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2.
Arthritis Res Ther ; 22(1): 5, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915059

RESUMO

OBJECTIVE: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy. METHODS: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies. RESULTS: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment. CONCLUSION: While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.

3.
Neurology ; 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882529

RESUMO

OBJECTIVE: To refine the predictive significance of muscle granuloma in patients with myositis. METHODS: A group of 23 patients with myositis and granuloma on muscle biopsy (granuloma-myositis) from 8 French and Belgian centers was analyzed and compared with (1) a group of 23 patients with myositis without identified granuloma (control-myositis) randomly sampled in each center and (2) a group of 20 patients with sporadic inclusion body myositis (sIBM) without identified granuloma (control-sIBM). RESULTS: All but 2 granuloma-myositis patients had extramuscular involvement, including signs common in sarcoidosis that were systematically absent in the control-myositis and the control-sIBM groups. Almost half of granuloma-myositis patients matched the diagnostic criteria for sIBM. In these patients, other than the granuloma, the characteristics of the myopathy and its nonresponse to treatment were similar to the control-sIBM patients. Aside from 1 patient with myositis overlapping with systemic sclerosis, the remaining granuloma-myositis patients did not match the criteria for a well-defined myositis subtype, suggesting pure sarcoidosis. Matching criteria for sIBM was the sole feature independently associated with nonresponse to myopathy treatment in patients with granuloma-myositis. CONCLUSION: Patients with granuloma-myositis should be carefully screened for sIBM associated with sarcoidosis in order to best tailor their care.

4.
Front Immunol ; 10: 1263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275301

RESUMO

The lung offers one of the largest exchange surfaces of the individual with the elements of the environment. As a place of important interactions between self and non-self, the lung is richly endowed in various immune cells. As such, lung natural killer (NK) cells play major effector and immunoregulatory roles to ensure self-integrity. A better understanding of their abilities in health and diseases has been made possible over the past decade thanks to tremendous discoveries in humans and animals. By precisely distinguishing the different NK cell subsets and dissecting the ontogeny and differentiation of NK cells, both blood and tissue-resident NK populations now appear to be much more pleiotropic than previously thought. In light of these recent findings in healthy individuals, this review describes the different lung NK cell populations quantitatively, qualitatively, phenotypically, and functionally. Their identification, immunological diversity, and adaptive capacities are also addressed. For each of these elements, the impact of the mutual interactions of lung NK cells with environmental and microenvironmental factors are questioned in terms of functionality, competence, and adaptive capacities. As pulmonary diseases are major causes of morbidity and mortality worldwide, special attention is also given to the involvement of lung NK cells in various diseases, including infectious, inflammatory, autoimmune, and neoplastic lung diseases. In addition to providing a comprehensive overview of lung NK cell biology, this review also provides insight into the potential of NK cell immunotherapy and the development of targeted biologics.

5.
Autoimmun Rev ; 18(5): 476-483, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30844551

RESUMO

INTRODUCTION: Juvenile temporal arteritis (JTA) is a recently-described and little-known inflammatory disease and its etiology is undetermined. Less than forty cases have been published. This paper is aimed at reporting the largest JTA series and to compare it to literature data to better evaluate its characteristics at diagnosis, its evolution and treatment options. MATERIAL AND METHODS: We conducted a retrospective and descriptive multicentric study in France by identifying adult patients under the age of 50 which had a pathological temporal artery biopsy owing to the presence of a temporal arteritis. Patients with temporal arteritis as a manifestation of systemic vasculitis were excluded. RESULTS: We included 12 patients and the literature review identified 32 cases described in 27 articles, thus a total of 44 patients - 34 men and 10 women - with a median age of 30 and a maximum of 44. All patients presented either a lump in the temporal region or prominent temporal arteries, and 47.7% of patients suffered from headaches. Only 11.4% of patients presented general symptoms and 6.8% a biological inflammatory syndrome; 34.1% had peripheral blood eosinophilia; 83.7% presented a single episode and complete excision without further treatment was documented for 72.7%. Pathology analysis revealed infiltrate of inflammatory cells in the arterial wall in 97.6% of patients but also sparse giant cells for 25% and granuloma for 22.9%, perivascular extension of the inflammation for 82.6%, and presence of lymphoid follicles or germinal centres for 60%. Clinical relapses were present in 16.3% of cases. CONCLUSION: JTA is a rare, localized and benign disease. The majority of cases have only one episode which is cured by local surgery.


