement and aPLs were confirmed as closely related. Furthermore, other modifiable generic risk factors, such as hypertension, carotid vasculopathy and dyslipidaemia, appeared to be related to the occurrence of cerebral vascular accident (CVA) and cognitive dysfunctions, suggesting the need for a more intensive preventive strategy to optimize the management of NP lupus.


Assuntos
Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Transtornos Mentais/etiologia , Adulto , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/epidemiologia , Síndrome Antifosfolipídica/psicologia , Biomarcadores/sangue , Comorbidade , Métodos Epidemiológicos , Feminino , Transtornos da Cefaleia/epidemiologia , Transtornos da Cefaleia/etiologia , Humanos , Itália/epidemiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/epidemiologia , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
11.
J Rheumatol ; 34(3): 588-91, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17343303

RESUMO

Methylprednisolone and cyclophosphamide pulse therapies are the most commonly used for transverse myelopathy in neuropsychiatric lupus. Little is known about the efficacy of other immunosuppressors. We describe the case of a 33-year-old woman with systemic lupus erythematosus, who developed a tranverse myelopathy, beginning with a hiccup due to involvement of the medulla oblongata; despite pulses of methylprednisolone plus azathioprine and cyclosporine therapy, she developed paraparesis with involvement of the cervical spine cord. After oral cyclophosphamide, the lesion remained active. Subsequent therapy with mycophenolate mofetil and continuous intravenous infusions of dexamethasone resulted in reduction of the lesion's size, disappearance of magnetic resonance imaging enhancement, and a complete recovery.


Assuntos
Anti-Inflamatórios/administração & dosagem , Dexametasona/administração & dosagem , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ácido Micofenólico/análogos & derivados , Mielite/tratamento farmacológico , Adulto , Imagem Ecoplanar , Feminino , Humanos , Infusões Intravenosas , Lúpus Eritematoso Sistêmico/complicações , Ácido Micofenólico/uso terapêutico , Mielite/etiologia , Paraparesia/tratamento farmacológico , Paraparesia/etiologia
12.
Reumatismo ; 58(1): 50-8, 2006.
Artigo em Italiano | MEDLINE | ID: mdl-16639488

RESUMO

OBJECTIVES: To determine the role of antiphospholipid antibodies (aPL) and of Raynaud's phenomenon (RP) in the development of migraine in patients with systemic lupus erythematosus (SLE). METHODS: 50 unselected SLE patients and 20 rheumatoid arthritis (RA) controls underwent an interview to define the presence of migraine according to the guidelines of the International Headache Society (1988). Serological tests for aPL were performed in all patients. SLE patients were divided according to positivity for RP and/or aPL into 4 subsets: R-/aPL-, R-/aPL+, R+/aPL- and R+/aPL+. Data were analysed using Fisher's exact test, Chi-square test and U Mann-Whitney test. RESULTS: SLE and RA patients were similar for demographic and clinical features; aPL positivity was found in a greater proportion of SLE patients versus RA controls (68% vs 25%, p=0.0036). 31 of the 50 lupic patients (62%) and 7 of the 20 RA controls (35%) suffered from migraine (OR=3, CI:1-8.9). Among SLE and RA patients, migraine was associated with aPL positivity (p=0.027 and p=0.019). Analysing the combined effect of aPL and RP on migraine, in R+/aPL+ patients we detected an higher frequency of migraine (85.7%) with respect to the patients negative for these two features (27%, p=0.0051, OR=16, CI:2.2-118) and to the patients positive only for aPL (65%, p=0.0031, OR=6.2, CI:1.2-32). CONCLUSIONS: Migraine in SLE and RA associates with aPL positivity. The simultaneous presence of RP increases by 2,5 times the probability of having migraine, suggesting that cerebral vasospasm might be more common in patients with peripheral vasospasm, given the presence of aPL.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Lúpus Eritematoso Sistêmico/complicações , Transtornos de Enxaqueca/etiologia , Doença de Raynaud/etiologia , Vasoespasmo Intracraniano/etiologia , Adulto , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/imunologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/imunologia , Transtornos de Enxaqueca/fisiopatologia , Medição da Dor , Doença de Raynaud/imunologia , Fatores Socioeconômicos , Vasoespasmo Intracraniano/imunologia , Vasoespasmo Intracraniano/fisiopatologia
13.
J Rheumatol ; 32(6): 998-1005, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15940758

RESUMO

OBJECTIVE: To analyze tumor necrosis factor-alpha (TNF-alpha) synthesis by mononuclear cells stimulated with lipopolysaccharide (LPS) in patients with rheumatoid arthritis (RA). METHODS: TNF-alpha molecular expression and extracellular release were assessed in the peripheral blood mononuclear cells (PBMC) of 27 RA patients and 16 healthy blood donor controls during 8 hours of LPS stimulation. We also analyzed the mRNA expression of tristetraprolin (TTP), the major TNF-alpha mRNA destabilizing factor. TNF receptor p75 (TNFR 2) plasma concentrations were also tested in all patients. RESULTS: Controls and patients demonstrated a comparable wide range of TNF-alpha release capability, but patients achieved the peak value of protein release more quickly. Defining the median TNF-alpha release in controls as the cutoff value to distinguish high and low LPS-induced TNF-alpha-releasing phenotypes, patients with early RA (disease duration < 1 yr) belonged mainly to the low TNF-alpha producer subgroup, whereas patients with long-standing RA (> 1 yr) were prevalently high TNF-alpha producers. TTP molecular expression was higher in patients with shorter, than in patients with longer, disease duration. The profile of TNF-alpha release in patients with early RA changed significantly when retested after 6 months of therapy, while patients with long-standing disease maintained the same behavior as at baseline. Finally, a baseline low TNF-alpha-producer phenotype predisposed to a better responsiveness to disease modifying antirheumatic drugs. CONCLUSION: The LPS-induced TNF-alpha-releasing phenotype differs between cells obtained from RA patients with different disease durations and seems to influence the therapeutic outcome.


Assuntos
Artrite Reumatoide/imunologia , Proteínas de Ligação a DNA/biossíntese , Proteínas Imediatamente Precoces/biossíntese , Leucócitos Mononucleares/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/biossíntese , Dedos de Zinco , Antirreumáticos/uso terapêutico , Células Cultivadas , Proteínas de Ligação a DNA/genética , Feminino , Expressão Gênica , Humanos , Proteínas Imediatamente Precoces/genética , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/metabolismo , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Fatores de Tempo , Tristetraprolina , Fator de Necrose Tumoral alfa/genética , Dedos de Zinco/genética
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