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1.
Int J Mol Sci ; 24(19)2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37834372

RESUMEN

The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. We summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. Other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA.


Asunto(s)
Osteoporosis , Espondiloartritis , Humanos , Proteínas Hedgehog , Espondiloartritis/tratamiento farmacológico , Huesos , Vía de Señalización Wnt
2.
Clin Exp Rheumatol ; 38(3): 436-441, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31858957

RESUMEN

OBJECTIVES: To investigate clinical and laboratory prognostic factors of remission after one year of follow-up in patients with polymyalgia rheumatica (PMR) treated with low-dose prednisone. METHODS: In this observational study, in a monocentric Italian Rheumatology Unit, we enrolled eighty-one consecutive PMR patients. Clinical and laboratory tests were performed every 3 months. Clinical remission was defined as the lack of symptoms, while laboratory remission was defined as erythrocyte sedimentation rate ≤40 mm/h and C-reactive protein (CRP) ≤0.5 mg/dl. RESULTS: Thirty-eight patients reached complete (clinical and laboratory) remission after 12 months of follow-up. A significant lower percentage of complete remission was seen in female gender compared to male (33.9 % vs. 78.2%, p=0.0001) at univariate analysis. No significant differences were found at baseline according to response to therapy during follow-up, while CRP values at the sixth month were significantly lower in patients who reached complete remission after one year (median: 0.4 mg/dl vs. 1 mg/dl, p=0.017). CRP<0.5 mg/dl at 6 months was independently associated with complete remission at 12 months in the multivariate analysis. CONCLUSIONS: The sixth month of therapy is a target for the management of PMR because it can help to identify patients at greater risk of exacerbations, who may benefit from a tighter follow-up and more aggressive therapeutic strategy. Higher CRP values at 6 months appear to be associated with a higher risk of longer steroid therapy.


Asunto(s)
Arteritis de Células Gigantes/diagnóstico , Polimialgia Reumática/diagnóstico , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Femenino , Arteritis de Células Gigantes/tratamiento farmacológico , Humanos , Masculino , Polimialgia Reumática/tratamiento farmacológico , Prednisona/uso terapéutico , Pronóstico , Inducción de Remisión
3.
Clin Exp Rheumatol ; 38(1): 88-93, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31140397

RESUMEN

OBJECTIVES: Axial spondyloarthritides (axSpA) are a group of disorders that share similar pathogenetic mechanisms and clinical picture. The aim of this retrospective multicentric study was to evaluate demographic and clinical differences between ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) patients. METHODS: Patients from 7 rheumatological centres in the Lazio region of Italy were included from January 1st, 2010 to April 1st, 2018, if they had undergone pelvic and/or spine radiographs or magnetic resonance imaging (MRI). Images were evaluated by one experienced radiologist in each centre who already had the clinical suspicion of axSpA. Clinical and therapeutic data were collected at the last observation visit. Categorical variables were presented with percentages and analysed by Chi squared test. Continuous variables were expressed as mean ± standard deviation and compared using the parametric unpaired t-test or the non-parametric Mann-Whitney U-test, when appropriate. p-values <0.05 were considered significant. RESULTS: 210 axSpA patients were included: 65.2% with AS and 34.7% with nr-axSpA. When comparing the two groups, AS patients had longer disease duration, were older, were more frequently males, had a greater diagnostic delay and a higher body mass index than the nr-axSpA patients (p<0.0001, p<0.0001, p=0.003 p=0.007, and p=0.04, respectively). The peripheral joints of the nr-axSpA patients were more frequently involved, had higher frequency of inflammatory bowel disease, higher C-reactive protein levels and lower frequency of HLA-B27 positivity (p=0.005, p=0.007, p=0.01, and p=0.01, respectively). TNF inhibitors were used in 87.8% patients with AS and 78.3% with nr-axSpA (p=0.04). More fat metaplasia was observed on MRI in the nr-axSpA group than in the AS group at sacroiliac joints (p=0.003), and more backfills were detected in the AS group on spine-MRI (p=0.003). Spine-bone marrow oedema was more prevalent in AS than in nr-axSpA (p=0.04), and more sclerosis and backfill were found in AS (p=0.003 and p=0.01, respectively). CONCLUSIONS: In clinical practice, distinctive features in AS and nr-axSpA patients emerged. Imaging is crucial in guiding the choice of treatment in order to control disease activity and inflammation.