Assuntos
Arterite de Células Gigantes , Artérias Temporais/patologia , Adolescente , Adulto , Biópsia , Feminino , França/epidemiologia , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/epidemiologia , Arterite de Células Gigantes/patologia , Arterite de Células Gigantes/terapia , Cefaleia/diagnóstico , Cefaleia/etiologia , Cefaleia/terapia , Humanos , Masculino , Estudos Retrospectivos , Síndrome , Adulto Jovem
6.
J Neuromuscul Dis ; 6(1): 99-107, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30714969

RESUMO

BACKGROUND: Manual muscle testing has been widely used for the evaluation of muscle strength in myositis, yet less attention has been devoted to the evaluation of muscle function and endurance. OBJECTIVE: Our objective was therefore to compare the responsiveness to change of muscle strength, endurance and functional testing following induction therapy for severe myositis flare (requiring high-dose corticosteroids and combined immunotherapy) in patients with a diagnosis of dermatomyositis, immune-mediated necrotizing myopathy, or overlap myositis. METHODS: Muscle status was assessed at baseline and after mean 6.4±1.9 months, using the MRC-5 scale, along with endurance (Barre and Mingazzini maneuvers) and functional evaluation (e.g. chair rise) and responsiveness to change was evaluated using the Standardized Response Mean (SRM) and Standardized Mean Difference. RESULTS: Among the 49 patients included, the strongest responsiveness to change was observed in the muscle testing of the psoas and deltoids (SRM: 1.23 and 1.16, respectively). Noticeably, endurance testing also demonstrated strong responsiveness (SRM: 1.05 and 0.96, respectively), compensating for the poor discriminatory ability of muscle testing and permitting to overcome its ceiling effect. CONCLUSION: Functional and endurance testing provide simple and reliable measures complementing the testing of select proximal muscle groups to evaluate responsiveness to intervention in myositis patients in daily clinical practice. Interest of functional and endurance testing should be evaluated prospectively as outcome measures in myositis clinical trials.


Assuntos
Força Muscular , Miosite/diagnóstico , Resistência Física , Corticosteroides/uso terapêutico , Adulto , Estudos de Coortes , Teste de Esforço , Feminino , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Miosite/fisiopatologia , Miosite/terapia , Reprodutibilidade dos Testes
8.
J Rheumatol ; 46(6): 623-627, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30554155

RESUMO

OBJECTIVE: A pathogenic role of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies has been proposed. Our objective was to assess efficacy of rituximab (RTX) in anti-HMGCR immune-mediated necrotizing myopathy. METHODS: All patients who had been treated with RTX were retrospectively reviewed to assess features and outcome. RESULTS: Three of 9 patients demonstrated stable or improved muscle strength ± decline in creatine kinase levels, or T2/short-tau inversion recovery hypersignal decrease on magnetic resonance imaging following RTX treatment. RTX permitted intravenous immunoglobulin discontinuation and corticosteroid reduction to low dose in 2 patients. CONCLUSION: One-third of patients with refractory anti-HMGCR had improved strength or other evidence of improved disease activity following RTX treatment.

