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1.
Artigo em Inglês | MEDLINE | ID: mdl-32165035

RESUMO

OBJECTIVE: To analyze the safety and effectiveness of abatacept (ABA) given in routine care to patients with systemic sclerosis (SSc). METHODS: Retrospective multicenter observational study that enrolled patients with SSc treated with ABA. We collected epidemiological data and clinical outcomes. First, we analyzed the frequency of adverse effects. Secondly, we compared the evolution of different organ manifestations during ABA treatment. We collected data from 6 months before start of therapy to the last follow-up the following parameters: modified Rodnan Skin Score (mRSS), joints, lung and gastrointestinal involvement, concomitant medications, and laboratory tests. RESULTS: Data on twenty-seven patients with SSc were collected (93% females; 67% limited SSc). Rheumatoid arthritis was the most frequent concomitant autoimmune disease. ILD was present in 15 patients. Anti-Scl 70 antibodies were present in 13 patients and rheumatoid factor and ACPA antibodies were present in eight and seven patients respectively. The main indication to use abatacept was joint involvement (59%) followed by myositis (26%). A total of 16 adverse effects were reported in 28 months of abatacept treatment including five that required hospitalization. Most of them occurred in the first 3 months after starting abatacept. After 12 months, the number of tender and swollen joints decreased compared to baseline (p<0.03 and p<0.02 respectively). Moreover, a beneficial effect of abatacept on HAQ-DI at 3 and 6 months (p<0.05) and on morning stiffness at 6 and 12 months (p<0.03) was observed. We also observed a decrease in the modified Rodnan skin score (p<0.05). No changes in lung or gastrointestinal involvement were found. CONCLUSIONS: ABA demonstrated a good safety profile and seems to have some effectiveness on joint involvement and related disability in SSc patients treated in routine care.

2.
Respir Med ; 160: 105816, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31739247

RESUMO

Interstitial Lung Disease (ILD) is a common finding of Systemic Sclerosis (SSc) mainly presenting in the form of Nonspecific Interstitial Pneumonia (NSIP) and deeply affecting patients' prognosis. Beside NSIP, other types of ILD have been reported. The most recently described pattern is the so-called Combined-pulmonary emphysema and lung fibrosis, characterized by the coexistence of both upper lobes centrilobular and paraseptal emphysema and lower lobes ILD. We presented three cases of patients with SSc, in which High Resolution Computed Tomography examinations showed emphysema with atypical distribution and radiological presentation, without or with mild signs of fibrosing lung disease, that stabilized after immunosuppressive treatment.

3.
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.

4.
Joint Bone Spine ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31568838

RESUMO

Systemic sclerosis (SSc) is a connective tissue disease characterized by diffuse microangiopathy and immune dysregulation which ultimately result in widespread fibrosis of skin and internal organs. Although the 2013 EULAR/ACR criteria have allowed to improve the sensitivity for SSc diagnosis, it has recently come to light that the traditional subclassification into limited and diffuse cutaneous forms does not appear to fully capture the different phenotypes of the scleroderma spectrum. In this regard, a recent large cluster analysis-based study and other ongoing projects are trying to achieve a better stratification of SSc patients, as the disease course remains largely unpredictable to date. Recent preclinical studies and randomized controlled trials have yielded encouraging results with new drugs targeting inflammatory/immunological and fibrotic pathways. One of the main unmet needs in SSc remains the early identification of patients at high mortality risk, for whom aggressiveness of therapies ought to be determined and weighed against disease prognosis. Furthermore, lung and cardiac transplantation may also be taken into account in some carefully selected patients. Though the prognosis of SSc remains poor, an optimized stratification of patients along with the recent and ongoing advances in therapies could greatly impact the natural course of the disease in the near future. Moreover, it is envisioned that there will be an increasing need in the future to further develop combination therapies to better fight against this complex disease. In this review we discussed new insights into organ involvements and therapeutic options.

5.
Clin Exp Rheumatol ; 37 Suppl 119(4): 3-14, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587697

RESUMO

Systemic sclerosis (SSc) is a complex disorder characterised by the involvement of small arteries, microvessels and connective tissue, with deposition of fibrotic tissue and microvascular obliteration in the skin and internal organs. Due to the multifaceted nature of the disease, several articles are published in the medical literature every year, aimed at exploring different aspects of the pathogenesis, internal organ involvement and clinical aspects, and possible therapeutic approaches. In this article we have reviewed the literature on SSc of the past year, with the aim of identifying novel approaches that may help the treating physician in the clinical management of patients.