Asunto(s)
Espondiloartritis/fisiopatología , Espondilitis Anquilosante/fisiopatología , Diagnóstico Tardío , Demografía , Femenino , Humanos , Italia , Masculino , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Espondiloartritis/diagnóstico , Espondilitis Anquilosante/diagnóstico
4.
Ann Rheum Dis ; 76(7): 1228-1236, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28119289

RESUMEN

OBJECTIVE: To define the synovial characteristics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical and ultrasound remission achieved by combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockers. METHODS: Patients with RA in remission (n=25) (disease activity score (DAS)<1.6 for at least 6 months), patients with RA in low disease activity (LDA) (n=10) (1.6

Asunto(s)
Adalimumab/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Etanercept/uso terapéutico , Adulto , Anciano , Antígenos CD/metabolismo , Antígenos CD20/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Artritis Psoriásica/diagnóstico por imagen , Artritis Psoriásica/metabolismo , Artritis Psoriásica/patología , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Complejo CD3/metabolismo , Colágeno/metabolismo , Quimioterapia Combinada , Femenino , Humanos , Inmunohistoquímica , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Receptores de Complemento 3d/metabolismo , Recurrencia , Inducción de Remisión , Membrana Sinovial/diagnóstico por imagen , Membrana Sinovial/metabolismo , Membrana Sinovial/patología , Sinovitis/diagnóstico por imagen , Sinovitis/metabolismo , Sinovitis/patología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Ultrasonografía , Ultrasonografía Doppler
8.
Rheumatology (Oxford) ; 53(5): 875-81, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24407233

RESUMEN

OBJECTIVE: The objective of this study was to determine whether BMI and gender could lead to a different response rate to anti-TNF agents in patients affected by axial SpA. METHODS: One hundred and seventy patients with active axial SpA (defined as a BASDAI ≥ 4) treated with an anti-TNF agent [adalimumab (ADA), etanercept (ETA), infliximab (IFX)] were retrospectively evaluated. Patients were divided according to the baseline BMI as normal weight (BMI < 25), overweight (BMI 25-30) and obese (BMI ≥ 30). After 12 months of treatment a 50% improvement of the initial BASDAI (BASDAI50) was the primary end point and BASDAI ≤ 1 was the secondary end point. RESULTS: After 12 months of anti-TNF treatment, 67.8% of men and 46.2% of women reached the BASDAI50 (P = 0.01). According to BMI categories, the rate of BASDAI50 achievement decreased from 72.8% in normal weight subjects to 54.5% in overweight and 30.4% in obese subjects (P < 0.001). In the logistic regression analysis, the best independent predictors of failure to obtain a BASDAI50 response at the 12th month of therapy in axial SpA patients were female gender [odds ratio (OR) 3.23 (95% CI 1.52, 7.14)] and a BMI ≥ 30 [OR 3.57 (95% CI 1.15, 11.11)]. Analysing outcomes based on IFX therapy (the larger subgroup), the BASDAI50 response rate fell from 79.0% in normal weight subjects to 56.7% in overweight and 16.7% in obese subjects (P < 0.001). No significant differences were observed with ADA and ETA. CONCLUSION: Data suggest that being female, overweight and mostly obese is associated with a lower rate of success in obtaining response status in axial SpA patients treated with anti-TNF drugs. Body weight could represent a modifiable factor to reach the best outcome in axial SpA patients treated with TNF blockers.


