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1.
Artigo em Inglês | MEDLINE | ID: mdl-33769468

RESUMO

OBJECTIVES: Study aim was to evaluate estimated glomerular filtration rate (eGFR), its association with clinical disease and its predictive ability with mortality in systemic sclerosis (SSc) patients from the European Scleroderma Trials and Research Group (EUSTAR) database. METHODS: SSc patients from the EUSTAR database with available items for calculation of eGFR at baseline visit and with a second follow-up visit were included. A cut-off of 60 ml/min was chosen for all SSc patients and 30 ml/min for scleroderma renal crisis (SRC). Cox regression and competing risk analysis were performed to evaluate the role of eGFR as predictive factor of mortality. RESULTS: 3650 SSc patients were included. Mean serum level of creatinine and eGFR were 0.8 mg/dl (IQR 0.6-0.9) and 86.6 ± 23.7 ml/min. The eGFR was significantly lower in patients with pulmonary hypertension. Overall survival (OS) was significantly reduced in SSc patients with eGFR <60 ml/min respect to patients with eGFR ≥ 60 ml/min [OS at five years 0.763 (CI 95%: 0.700-0.814) vs 0.903 (CI 95%: 0.883-0.919 p< 0.001)]. In multivariable analysis, OS was associate with male gender (p< 0.01), systolic pulmonary arterial pressure (sPAP) (p< 0.001) and eGFR (p< 0.001). Cumulative incidence of deaths due to SSc was associate with increased sPAP (p< 0.001) and reduced eGFR (p< 0.05). OS at five years of 53 SRC patients was not significantly different in SSc patients with eGFR > 30 ml/min or eGFR < 30 ml/min. CONCLUSION: eGFR represents a predictive risk factor of overall survival in SSc. The eGFR is not a risk factor for death in SRC.

2.
Best Pract Res Clin Rheumatol ; : 101672, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33745826

RESUMO

Systemic sclerosis is an autoimmune disease that prominently leads to skin and tissue fibrosis. The efficacy of autologous stem cell transplantation not only attests to the autoimmune pathophysiology for systemic sclerosis, but also for interstitial lung disease as its most frequent manifestation of fatal organ involvement. Accordingly, a variety of immunomodulatory therapies were tried on patients with systemic sclerosis-interstitial lung disease. Until very recently, all of these therapeutic approaches constituted off-label treatment for systemic sclerosis, given that neither of these therapies was approved by the United States Food and Drug Administration (FDA) or the European Medicines Agency. For tocilizumab, this has now changed with FDA approval in March 2021. Already 2020, nintedanib, which is an antifibrotic drug that does not target autoimmunity, became the first approved drug for interstitial lung disease in systemic sclerosis. The present review analyzes the evidence for immunomodulatory treatment of systemic sclerosis-associated interstitial lung disease. The review focuses on randomized controlled trials, which provides evidence for the effects of drugs such as cyclophosphamide, mycophenolate, rituximab and tocilizumab.

3.
Mol Immunol ; 131: 112-120, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33446393

RESUMO

BACKGROUND: Networks formed of numerous autoantibodies (aabs) directed against G-protein coupled receptors (GPCR) have been suggested to play important role in autoimmune disorders. In present study, we aimed to evaluate the association between anti-GPCR antibodies and primary Sjogren's syndrome (pSS) to determine the potential pathogenic factors. METHODS: By applying a cell membrane-based ELISA technique, which is capable of detecting aabs against conformational epitopes within GPCR, serum levels of fourteen GPCR were determined in well-characterized patients with pSS (n = 52) and gender-matched healthy controls (n = 54). Comparisons between groups were analyzed by two-tailed Mann-Whitney U test, Bonferroni correction was applied for multiple comparisons. Spearman`s rank correlation coefficients were calculated between variables and visualized by heat map. RESULTS: Compared to healthy subjects, sera of patients with pSS showed significantly higher binding to ß2AR and ETAR, but lower binding to C5aR1, C3aR1, CXCR3, and CXCR4. Autoantibodies against C5aR1, C3aR1, CXCR3, and CXCR4 were also decreased in patients with rheumatoid arthritis. In pSS patients, levels of anti-CXCR3 and anti-CXCR4 antibodies were negatively correlated with circulating lymphocyte counts. Furthermore, correlation signatures of anti-GPCR antibodies changed dramatically in the patients with pulmonary involvement. CONCLUSIONS: This study demonstrates an association between pSS and autoantibodies recognizing GPCR, especially those functionally involved in immune cell migration and exocrine glandular secretion.