Assuntos
Microvasos/patologia , Escleroderma Sistêmico , Vasos Sanguíneos/patologia , Fibrose , Humanos , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/terapia , Pele
6.
J Control Release ; 310: 198-208, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31430501

RESUMO

Interstitial lung involvement in Systemic Sclerosis (SSc-ILD) is a complication with high morbidity and mortality. Specifically, engineered gold nanoparticles (GNPs) are proposed as targeted delivery system increasing efficacy of drugs with antifibrotic effect, such as tyrosine kinases. We aimed to test in vitro and in vivo the activity of targeted Imatinib (Im)-loaded GNP on SSc-ILD patients derived cells and in experimental model of lung fibrosis. GNPs functionalized with anti-CD44 and loaded with Im (GNP-HCIm) were synthesized. Lung fibroblasts (LFs) and alveolar macrophages from bronchoalveolar lavage fluids of SSc-ILD patients were cultured in presence of nanoparticles. GNP-HCIm significantly inhibited proliferation and viability inducing apoptosis of LFs and effectively reduced IL-8 release, viability and M2 polarization in alveolar macrophages. Anti-fibrotic effect of tracheal instilled GNP-HCIm was evaluated on bleomycin lung fibrosis mouse model comparing effect with common route of Im administration. GNP-HCIm were able to reduce significantly lung fibrotic changes and collagen deposition. Finally, electron microscopy revealed the presence of GNPs inside alveolar macrophages. These data support the use of GNPs locally administered in the development of new therapeutic approaches to SSc-ILD.

8.
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.

9.
RMD Open ; 4(Suppl 1): e000782, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30402270

RESUMO

Systemic sclerosis (SSc) is an orphan disease characterised by autoimmunity, fibrosis of the skin and internal organs, and vasculopathy. SSc may be associated with high morbidity and mortality. In this narrative review we summarise the results of a systematic literature research, which was performed as part of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases project, aimed at evaluating existing clinical practice guidelines or recommendations. Only in the domains 'Vascular & Ulcers' (ie, non-pharmacological approach to digital ulcer), 'PAH' (ie, screening and treatment), 'Treatment' and 'Juveniles' (ie, evaluation of juveniles with Raynaud's phenomenon) evidence-based and consensus-based guidelines could be included. Hence there is a preponderance of unmet needs in SSc referring to the diagnosis and (non-)pharmacological treatment of several SSc-specific complications. Patients with SSc experience significant uncertainty concerning SSc-related taxonomy, management (both pharmacological and non-pharmacological) and education. Day-to-day impact of the disease (loss of self-esteem, fatigue, sexual dysfunction, and occupational, nutritional and relational problems) is underestimated and needs evaluation.

10.
Rheumatology (Oxford) ; 57(57 Suppl 7): vii5-vii10, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30289535

RESUMO

TNF inhibitors are biologic DMARDs approved for the treatment of active RA in mid-1990s. They still represent a valuable therapeutic option to control the activity, disability and radiographic progression of the disease. In the context of TNF inhibitors, there are currently several molecules and different administration routes that provide optimal treatment personalization, allowing us to respond to a patient's needs in the best possible way. The increasing use of TNF inhibitors has not only improved the management of RA, but it has also helped in our understanding of the pathogenetic mechanisms of the disease. This review focuses on the basis of this targeted therapy and on the knowledge gained from their use about therapeutic effects and adverse events. Effectiveness analysed from drug registries and safety issues are presented together with recent data on infections (in particular, Mycobacterium tuberculosis and hepatitis B), cancer (lymphoma, skin cancers) and cardiovascular risk.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Previsões , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Artrite Reumatoide/diagnóstico , Progressão da Doença , Humanos
12.
Clin Exp Rheumatol ; 36 Suppl 113(4): 3-23, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30277868

RESUMO

Systemic sclerosis is a rare acquired systemic disease characterised by a complex pathogenesis and multi organ involvement. Every year the scientific world contributes to enrich the knowledge on the pathogenesis, clinical manifestations, diagnosis and treatment of this complex and severe disease. Herewith, we provide an overview of the most significant literature contributions published over the last year.