Asunto(s)
Antirreumáticos/uso terapéutico , Vértebra Cervical Axis , Peso Corporal/fisiología , Factores Sexuales , Espondiloartritis/tratamiento farmacológico , Espondiloartritis/fisiopatología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Adulto , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Índice de Masa Corporal , Etanercept , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina G/uso terapéutico , Infliximab , Modelos Logísticos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Sobrepeso/complicaciones , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento
9.
Ann Rheum Dis ; 71(9): 1461-5, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22402140

RESUMEN

OBJECTIVES: Vascular endothelial growth factor (VEGF) is thought to play an important role in systemic sclerosis (SSc) pathogenesis. It was found to be upregulated in the serum and in the affected skin of scleroderma patients. However, its involvement in scleroderma lung disease is not clear. This study aimed to evaluate VEGF concentration in the bronchoalveolar lavage fluid (BALF) of scleroderma patients with interstitial lung disease, to correlate the cytokine levels in plasma and in the lung with pulmonary functional, radiological and cellular parameters, and with the progression of lung disease. METHODS: BALF and plasma VEGF concentrations were analysed by ELISA in 55 SSc patients with lung disease and 17 controls. Cytokine real-time PCR messenger RNA expression in alveolar macrophages was assessed. Lung involvement progression was evaluated after a 1-year follow-up. RESULTS: VEGF was found to be significantly lower in the BALF of scleroderma patients compared with controls. The lowest concentrations were observed in SSc patients with alveolitis. A decreased VEGF expression in alveolar macrophages was found in SSc patients with alveolitis. VEGF concentration in BALF correlated inversely with the ground glass score on high-resolution CT and with BALF neutrophil cell count. Moreover, SSc patients with a lower VEGF concentration showed a worsening in the interstitial score at follow-up. CONCLUSIONS: Scleroderma interstitial lung disease is characterised by a VEGF deficiency. Lower concentrations were found in patients with progression of lung disease.


Asunto(s)
Enfermedades Pulmonares Intersticiales/metabolismo , Esclerodermia Sistémica/metabolismo , Factor A de Crecimiento Endotelial Vascular/deficiencia , Líquido del Lavado Bronquioalveolar/química , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/etiología , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor A de Crecimiento Endotelial Vascular/análisis
10.
Expert Rev Proteomics ; 9(1): 33-46, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22292822

RESUMEN

The development of new separation techniques and different mass spectrometry instrumental devices, as well as the great availability of specific reactants, offers ample choice to scientists for carrying out high-throughput proteomic studies and being competitive in the field today. However, the different options available often do not provide comparable results, which can be linked to factors such as the strategy adopted, the nature of the sample and the instrumental availability. In this critical review, the results obtained so far in the study of human saliva by different proteomic approaches will be compared and discussed.


Asunto(s)
Proteoma , Saliva/química , Cromatografía Líquida de Alta Presión , Electroforesis en Gel Bidimensional , Humanos , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
11.
Clin Immunol ; 138(1): 107-16, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21056009

RESUMEN

We analyzed peripheral blood (PB) and synovial fluid (SF) mononuclear cells from 16 rheumatoid arthritis (RA), 9 spondyloarthritis (SpA), 3 microcrystal arthritis patients, to define the presence of Th17 and Th1 and their relationship with inflammatory activity, and TCR-zeta chain and ZAP-70 levels. Th17 were significantly higher in SF than in PB and more abundant in microcrystal arthritis patients compared to the other groups. Irrespectively of the diagnosis, SF Th17 percentages correlated with joint (SF total leukocyte count, neutrophil percentage) and systemic (C reactive protein [CRP], fibrinogen, erythrocyte sedimentation rate) inflammation markers. SF Th1 percentages directly correlated with inflammation and disease activity (CRP, swollen joint count [SJC]) indices in SpA, but not in RA patients. These observations support the role of Th17 in the pathogenesis of inflammatory arthritides. The TCR-zeta(dim) lymphocytes in SF were found to produce the highest amounts of cytokines including IL-17, whereas no ZAP-70 impairment was associated to Th17.