9.
Expert Rev Anticancer Ther ; 19(3): 209-222, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30572735

RESUMO

INTRODUCTION: Immune checkpoint inhibitors (ICI) are now a standard of care in the treatment of many cancers leading to durable responses in patients with metastatic disease. These agents are generally well tolerated but may lead to the occurrence of immune-related adverse events (irAEs). As any organ may be affected, clinicians should be aware of the broad range of clinical manifestations and symptoms and keep in mind that toxicities may occur late, at any point along a patient's treatment course. Although the most common irAEs are rarely severe, some of them may be associated with great morbidity and even become life-threatening. The rate of occurrence, type and severity of irAEs may vary with the type of ICI; thus, grade 3 and 4 irAEs are reported in more than 55% of patients treated with the combination of ipilimumab 3 mg/kg and nivolumab 1 mg/kg. Area covered: This review presents the management of irAEs resulting from checkpoint blockade, with a focus on rare irAEs. Expert commentary: With the development of immuno-oncology and the expanding role of ICI, physicians have learnt to diagnose and treat most of the irAEs that can occur. This review provides an overview of current guidelines, previously published studies and our multidisciplinary team based practices.

10.
Curr Opin Rheumatol ; 30(6): 664-673, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30239350

RESUMO

PURPOSE OF REVIEW: Antisynthetase syndrome (ASyS) is an acquired myopathy characterized by the presence of myositis-specific autoantibodies directed against tRNA-synthetases. ASyS is potentially life threatening due to lung involvement and treatment remains a challenge to date. With symptoms not limited to muscles but also involving lung, skin and joints, ASyS appears specific and has a particular pathogenesis, different from the other inflammatory myopathies. This review is intended to discuss the current understanding of ASyS pathogenesis, pointing its current knowledge and also the crucial prospects that may lead to critical improvement of ASyS care. RECENT FINDINGS: Regarding ASyS pathogenesis, initiation of the disease seems to arise in a multifactorial context, with first lesions occurring within the lungs. This may lead to aberrant self-antigen exposure and tolerance breakdown. The consequences are abnormal activation of both innate and adaptive immunity, resulting in the patients with favourable genetic background to autoimmune-mediated organ lesions. Immune and nonimmune roles of the antigen, as well as antigen presentation leading to specific T-cell and B-cell activation and to the production of specific autoantibodies belong to the disease process. SUMMARY: This work aims to detail ASyS pathogenesis understanding, from initiation to the disease propagation and target tissue lesions, in order to considering future treatment directions.


Assuntos
Imunidade Adaptativa , Autoanticorpos/imunologia , Autoantígenos/imunologia , Miosite/imunologia , Humanos
11.
Neurology ; 91(10): e985-e994, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30089619

RESUMO

OBJECTIVE: To report the clinicopathologic features and outcome of myositis in patients treated with immune checkpoint inhibitors (ICIs) (irMyositis). METHODS: We retrospectively analyzed patients diagnosed with irMyositis in tertiary centers in Paris, France, and Berlin, Germany, from January 2015 to July 2017. The main outcomes were clinical manifestations and muscle histology, which included major histocompatibility complex class I (MHC-I), C5b-9, CD3, CD4, CD8, CD20, CD68, programmed cell death protein 1 (PD-1), programmed cell death 1 ligand 1 (PD-L) 1, and programmed cell death 1 ligand 2 (PD-L2). RESULTS: Ten patients with metastatic cancer were included; median age was 73 (range 56-87) years. Median follow-up duration was 48 (range 16-88) weeks. Six patients developed myositis during nivolumab therapy, 1 patient during pembrolizumab, 1 patient during durvalumab, and 2 patients during combined nivolumab and ipilimumab. Median delay between ICI initiation and myositis onset was 25 (range 5-87) days. Clinical manifestations were dominated by acute or subacute myalgia (8 patients) and limb-girdle (7), axial (7), and oculomotor (7) weakness. Four patients had evidence of myocarditis. In all patients, creatine kinase levels were elevated (median 2,668, range 1,059-16,620 U/L), while anti-acetylcholine receptor and myositis-associated antibodies were negative. Electrodiagnostic studies showed myopathic process without decrement in all patients. Muscle biopsy constantly showed multifocal necrotic myofibers, sarcolemmal MHC-I, and endomysial inflammation, consisting mainly of CD68+ cells expressing PD-L1 and CD8+ cells expressing PD-1. ICI treatment was withdrawn in all patients; 9 patients received immunosuppressive therapy, which consistently led to marked clinical improvement. CONCLUSIONS: irMyositis presents with remarkably homogeneous and unique clinicopathologic features, expanding the nosologic spectrum of inflammatory myopathies in patients with cancer. ICI withdrawal and treatment with corticosteroids improve outcome.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Citocinas/metabolismo , Miocardite/etiologia , Miosite/etiologia , Neoplasias/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Creatina Quinase/metabolismo , Eletromiografia , Europa (Continente) , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Miocárdio/patologia , Miosite/diagnóstico por imagem , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Estudos Retrospectivos , Adulto Jovem
12.
J Rheumatol ; 45(9): 1296-1300, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29961694