Assuntos
Autoanticorpos/imunologia , Receptor da Anafilatoxina C5a/imunologia , Receptores CXCR3/imunologia , Receptores CXCR4/imunologia , Receptores de Complemento/imunologia , Síndrome de Sjogren/imunologia , Adulto , Idoso , Animais , Artrite Reumatoide/imunologia , Células CHO , Estudos de Casos e Controles , Cricetulus , Feminino , Humanos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade
4.
Z Rheumatol ; 80(1): 69-72, 2021 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-33340058

RESUMO

In the last few years, several studies emerged for the treatment of interstitial lung disease (ILD) associated with systemic sclerosis (SSc). Some of the studied drugs showed efficacy compared to placebo or to a control group. Since early 2020, nintedanib has been approved for the treatment of SSc-ILD. Although several drugs are used to treat SSc-LD, it is now the first approved drug for SSc-ILD. Here, we aim to provide an overview about our current therapy algorithm and strategy as well as our interpretation of study results as an experienced SSc-ILD center.


Assuntos
Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/tratamento farmacológico
5.
Sci Rep ; 10(1): 21312, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277543

RESUMO

In the search for anti-renal autoreactivity in human lupus nephritis, we stimulated blood-derived CD4+ T cells from patients with systemic lupus erythematosus with various kidney lysates. Although only minor responses were detectable, these experiments led to the development of a search algorithm that combined autoantibody association with human lupus nephritis and target gene expression in inflamed kidneys. Applying this algorithm, five potential T cell antigens were identified. Blood-derived CD4+ T cells were then stimulated with these antigens. The cells were magnetically enriched prior to measurement with flow cytometry to facilitate the detection of very rare autoantigen-specific cells. The detected responses were dominated by IFN-γ-producing CD4+ T cells. Additionally, IL-10-producing CD4+ T cells were found. In a next step, T cell reactivity to each single antigen was independently evaluated with T cell libraries and [3H]-thymidine incorporation assays. Here, Vimentin and Annexin A2 were identified as the main T cell targets. Finally, Vimentin reactive T cells were also found in the urine of three patients with active disease. Overall, our experiments show that antigen-specific CD4+ T cells targeting renally expressed antigens arise in human lupus nephritis and correlate with disease activity and are mainly of the Th1 subset.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33230552

RESUMO

OBJECTIVES: Functional IgG autoantibodies against diverse G protein-coupled receptors, i.e. antibodies with agonistic or antagonistic activity at these receptors, are abundant in human serum. Their levels are altered in patients with SSc, and autoantibodies against angiotensin II receptor 1 (ATR1) and endothelin receptor A (ETA) have been suggested to drive SSc by inducing the chemokines CXCL8 and CCL18 in the blood. The objective of our study is to profile the effect of IgG in SSc (SSc-IgG) on the production of soluble mediators in monocytic cells. METHODS: Monocyte-like THP-1 cells were stimulated with SSc-IgG and their secretome was analysed. Furthermore, the significance of major pro-inflammatory pathways for the induction of CXCL8 and CCL18 in response to SSc-IgG was assessed by a pharmacological approach. RESULTS: Stimulation with SSc-IgG significantly alters the secretome of THP-1 cells towards a general pro-inflammatory and profibrotic phenotype, which includes an increase of CCL18 and CXCL8. The consequent expression profiles vary depending on the individual donor of the SSc-IgG. CCL18 and CXCL8 expression is thus regulated differentially, with AP-1 driving the induction of both CCL18 and CXCL8 and the TAK/IKK-ß/NF-κB pathway and ERK1/2 driving that of CXCL8. CONCLUSIONS: Our results suggest that SSc-IgG contributes to the generation of the pro-inflammatory/profibrotic tissue milieu characteristic of SSc by its induction of a respective phenotype in monocytes. Furthermore, our results highlight AP-1 as a critical regulator of gene transcription of CCL18 in monocytic cells and as a promising pharmacological therapeutic target for the treatment of SSc.