Assuntos
Escleroderma Sistêmico , Animais , Epigênese Genética , Predisposição Genética para Doença , Humanos , Fenótipo , Prognóstico , Fatores de Risco , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/terapia
13.
Mod Rheumatol ; 28(3): 542-549, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28880727

RESUMO

BACKGROUND: Treat to target (T2T), aiming at inactive disease (ID), has become the recommended strategy for axial-SpA (ax-SpA). Using the Ankylosing Spondylitis Disease Activity Score (ASDAS), we assessed the prevalence of ID in ax-SpA patients treated with TNFα inhibitors (TNFi). METHODS: A multicentric, cross-sectional study was performed assessing disease activity status (BASDAI and ASDAS) of consecutive patients with ax-SpA on stable treatment with TNFi for at least six months. We analyzed differences with nonradiographic axSpA (nr-ax-SpA) and the influence of population characteristics and comorbidities in reaching ID. ID was defined as ASDAS-CRP <1.3. RESULTS: A total of 218 patients were enrolled, 165 with AS and 53 with nr-ax-SpA. ASDAS-CRP ID was reached by 89 (40.8%) patients, while 163 (74.8%) of patients achieved good disease control with BASDAI. There were no significant differences between the two diagnostic groups. Multivariate logistic regression demonstrated a negative correlation of concomitant fibromyalgia, higher BASMI and current NSAIDs with the chances of reaching ASDAS-CRP ID or BASDAI <4. CONCLUSION: T2T represents a new challenge in the management of ax-SpA, with recently introduced disease activity measures being significantly more stringent. The prevalence of ID was affected by concomitant fibromyalgia, decreased spine mobility and concomitant NSAIDs.


Assuntos
Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Feminino , Fibromialgia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/patologia
14.
Clin Exp Rheumatol ; 36(1): 44-49, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28770709

RESUMO

OBJECTIVES: To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD). METHODS: The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2). RESULTS: 445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005). CONCLUSIONS: In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility.


Assuntos
Artrite/epidemiologia , Miosite/epidemiologia , Adulto , Artrite/diagnóstico , Artrite/imunologia , Autoanticorpos/sangue , Biomarcadores/sangue , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Miosite/diagnóstico , Miosite/imunologia , Fenótipo , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
15.
Clin Exp Rheumatol ; 35 Suppl 106(4): 3-20, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29035173

RESUMO

Systemic sclerosis is a rare acquired systemic disease characterised by heterogeneous evolution and outcome. Each year novel insights into the pathogenesis, diagnosis and treatment of this severe disease have been published. We herewith provide our overview of the most significant literature contributions published over the last year.


Assuntos
Escleroderma Sistêmico/terapia , Animais , Biomarcadores , Quimioterapia Combinada , Transplante de Células-Tronco Hematopoéticas , Humanos , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/etiologia
16.
Rheumatology (Oxford) ; 56(9): 1607-1617, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28486662

RESUMO

Objectives: Chemokines are essential contributors to leucocyte accumulation at sites of inflammatory pathology. Interfering with chemokine or chemokine receptor function therefore represents a plausible therapeutic option. However, our currently limited understanding of chemokine orchestration of inflammatory responses means that such therapies have not yet been fully developed. We have a particular interest in the family of atypical chemokine receptors that fine-tune, or resolve, chemokine-driven responses. In particular we are interested in atypical chemokine receptor 2 (ACKR2), which is a scavenging receptor for inflammatory CC-chemokines and that therefore helps to resolve in vivo inflammatory responses. The objective of the current study was to examine ACKR2 expression in common arthropathies. Methods: ACKR2 expression was measured by a combination of qPCR and immuno-histochemistry. In addition, circulating cytokine and chemokine levels in patient plasma were assessed using multiplexing approaches. Results: Expression of ACKR2 was elevated on peripheral blood cells as well as on leucocytes and stromal cells in synovial tissue. Expression on peripheral blood leucocytes correlated with, and could be regulated by, circulating cytokines with particularly strong associations being seen with IL-6 and hepatocyte growth factor. In addition, expression within the synovium was coincident with aggregates of lymphocytes, potentially atopic follicles and sites of high inflammatory chemokine expression. Similarly increased levels of ACKR2 have been reported in psoriasis and SSc. Conclusion: Our data clearly show increased ACKR2 in a variety of arthropathies and taking into account our, and others', previous data we now propose that elevated ACKR2 expression is a common feature of inflammatory pathologies.