Asunto(s)
Artritis/inmunología , Artritis/patología , Líquido Sinovial/citología , Células Th17/inmunología , Células Th17/patología , Adulto , Anciano , Anciano de 80 o más Años , Artritis/diagnóstico , Artritis/metabolismo , Células Sanguíneas/inmunología , Células Sanguíneas/patología , Sedimentación Sanguínea , Proteína C-Reactiva/metabolismo , Recuento de Células , Femenino , Fibrinógeno/metabolismo , Humanos , Inflamación/patología , Interferón gamma/metabolismo , Leucocitos/patología , Activación de Linfocitos/inmunología , Linfocitos/patología , Masculino , Persona de Mediana Edad , Monocitos/patología , Neutrófilos/patología , Receptores de Antígenos de Linfocitos T/metabolismo , Líquido Sinovial/inmunología , Líquido Sinovial/metabolismo , Células TH1/inmunología , Células TH1/metabolismo , Células TH1/patología , Células Th17/metabolismo , Proteína Tirosina Quinasa ZAP-70/metabolismo
12.
Mol Med ; 17(9-10): 901-9, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21607290

RESUMEN

The aim of the present study was to determine whether different subsets of B cells characterize synovial fluid (SF) or synovial tissue (ST) of seropositive or seronegative rheumatoid arthritis (RA) with respect to the peripheral blood (PB). PB, SF and ST of 14 autoantibody (AB)-positive (rheumatoid factor [RF]-IgM, RF-IgA, anti-citrullinated peptide [CCP]), 13 negative RA and 13 no-RA chronic arthritides were examined for B-cell subsets (Bm1-Bm5 and IgD-CD27 classifications), zeta-associated protein kinase-70 (ZAP70) expression on B cells and cytokine levels (interleukin [IL]-1ß, tumor necrosis factor [TNF]-α, IL-6, IL-8 and monocyte chemotactic protein [MCP]-1). Synovial tissues were classified as aggregate and diffuse patterns. No differences were found in B-cell percentages or in subsets in PB and SF between AB(+) and AB(-) RA and no-RA. In both AB(+) and AB(-) RA (and no-RA), the percentage of CD19(+)/ZAP70(+) was higher in SF than in PB (AB(+): P = 0.03; AB(-): P = 0.01; no-RA: P = 0.01). Moreover, SF of both AB(+) and AB(-) RA (and no-RA) patients was characterized by a higher percentage of IgD-CD27(+) and IgD-CD27(-) B cells and lower percentage of IgD(+)CD27(-) (P < 0.05) B cells compared to PB. In SF, ZAP70 positivity is more represented in B cell CD27(+)/IgD(-)/CD38(-). The aggregate synovitis pattern was characterized by higher percentages of Bm5 cells in SF compared with the diffuse pattern (P = 0.05). These data suggest that no difference exists between AB(+) and AB(-) in B-cell subset compartmentalization. CD27(+)/IgD(-)/ZAP70(+) memory B cells accumulate preferentially in the joints of RA, suggesting a dynamic maturation of the B cells in this compartment.


Asunto(s)
Artritis Reumatoide/inmunología , Autoanticuerpos/inmunología , Subgrupos de Linfocitos B/inmunología , Articulaciones/inmunología , Proteína Tirosina Quinasa ZAP-70/inmunología , Adulto , Anciano , Artritis Reumatoide/genética , Artritis Reumatoide/metabolismo , Autoanticuerpos/sangre , Autoanticuerpos/metabolismo , Subgrupos de Linfocitos B/metabolismo , Subgrupos de Linfocitos B/patología , Biomarcadores/metabolismo , Citocinas/inmunología , Citocinas/metabolismo , Femenino , Citometría de Flujo , Humanos , Inmunoglobulina D/inmunología , Inmunoglobulina D/metabolismo , Inmunohistoquímica , Memoria Inmunológica/inmunología , Interleucinas/inmunología , Interleucinas/metabolismo , Articulaciones/metabolismo , Articulaciones/patología , Masculino , Persona de Mediana Edad , Factor Reumatoide/inmunología , Factor Reumatoide/metabolismo , Líquido Sinovial/inmunología , Líquido Sinovial/metabolismo , Membrana Sinovial/inmunología , Membrana Sinovial/metabolismo , Membrana Sinovial/patología , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/inmunología , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismo , Adulto Joven , Proteína Tirosina Quinasa ZAP-70/genética , Proteína Tirosina Quinasa ZAP-70/metabolismo
13.
Ann Rheum Dis ; 70(1): 172-5, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21097799