RESUMO

OBJECTIVE: To investigate the uncommon co-occurrence of antisynthetase syndrome (AS) and sarcoidosis. METHODS: From 2000 to 2015, patients with sarcoidosis were extracted from a retrospective multicentric cohort of 352 patients with AS. RESULTS: Ten patients (2.8%; 6 men, 8 whites, 5 smokers, median age 50 yrs) had both AS and sarcoidosis. Most of the time, sarcoidosis and AS occurred simultaneously (n = 7). Antibody testing revealed anti-Jo1 (n = 5), anti-PL12 (n = 4), or anti-PL7 (n = 1). Finally, no patient had a worsening of muscular condition, 5 patients presented respiratory deterioration, 3 remained stable, and 2 showed improvement. CONCLUSION: Sarcoidosis may be underdiagnosed in patients with AS.


Assuntos
Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Miosite/complicações , Sarcoidose/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Estudos Retrospectivos , Sarcoidose/sangue
13.
Neurol Neuroimmunol Neuroinflamm ; 5(3): e452, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29845092

RESUMO

Objectives: To describe clinicopathologic features of muscular sarcoidosis and the associated sarcoidosis phenotype through a nationwide multicenter study. Methods: Patients were included if they had histologically proven sarcoidosis and symptomatic muscular involvement confirmed by biological, imaging, or histologic examinations. Results: Forty-eight patients (20 males) were studied, with a median age at muscular symptoms onset of 45 years (range 18-71). Four patterns were identified: a nodular pattern (27%); smoldering phenotype (29%); acute, subacute, or progressive myopathic type (35%); and combined myopathic and neurogenic pattern (10%). In all patterns, sarcoidosis was multivisceral with a median of 3 extramuscular organs involved (mostly lungs, lymph nodes, eyes, and skin) and a prolonged course with long-term use of corticosteroids and immunosuppressive drugs. Muscular patterns differed according to clinical presentation (myalgia, nodules, or weakness), electromyographic findings, muscular MRI, and response to sarcoidosis treatment. The myopathic and neuromuscular patterns were more severe. Conclusion: This nationwide study of muscular sarcoidosis allowed the identification of 4 patterns of granulomatous myositis, which differed by phenotypes and the clinical course.

14.
J Neurol ; 265(4): 757-763, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29392458

RESUMO

OBJECTIVES: Takayasu arteritis (TA) is a giant cell arteritis usually affecting young women and characterized by inflammatory and ischemic signs of large vessel involvement, including extracranial cerebral arteries. The impact of stroke on TA prognosis has not been well evaluated. METHODS: We performed a retrospective multicenter review of patients with definite TA who experienced at least one stroke and compared the findings to 17 matched patients with TA diagnosis without neurological involvement. RESULTS: Seventeen patients (15 women, median age at stroke diagnosis 44 years) receiving a diagnosis of TA and stroke between 2002 and 2016 in our institution were included, from a cohort of 126 patients suffering from TA (13.5%). At diagnosis, patients from both groups had comparable cardiovascular risk factors. The first cerebrovascular event was ischemic stroke (n = 15) or transient ischemic attack (n = 2). In eight patients, stroke occurred after the TA diagnosis was made. In four patients, stroke occurred after carotid surgery. At the end of follow-up, 59% of patients had a neurological impairment, 35% had a recurrence of stroke, and 24% suffered from epilepsy. CONCLUSIONS: Stroke is a major cause of disability in TA patients. Internal carotid surgery may be performed with caution because of the risk of stroke after the procedure.