Assuntos
Artrite Psoriásica/imunologia , Artrite Reumatoide/imunologia , Receptores de Quimiocinas/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Células Cultivadas , Quimiocinas/sangue , Citocinas/sangue , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Membrana Sinovial/imunologia
17.
Clin Exp Rheumatol ; 35(4): 660-665, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28516879

RESUMO

OBJECTIVES: Targeted drugs against key pathogenetic molecules such as TNF-alpha have significantly improved outcomes in rheumatoid arthritis (RA). They are widely used in clinical practice and drug registries give us information to support their use. Adalimumab (ADA) is able to induce a comprehensive disease control in RA by achieving clinical, functional and radiographic control. METHODS: By interrogating 2 Italian registries, LORHEN and GISEA, we analysed the efficacy of ADA in first- or second-line in a total of 2262 RA patients. RESULTS: Patients in 1st line were significantly older, with lower disease activity and HAQ scores compared to 2nd line. In 1st line, rates of DAS28-remission (DAS28rem) at 2 years were 34.4% while 26.5% in 2nd line (p=0.038). A normal HAQ score (HAQ≤0.5) was achieved in 53.5% after 2 years in 1st line versus 30.1% in 2nd (p<0.0001). DAS28rem+HAQ≤0.5, a combined parameter that we defined global clinical disease control, was reached in 20.7% in 1st line versus 13.3% in 2nd (p<0.01). Five-year-survival on therapy was higher for patients in 1st line (45.6% vs. 33.2%, p<0.0001). Discontinuation due to lack of efficacy was lower in 1st line (37.4 vs. 54.4%, p<0.0001). Rates of adverse events were similar. CONCLUSIONS: Responses in 1st line are generally significantly better than after a first anti-TNF-alpha failure but patients in 2nd line have a worse clinical and functional profile. A global disease control with clinical and functional remission is an achievable target in both lines.


Assuntos
Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Sistema de Registros , Corticosteroides/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Feminino , Humanos , Itália , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Indução de Remissão , Índice de Gravidade de Doença , Falha de Tratamento
18.
Autoimmun Rev ; 16(3): 253-257, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28147261

RESUMO

OBJECTIVE: Arthritis, myositis and interstitial lung disease (ILD) constitute the classic clinical triad of anti-synthetase syndrome (ASSD). These patients experience other accompanying features, such as Raynaud's phenomenon, fever or mechanic's hands. Most ASSD patients develop the complete triad during the follow-up. In the present study we aimed to determine whether the subsequent appearance of accompanying features may suggest the development of triad findings lacking at the onset in anti-Jo1 positive ASSD patients. METHODS: Anti-Jo1 positive patients presenting with incomplete ASSD (no >2 classic triad features) were assessed. Clinical characteristics and clusters of disease manifestations were retrospectively collected and analyzed in a large international multicenter cohort of ASSD patients. RESULTS: 165 patients (123 women) with incomplete ASSD were identified. Ninety-five patients (57.5%) developed new classic triad manifestations after 15months median (IQR 9-51) and 40 (24%) developed new accompanying features after 19months median (IQR 6-56) from disease onset. During the follow-up, the ex-novo occurrence of triad features was observed in 32 out of 40 patients (80%) with new accompanying findings and in 63 out of 125 patients (50.5%) without new accompanying findings (p=0.002). In patients with at least one new accompanying feature the odds ratio for the occurrence of new triad manifestations was 3.94 with respect to patients not developing ex-novo accompanying findings (95% CI 1.68-9.21, p=0.002). CONCLUSION: Anti-Jo1 ASSD patients with incomplete forms at disease onset are at high risk for the subsequent occurrence of lacking classic triad findings. Although all ASSD patients should be carefully assessed for the occurrence of new triad features, a closer follow-up should be considered in the subgroup of patients developing ex novo accompanying findings. These patients, indeed, have near four-fold increased risk for new classic triad manifestation occurrence with respect to patients not presenting ex novo accompanying findings.