RESUMEN

OBJECTIVES: Treatment of rheumatoid arthritis (RA) should aim at full remission. The aims of this study were to define: (1) how many patients reached ultrasound power Doppler (US-PD) remission in a cohort of patients with early RA (ERA) compared with longstanding RA (LSRA); (2) possible predictors of US-PD remission; and (3) how many patients with and without US-PD remission relapsed after 1 year of follow-up in ERA and LSRA. METHODS: 48 patients with ERA and 46 with LSRA with disease activity score <1.6 underwent US assessment. Six hand and wrist joints were studied for active synovitis. 56.2% of patients with ERA and 50.0% of those with LSRA fulfilled American College of Rheumatology (ACR) remission criteria. RESULTS: 43.7% of patients with ERA and 17.4% of those with LSRA had no evidence of synovitis at US evaluation. Using a stricter clinical definition of remission (ie, ACR criteria), US evaluation confirmed clinical remission in 66.7% of patients with ERA and 26.1% of those with LSRA. Early disease was predictive of clinical US remission. 20.0% of patients with RA who had a negative PD signal at the US evaluation had a flare during the 12-month follow-up period compared with 47.1% of patients who had a positive PD signal. CONCLUSION: US-PD remission occurs in half of patients with ERA and in a minority of patients with LSRA in clinical remission. Early disease seems to be the major determinant of full remission.


Asunto(s)
Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Adulto , Anciano , Antirreumáticos/uso terapéutico , Métodos Epidemiológicos , Femenino , Articulaciones de la Mano/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Inducción de Remisión , Sinovitis/diagnóstico por imagen , Resultado del Tratamiento , Ultrasonografía Doppler en Color , Articulación de la Muñeca/diagnóstico por imagen
14.
Ann Rheum Dis ; 70(7): 1292-5, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21515600

RESUMEN

OBJECTIVES: To identify predictors of clinical remission as well as of no x-ray progression in a cohort of early rheumatoid arthritis (ERA) treated with a tight-control protocol. METHODS: A total of 121 consecutive patients with ERA were treated to reach European League Against Rheumatism (EULAR) and/or American College of Rheumatology (ACR) clinical remission with methotrexate (MTX) for 3 months, then with a combination with anti-tumour necrosis factor if the patient did not achieve a 44-joint Disease Activity Score (DAS44) ≤2.4. At baseline and after 12 months all the patients had hand and foot joint radiographs. Very early rheumatoid arthritis (VERA) was defined as a disease with symptoms of less than 12 weeks. RESULTS: In all, 46.3% of the patients reached DAS remission and 24.8% achieved ACR remission. More than 60% of patients reached remission with MTX. Male sex and an erythrocyte sedimentation rate <35 mm/h at onset arose as significant predictors of EULAR remission, while VERA disease was the only predictor of ACR remission. At baseline, 28.1% of the patients were erosive. Multivariate analysis demonstrated that the only independent predictor of erosiveness was 'not having VERA disease'. After 12 months, VERA was the only factor predicting a lack of new erosions. CONCLUSIONS: VERA represents the best therapeutic opportunity in clinical practice to achieve a complete remission and to stop the erosive course of rheumatoid arthritis.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Adulto , Anciano , Artritis Reumatoide/diagnóstico por imagen , Sedimentación Sanguínea , Progresión de la Enfermedad , Quimioterapia Combinada , Diagnóstico Precoz , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Pronóstico , Radiografía , Inducción de Remisión , Factores Sexuales , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores
15.
Respir Res ; 12: 22, 2011 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-21314931