8.
Ann Rheum Dis ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32988845

RESUMO

OBJECTIVES: To identify overall disease course, progression patterns and risk factors predictive for progressive interstitial lung disease (ILD) in patients with systemic sclerosis-associated ILD (SSc-ILD), using data from the European Scleroderma Trials And Research (EUSTAR) database over long-term follow-up. METHODS: Eligible patients with SSc-ILD were registered in the EUSTAR database and had measurements of forced vital capacity (FVC) at baseline and after 12±3 months. Long-term progressive ILD and progression patterns were assessed in patients with multiple FVC measurements. Potential predictors of ILD progression were analysed using multivariable mixed-effect models. RESULTS: 826 patients with SSc-ILD were included. Over 12±3 months, 219 (27%) showed progressive ILD: either moderate (FVC decline 5% to 10%) or significant (FVC decline >10%). A total of 535 (65%) patients had multiple FVC measurements available over mean 5-year follow-up. In each 12-month period, 23% to 27% of SSc-ILD patients showed progressive ILD, but only a minority of patients showed progression in consecutive periods. Most patients with progressive ILD (58%) had a pattern of slow lung function decline, with more periods of stability/improvement than decline, whereas only 8% showed rapid, continuously declining FVC; 178 (33%) experienced no episode of FVC decline. The strongest predictive factors for FVC decline over 5 years were male sex, higher modified Rodnan skin score and reflux/dysphagia symptoms. CONCLUSION: SSc-ILD shows a heterogeneous and variable disease course, and thus monitoring all patients closely is important. Novel treatment concepts, with treatment initiation before FVC decline occurs, should aim for prevention of progression to avoid irreversible organ damage.

10.
Sci Rep ; 10(1): 15931, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985601

RESUMO

Several studies reported a central role of the endothelin type A receptor (ETAR) in tumor progression leading to the formation of metastasis. Here, we investigated the in vitro and in vivo anti-tumor effects of the FDA-approved ETAR antagonist, Ambrisentan, which is currently used to treat patients with pulmonary arterial hypertension. In vitro, Ambrisentan inhibited both spontaneous and induced migration/invasion capacity of different tumor cells (COLO-357 metastatic pancreatic adenocarcinoma, OvCar3 ovarian carcinoma, MDA-MB-231 breast adenocarcinoma, and HL-60 promyelocytic leukemia). Whole transcriptome analysis using RNAseq indicated Ambrisentan's inhibitory effects on the whole transcriptome of resting and PAR2-activated COLO-357 cells, which tended to normalize to an unstimulated profile. Finally, in a pre-clinical murine model of metastatic breast cancer, treatment with Ambrisentan was effective in decreasing metastasis into the lungs and liver. Importantly, this was associated with a significant enhancement in animal survival. Taken together, our work suggests a new therapeutic application for Ambrisentan in the treatment of cancer metastasis.

11.
Kidney Int ; 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32592813

RESUMO

Systemic lupus erythematosus is a systemic and chronic autoimmune disease characterized by loss of tolerance towards nuclear antigens with autoreactive CD4+ T cells implicated in disease pathogenesis. However, very little is known about their receptor specificity since the detection of human autoantigen specific CD4+ T cells has been extremely challenging. Here we present an analysis of CD4+ T cells reactive to nuclear antigens using two complementary methods: T cell libraries and antigen-reactive T cell enrichment. The frequencies of nuclear antigen specific CD4+ T cells correlated with disease severity. These autoreactive T cells produce effector cytokines such as interferon-γ, interleukin-17, and interleukin-10. Compared to blood, these cells were enriched in the urine of patients with active lupus nephritis, suggesting an infiltration of the inflamed kidneys. Thus, these previously unrecognized characteristics support a role for nuclear antigen-specific CD4+ T cells in systemic lupus erythematosus.

12.
Rheumatology (Oxford) ; 59(11): 3380-3389, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32333004

RESUMO

OBJECTIVES: Systemic sclerosis is a heterogeneous, multisystem disease. It can occur at any age, but most patients develop the disease between the age of 40 to 50 years. There is controversial evidence on whether/how the age at disease onset affects their clinical phenotype. We here investigate the relationship between age at disease onset and symptoms in a large cohort of SSc patients (lcSSc, dcSSc and SSc-overlap syndromes). METHODS: Clinical data of the registry of the German Network for Systemic Scleroderma including 3281 patients were evaluated and subdivided into three age groups at disease onset (<40 years, 40-60 years, >60 years). RESULTS: Among all SSc patients, 24.5% developed their first non-Raynaud phenomenon symptoms at the age <40 years, and 22.5% were older than 60 years of age. In particular, older patients at onset developed the lcSSc subset significantly more often. Furthermore, they had pulmonary hypertension more often, but digital ulcerations less often. Remarkably, the course of the disease was more rapidly progressing in the older cohort (>60 years), except for gastrointestinal and musculoskeletal involvement. No significant difference was found for the use of corticosteroids. However, significantly, fewer patients older than 60 years received immunosuppressive treatment. CONCLUSION: In this large registry, ∼25% of patients developed SSc at an age above 60 years with an increased frequency of lcSSc. In this age group, an onset of internal organ involvement was significantly accelerated across all three subsets. These findings suggest that, in the elderly cohort, more frequent follow-up examinations are required for an earlier detection of organ complications.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32099344