Assuntos
Ataque Isquêmico Transitório/etiologia , Acidente Vascular Cerebral/etiologia , Arterite de Takayasu/complicações , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Transtornos Cognitivos/etiologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Ataque Isquêmico Transitório/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Arterite de Takayasu/tratamento farmacológico , Adulto Jovem
16.
Crit Rev Immunol ; 38(4): 263-278, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30806243

RESUMO

Among the inflammatory myopathies, anti-tRNA-synthetase syndrome (ASyS) is a severe autoimmune condition characterized by extramuscular involvement, affecting especially the lungs. ASyS specific serological markers are anti-tRNA-synthetase autoantibodies, among which anti-histidyl-tRNA-synthetase is the most common. In the past decades, ASyS has been distinguished by unique histological features attributed to a specific pathogenesis. Research has highlighted the role of environmental factors and infections as possible triggers. Tissue modifications of histidyl-tRNA-synthetase (HisRS) expression might be responsible for the recruitment and activation of both innate and adaptive immune cells. HisRS not only acts through antigenic properties, but also through many others, including chemoattraction, innate pathway activation, and cytokine-like functions. Favored by a certain genetic background, this whole activation of immunity results in widespread and specific tissue damage and finally leads to visible heterogeneous symptoms characterizing the disease state. Understanding the pathogenesis of ASyS is essential to improving patient care by identifying biomarkers and designing new therapeutic strategies accordingly. Therefore, this review details the recent hypotheses concerning the dynamic of ASyS pathogenesis with the aim of enlightening the development of new therapeutic axes in the future.


Assuntos
Miosite/imunologia , Miosite/patologia , Animais , Histidina-tRNA Ligase/biossíntese , Histidina-tRNA Ligase/imunologia , Histidina-tRNA Ligase/metabolismo , Humanos , Miosite/genética
17.
Blood ; 130(8): 1007-1013, 2017 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-28679734

RESUMO

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that most commonly affects adults and is driven by a high frequency of mutations in BRAF, MAP2K1, and kinases promoting MAPK signaling. Because of the relative rarity of ECD, key clinical features of the disease may not be well defined. Across a multi-institutional cohort of 189 patients with ECD and ECD overlapping with Langerhans cell histiocytosis (so-called mixed histiocytosis [MH]), we identified an unexpected and heretofore undescribed frequent occurrence of myeloid neoplasms among patients with ECD and MH. Some 10.1% (19/189) of patients with ECD have an overlapping myeloid neoplasm, most commonly occurring as a myeloproliferative neoplasm (MPN), myelodysplastic syndrome (MDS), or mixed MDS/MPN overlap syndrome (including chronic myelomonocytic leukemia). Consistent with this, molecular analysis frequently detected hallmark driver mutations of myeloid neoplasms (such as JAK2V617F and CALR mutations) coexisting with those characteristic of histiocytosis (such as BRAFV600E and MAP2K1 mutations). Histiocytosis patients diagnosed with a concomitant myeloid malignancy were significantly older at diagnosis and more commonly presented with MH than those without a myeloid malignancy. In some cases, the presence of distinct kinase mutations in the histiocytosis and myeloid neoplasm resulted in discordant and adverse responses to kinase-directed targeted therapies. These data highlight the clinical importance of evaluating adults with histiocytosis for a concomitant myeloid neoplasm.