RESUMEN

BACKGROUND: ß-thymosins play roles in cytoskeleton rearrangement, angiogenesis, fibrosis and reparative process, thus suggesting a possible involvement in the pathogenesis of systemic sclerosis. The aim of the study was to investigate the presence of thymosins ß4, ß4 sulfoxide, and ß10 in bronchoalveolar lavage fluid of scleroderma patients with interstitial lung disease and the relation of these factors with pulmonary functional and radiological parameters. METHODS: ß-thymosins concentrations were determined by reverse phase-high performance liquid chromatography-electrospray-mass spectrometry in the bronchoalveolar lavage fluid of 46 scleroderma patients with lung involvement and of 15 controls. RESULTS: Thymosin ß4, ß4 sulfoxide, and ß10 were detectable in bronchoalveolar lavage fluid of patients and controls. Thymosin ß4 levels were significantly higher in scleroderma patients than in controls. In addition, analyzing the progression of scleroderma lung disease at one-year follow-up, we have found that higher thymosin ß4 levels seem to have a protective role against lung tissue damage. Thymosin ß4 sulfoxide levels were higher in the smokers and in the scleroderma patients with alveolitis. CONCLUSIONS: We describe for the first time ß-thymosins in bronchoalveolar lavage fluid and their possible involvement in the pathogenesis of scleroderma lung disease. Thymosin ß4 seems to have a protective role against lung tissue damage, while its oxidation product mirrors an alveolar inflammatory status.


Asunto(s)
Enfermedades Pulmonares Intersticiales/metabolismo , Pulmón/metabolismo , Esclerodermia Sistémica/metabolismo , Timosina/metabolismo , Adulto , Anciano , Líquido del Lavado Bronquioalveolar/química , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión , Cromatografía de Fase Inversa , Femenino , Estudios de Seguimiento , Humanos , Pulmón/diagnóstico por imagen , Pulmón/inmunología , Pulmón/fisiopatología , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Capacidad de Difusión Pulmonar , Ciudad de Roma , Esclerodermia Sistémica/diagnóstico por imagen , Esclerodermia Sistémica/inmunología , Esclerodermia Sistémica/fisiopatología , Espectrometría de Masa por Ionización de Electrospray , Factores de Tiempo , Tomografía Computarizada por Rayos X , Capacidad Vital
16.
Front Med (Lausanne) ; 8: 669397, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34513861

RESUMEN

Background: Cardiovascular events (CVEs) are the first cause of death in patients with psoriatic arthritis (PsA). Depression is a recognized risk factor in cardiovascular events and is frequently associated with PsA. Flow-mediated dilatation (FMD) is a widely used method for assessing endothelial dysfunction, a parameter with strong prognostic implications for CVEs. The study aims to explore the relationship between FMD, depressive symptoms and serum cytokines in a cohort of patients with PsA. Patients and Methods: FMD was assessed in 50 consecutive PsA patients aged between 30 and 75 years without known cerebrovascular and coronary heart disease or diabetes. Depressive symptoms were reported using the related subscale of the Hospital Anxiety and Depression Scale (HDS). Disease features, activity indexes, and adjusted Framingham risk score (aFRS) were calculated. Serum level of IL-6, TNF-α, and IL-17A were also assessed. Results: In PsA patients (age 50.7 ± 10.2 years, male 42%, disease duration 5.9 ± 3.3 years, Disease Activity in PSoriatic Arthritis (DAPSA) score 14.0 ± 9.4) FMD inversely correlated with the severity of depressive symptoms according to HDS (ρ = -0.339, p = 0.016), age (ρ = -0.507, p = 0.001), aFRS (rs = -0.453, p < 0.001), duration of PsA (ρ = -0.507, p = 0.001), intensity of pain (ρ = -0.507, p = 0.001), and DAPSA (ρ = -0.507, p = 0.001). No statistically significant correlation was found between FMD or HDS and serum cytokines concentrations. HDS predicted FMD in a model adjusted for age, aFRS, PsA duration, and pain intensity (ß = -0.271, p = 0.008), with depressive symptoms contributing directly to 6.4% of the variance. Conclusions: Depressive symptoms correlate with endothelial dysfunction with an exposure-response pattern in our cohort of PsA patients.