Assuntos
Ligases/antagonistas & inibidores , Doença de Raynaud/metabolismo , Autoanticorpos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome
19.
Rheumatology (Oxford) ; 55(12): 2248-2259, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27616146

RESUMO

OBJECTIVES: Prolactin (PRL) is a lactation-inducing hormone with immunomodulatory properties and is found at elevated levels in the serum of patients with RA and other rheumatic diseases. The PRL receptor (PRLR) has been shown to be expressed by macrophages in atherosclerotic plaques. The aim of this study was to examine PRLR expression by synovial macrophages and its role in the regulation of macrophage activation. METHODS: Serum monomeric 23 kDa PRL levels were measured in 119 RA patients using a fluoroimmunometric assay. PRLR expression was assessed in synovial tissue of 91 RA, 15 PsA and 8 OA patients by immunohistochemistry and digital image analysis. Double IF was used to identify PRLR-expressing cells. The effects of PRL on monocyte-derived macrophage gene expression were examined by quantitative real-time PCR and ELISA. RESULTS: Serum PRL levels were similar in female and male RA patients. Median (interquartile range) PRLR expression was significantly higher (P < 0.05) in RA and PsA synovial tissue compared with OA. PRLR colocalized with synovial CD68+ macrophages and von Willebrand factor+ endothelial cells. In vitro, PRLR was prominently expressed in IFN-γ-and IL-10-polarized macrophages compared with other polarizing conditions. PRL by itself had negligible effects on macrophage gene expression, but cooperated with CD40L and TNF to increase expression of pro-inflammatory genes including IL-6, IL-8 and IL-12ß. CONCLUSIONS: Synovial PRLR expression is enhanced in patients with inflammatory arthritis compared with OA, and PRL cooperates with other pro-inflammatory stimuli to activate macrophages. These results identify PRL and PRLR as potential new therapeutic targets in inflammatory arthritis.


Assuntos
Artrite Psoriásica/metabolismo , Artrite Reumatoide/metabolismo , Ativação de Macrófagos/fisiologia , Receptores da Prolactina/metabolismo , Membrana Sinovial/metabolismo , Antígenos CD/metabolismo , Artrite Psoriásica/imunologia , Artrite Reumatoide/imunologia , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Membrana Sinovial/imunologia , Regulação para Cima
20.
Medicine (Baltimore) ; 95(39): e4827, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27684814

RESUMO

Among different subgroups of pulmonary arterial hypertension (PAH), those associated with connective tissue diseases (CTDs) have distinct hemodynamic and prognostic features; a correct etiologic diagnosis is thus mandatory.To estimate frequency and prognosis of previously undiagnosed CTDs in a suspect idiopathic (i) PAH cohort.Consecutive patients with PAH confirmed by right heart catheterization referred at the Cardiology Division of our Hospital without a previous rheumatological assessment or the occurrence of other conditions explaining PAH were checked for CTD by a clinical, laboratory, and instrumental evaluation. Survival in each group has also been analyzed.In our study 17 of 49 patients were classified as CTD-PAH, corresponding to a prevalence (95% CI) of 34.7% (21.7-49.6%). ANA positivity had 94% (71.3-99.9%) sensitivity and 78.1% (60-90.7%) specificity for a diagnosis of CTD-PAH; Raynaud phenomenon (RP) showed 83.3% (51.6-97.9%) sensitivity and 100% (90.5-100%) specificity for the diagnosis of Systemic Sclerosis (SSc)-PAH. At diagnosis, SSc patients were older and had a lower creatinine clearance compared with iPAH and other CTD-PAH. After a median follow-up of 44 (2-132) months, 18 of 49 (36.7%) patients died: 31.2% in the iPAH group, 20% in the CTD-, and 58.3% in the SSc-PAH group. Mortality was significantly higher in SSc-PAH (HR 3.32, 1.11-9.95, P <0.05) versus iPAH.We show a high prevalence of undiagnosed CTDs in patients with iPAH without a previous rheumatological assessment. All patients with RP were diagnosed with SSc. Our data stress the importance of a rheumatological assessment in PAH, especially because of the unfavorable prognostic impact of an associated SSc.


Assuntos
Doenças do Tecido Conjuntivo/diagnóstico , Diagnóstico Tardio/estatística & dados numéricos , Hipertensão Pulmonar/mortalidade , Doença de Raynaud/diagnóstico , Escleroderma Sistêmico/diagnóstico , Adulto , Idoso , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/epidemiologia , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Doença de Raynaud/complicações , Doença de Raynaud/epidemiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/epidemiologia , Sensibilidade e Especificidade
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