Assuntos
Neoplasias da Medula Óssea/complicações , Neoplasias da Medula Óssea/epidemiologia , Histiocitose de Células não Langerhans/complicações , Adulto , Idoso , Doença de Erdheim-Chester/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Prevalência
19.
J Rheumatol ; 44(1): 24-32, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28042125

RESUMO

OBJECTIVE: Cardiac involvement during systemic lupus erythematosus (SLE) may include the pericardium, myocardium, valvular tissue, and coronary arteries. The aim of this study was to describe the clinical, biological, and radiological presentation of lupus myocarditis (LM) as well as the treatment response and longterm outcomes. METHODS: We conducted a multicentric retrospective study of LM from January 2000 to May 2014. RESULTS: Twenty-nine patients (3 men and 26 women) fulfilled the inclusion criteria (median age at the diagnosis of SLE: 30 yrs, range 16-57). Myocarditis was the first sign of SLE in 17/29 cases (58.6%). Troponin was elevated in 20/25 cases. Electrocardiogram results were abnormal in 25/28 cases. Echocardiography revealed low (≤ 45%) left ventricular ejection fraction (LVEF; 19/29, 66%) and pericardium effusion (20/29, 69%). Cardiac magnetic resonance imaging revealed delayed gadolinium enhancement in 9/13 patients (69%). Patients were treated with corticosteroids (n = 28), cyclophosphamide (CYC; n = 16), intravenous immunoglobulins (n = 8), and/or mycophenolate mofetil (n = 2). The median followup was 37 months. One month after the beginning of the treatment, 10/23 patients (43%) who had undergone echocardiography had an LVEF ≥ 55%. At the end of followup, 21/26 patients (81%) exhibited an LVEF ≥ 55%. Three patients died during followup, and 2 died from LM. CONCLUSION: LM is a severe manifestation of SLE. It can be the first manifestation of the disease or it can occur during followup, in particular in untreated patients. However, the longterm prognosis is typically positive. Patients with less severe disease exhibited good LVEF recovery without CYC.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Miocardite/diagnóstico , Miocardite/etiologia , Adolescente , Corticosteroides/uso terapêutico , Adulto , Ciclofosfamida/uso terapêutico , Ecocardiografia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Miocardite/tratamento farmacológico , Estudos Retrospectivos , Avaliação de Sintomas , Resultado do Tratamento , Adulto Jovem
20.
J Immunol ; 197(5): 1621-30, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27511738

RESUMO

Antisynthetase syndrome (aSS) is characterized by the association of interstitial lung disease and myositis with anti-tRNA synthetase autoantibodies. Immune mechanisms leading to aSS could be initiated in the lungs, but the role of NK cells has not yet been studied. Both extensive NK cell phenotype and functions were compared between 33 patients and 26 controls. Direct and redirected polyfunctionality assays (degranulation and intracellular production of TNF-α and IFN-γ) were performed spontaneously or after IL-12 plus IL-18 stimulation in the presence of K562 or P815 target cells, respectively. NK cells from inactive patients showed normal phenotype, whereas active aSS revealed a differentiated NK cell profile, as indicated by increased CD57 and Ig-like transcript 2 and an inability to produce IFN-γ (p = 0.002) compared with controls. Importantly, active aSS was more specifically associated with a significant NKp30 decrease (p = 0.009), although levels of mRNA and intracellular protein were similar in aSS and healthy controls. This NKp30 decrease was strongly correlated with reduced NK cell polyfunctionality in both direct and redirected killing assays with anti-NKp30 Abs (p = 0.009 and p = 0.03, respectively), confirming its important impact in aSS. Histological studies revealed massive infiltrations of NK cells inside the lungs of aSS patients (148 versus 11/mm(2)). Taken together, these data suggest that NK cells and NKp30 could play a role in aSS pathogenesis.


Assuntos
Células Matadoras Naturais/imunologia , Miosite/imunologia , Receptor 3 Desencadeador da Citotoxicidade Natural/metabolismo , Adulto , Idoso , Antígenos CD57/genética , Feminino , Granzimas , Humanos , Interferon gama/biossíntese , Interferon gama/imunologia , Interleucina-12/sangue , Interleucina-12/imunologia , Interleucina-18/sangue , Interleucina-18/imunologia , Células K562 , Pulmão/imunologia , Pulmão/patologia , Doenças Pulmonares Intersticiais/imunologia , Masculino , Pessoa de Meia-Idade , Miosite/fisiopatologia , Receptor 3 Desencadeador da Citotoxicidade Natural/genética , Fenótipo , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
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