17.
Clin Rheumatol ; 40(5): 1893-1902, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33009969

RESUMEN

OBJECTIVES: Depression is commonly associated with psoriatic arthritis (PsA), but its risk factors in these patients are largely unrecognized. Pro-inflammatory cytokines involved in the pathogenesis of PsA have been associated with depression in patients without autoimmune diseases. The aim of this study was to establish whether PsA patients with and without depressive symptoms differed for general or clinical variables and serum cytokines milieu. METHODS: One hundred and fifty consecutive patients with PsA were screened for depressive symptoms with Hospital Anxiety and Depression Scale (HADS-D). Patients with and without depressive symptoms were compared according to the prevalence of general risk factors for depression, comorbidities, PsA features and serum IL-6, TNF-α, and IL-17A. RESULTS: Fifty-eight patient (38.7%) had a depressive mood. Depressive symptoms were associated with female sex (p = 0.03) and current smoking (p = 0.05). Patients with and without depressive symptoms did not differ for general risk factors for depression and comorbidities. Depressed patients had more frequently psoriatic nail disease (p = 0.02) and significant physical disability (HAQ-DI ≥ 0.5) (p < 0.01) and were more frequently in moderate or high disease activity according to DAPSA score (p = 0.01). Depressed patients had higher serum IL-6 (p < 0.01) and comparable serum IL-17A and TNF-α. A cutoff of 2.27 pg/ml of serum IL-6 had the best ability to predict an HADS-D ≥ 8 (AUC 0.666 ± 0.044; p < 0.01). Multivariate logistic regression analysis confirmed that serum IL-6 ≥ 2.27 pg/ml was independently associated with depressive symptoms (OR 3.5; CI 1.6-7.8; p < 0.01). CONCLUSIONS: Higher serum Il-6 is associated with depressive symptoms. This association suggests a direct role of systemic inflammation in the modulation of mood in PsA patients. Key Points • High PsA disease activity and physical disability are associated with depression. • Higher serum levels of IL-6 are independently associated with depression in PsA. • IL-6 might play a direct role in the development of depression in PsA patients.


Asunto(s)
Artritis Psoriásica , Depresión , Artritis Psoriásica/complicaciones , Citocinas , Depresión/complicaciones , Depresión/epidemiología , Femenino , Humanos , Inflamación , Factor de Necrosis Tumoral alfa
18.
Arthritis Rheumatol ; 73(9): 1601-1613, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33750008

RESUMEN

OBJECTIVE: This study applied a synovitis score obtained during routine care from ultrasound (US)-guided biopsies of synovial tissue (ST) in patients with rheumatoid arthritis (RA) and patients with other inflammatory and noninflammatory joint diseases to identify pretreatment synovial biomarkers associated with disease characteristics, and to integrate the findings into a multiparameter nomogram for use in baseline prediction of diagnosis and treatment response in treatment-naive rheumatoid arthritis (RA) patients. METHODS: The study enrolled a total of 1,015 patients with various autoimmune diseases (545 patients with RA, 167 patients with psoriatic arthritis [PsA], 199 patients with undifferentiated peripheral inflammatory arthritis [UPIA], 18 patients with crystal-induced arthritis, 26 patients with connective tissue diseases, and 60 patients with osteoarthritis [OA] [as part of the SYNGem cohort]). All patients underwent a US-guided ST biopsy at baseline, and patients were then stratified according to disease phase. The KSS, along with disease characteristics and clinical outcomes, were incorporated into a nomogram for prediction of achievement of clinical remission in RA patients who were previously naive to treatment. In patients in whom a treat-to-target strategy was applied, remission was defined as change in the Disease Activity Score in 28 joints (DAS28) at 6 months after treatment initiation. RESULTS: The KSS significantly differed among RA patients, as well as PsA patients and UPIA patients, when compared to OA patients. In RA, the KSS directly correlated with the DAS28 and was related to autoantibody positivity in treatment-naive RA patients. Moreover, at baseline, treatment-naive RA patients achieving 6-month remission according to DAS28 had a lower KSS, shorter duration of symptoms (very early RA [VERA]), and lower disease activity than treatment-naive RA patients not achieving remission according to DAS28. Results of logistic regression analysis identified the following synergistic predictive factors of achievement of DAS28-based disease remission at 6 months: having a short disease duration (VERA), not having high disease activity, and having a KSS of <5 at baseline. A nomogram integrating these baseline clinical and histologic characteristics in treatment-naive RA patients yielded an up to 81.7% probability of achieving 6-month remission according to the DAS28. CONCLUSION: The KSS is a reliable tool for synovitis assessment on US-guided ST biopsy, contingent on the phase of the disease and the autoimmune profile of each patient. This tool could be integrated within a therapeutic response-predictive nomogram for the prediction of treatment response in RA patients who were previously naive to treatment.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Membrana Sinovial/diagnóstico por imagen , Sinovitis/diagnóstico por imagen , Anciano , Artritis Reumatoide/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nomogramas , Inducción de Remisión , Índice de Severidad de la Enfermedad , Ultrasonografía
19.
Clin Chem Lab Med ; 48(6): 829-34, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20298138

RESUMEN

BACKGROUND: The goal of our study was to evaluate the diagnostic performance of the anti-cyclic citrullinated peptide 2 (anti-CCP2) assay in patients with autoimmune and inflammatory disorders. METHODS: We tested the specificity and sensitivity of anti-CCP2 antibodies measured by ELISA in 787 patients with rheumatoid arthritis (RA), 1024 patients with other autoimmune/inflammatory rheumatic disease and 401 subjects without autoimmune rheumatic disease. The optimal cut-off value was defined as the value with the highest diagnostic accuracy (receiver operating characteristic curve analysis). Interval-specific likelihood ratios (LRs) were calculated for each range bounded by defined anti-CCP2 values. RESULTS: To distinguish between patients with RA and controls, the cut-off value with the highest diagnostic accuracy for anti-CCP2 was 2.8 U/mL. Comparing the optimal cut-off value for anti-CCP2 to that recommended by the manufacturer (5.0 U/mL), an increase in prevalence between the proportions of test-positive patients was found for RA, undifferentiated connective tissue disease and undifferentiated arthritis. Evaluating interval-specific LRs for the selected ranges bound by two anti-CCP2 values, in RA and diseased controls, the LRs were 0.40 for values <5.0 U/mL, 6.66 for 5.0-15.0 U/mL, 27.01 for 15.1-30.0 U/mL and 28.89 for >30.0 U/mL. CONCLUSIONS: The cut-off value of 2.8 U/mL for anti-CCP2 has the highest diagnostic accuracy. A value of anti-CCP2 >15 U/mL is associated with an increase in the likelihood of RA disease.


Asunto(s)
Artritis Reumatoide/diagnóstico , Autoanticuerpos/sangre , Péptidos Cíclicos/inmunología , Adulto , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Funciones de Verosimilitud , Masculino , Persona de Mediana Edad , Curva ROC , Enfermedades Reumáticas/diagnóstico
20.
Expert Opin Biol Ther ; 20(7): 813-821, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32401062

RESUMEN

BACKGROUND: Secukinumab (SEC) is effective for ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in randomized trials, but real-life data are lacking. RESEARCH DESIGN AND METHODS: Real-life, prospective observational study on 169 consecutive outpatients at baseline (T0) and at 6 (T6) and 12 months (T12) after starting SEC (39 AS, 23%; 130 PsA, 77%). RESULTS: Significant improvement was seen at T6 and T12 for all clinical variables, including TJC, SJC, ESR, CRP, DAPSA, ASDAS-CRP, and BASDAI, as well as in patient-reported outcomes like VAS-pain. By multivariable regression analysis, in AS patients high BASDAI at T0 correlated with diagnostic delay (R2 = 0.4; p = 0.009) and peripheral joint involvement (R2 = 0.4; p = 0.04). During follow-up, reduction of BASDAI positively correlated with high ESR (R2 = 0.65; p = 0.04). ASDAS-CRP at T0 positively correlated with high ESR (R2 = 0.34; p = 0.004). Reduction of ASDAS-CRP from T0 to T6 correlated with current smoking status (R2 = 0.42; p = 0.003). In PsA patients, reduction of DAPSA score from T0 to T12 is negatively correlated with the presence of metabolic syndrome (R2 = 0.41; p = 0.0025). SEC was well tolerated; 10 patients discontinued treatment for non-severe adverse events. CONCLUSIONS: Secukinumab is effective and safe in patients with AS and PsA in a real-life setting.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/patología , Índice de Masa Corporal , Diagnóstico Tardío , Fármacos Dermatológicos/efectos adversos , Femenino , Humanos , Hipersensibilidad/etiología , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/patología , Resultado del Tratamiento
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