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease leading to irreversible airflow limitation and is characterized by chronic pulmonary inflammation, obstructive bronchiolitis and emphysema. Etiologically, COPD is mediated by toxic gases and particles, eg, cigarette smoke, while the pathogenesis of the disease is largely unknown. Several lines of evidence indicate a link between COPD and autoimmunity but comprehensive studies are lacking. Methods: By using a protein microarray assaying more than 19,000 human proteins we determined in this study the autoantibody profiles of COPD and non-COPD smokers. The discovery cohort included 5 COPD patients under acute exacerbation (AECOPD) and 5 age- and gender-matched non-COPD smokers. One putative candidate autoantibody, anti-lactoferrin IgG, was further investigated by using immunoblotting with a large validation cohort containing 124 healthy controls, 92 patients with AECOPD and 52 patients with stable COPD. Results: We show that i) autoantigens targeted by autoantibodies with higher titers in COPD patients were enriched in extracellular regions, while those with lower titers in COPD patients were enriched in intracellular compartments. ii) levels of IgG autoantibodies against many neutrophil granule proteins were significantly higher in COPD patients than in non-COPD smokers. Furthermore, increased levels of anti-lactoferrin antibodies in COPD patients were confirmed in a cohort with a large number of samples. Conclusion: The comprehensive autoantibody profiles from COPD patients established in this study demonstrated for the first time a shift in the cellular localization of antigens targeted by autoantibodies in COPD.

14.
Autoimmun Rev ; 19(2): 102452, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838157

RESUMO

OBJECTIVES: Limited cutaneous systemic sclerosis (LcSSc) is the most common subset of SSc but it has been overlooked in the past years. At a time at which clinical trials focus on diffuse cutaneous SSc (DcSSc) we aimed at clarifying the outcomes of LcSSc and at evaluating whether potential drug positioned in DcSSc may also be used in LcSSc. METHODS: The EUSTAR database was used to investigate skin, lung and peripheral vasculopathy outcomes in LcSSc. Worsening of skin fibrosis, ILD and peripheral vasculopathy were defined by an increase in modified Rodnan skin score (mRSS) > 3.5 points, a decrease of FVC > 10% in patients with ILD at baseline, and by the development of new digital ulcers (DU) in patients without DU at baseline. RESULTS: 8013 LcSSc and 4786 DcSSc patients were included. In contrast to DcSSc, skin disease was remarkably stable in the majority of LcSSc patients with >80% having a change lower than ±4 units of mRSS at 12, 24 and 36 months follow-up. Conversely, FVC changes over time were very similar between LcSSc and DcSSc. Regarding DU, numbers of patients with new DU over time seemed to be almost similar between the two subsets. CONCLUSIONS: LcSSc patients have a low mRSS at baseline with marginal changes with time. Conversely, SSc-ILD can be as progressive as in DcSSc supporting the inclusion of LcSSc patients in SSc-ILD trials and suggesting potential benefit of any anti-ILD drugs. Similarly, although slightly less common, DU should receive the same attention in the two subsets.


Assuntos
Bases de Dados Factuais , Esclerodermia Limitada/epidemiologia , Feminino , Fibrose/patologia , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/patologia , Esclerodermia Limitada/tratamento farmacológico , Esclerodermia Limitada/patologia , Pele/patologia
15.
J Rheumatol ; 47(2): 241-248, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30936287

RESUMO

OBJECTIVE: Scleroderma renal crisis (SRC) is a severe life-threatening manifestation in patients with systemic sclerosis (SSc). However, the knowledge about risk factors for SRC is limited. We determined here the frequency of SRC and identified risk factors for the prediction of SRC. METHODS: Based on regular followup data from the German Network for Systemic Scleroderma, we used univariate and multivariate generalized estimating equations to analyze the association between clinical variables, SSc subsets, therapy [i.e., angiotensin-converting enzyme inhibitors (ACEi), corticosteroids], and the occurrence of SRC. RESULTS: Data of 2873 patients with 10,425 visits were available for analysis with a mean number of registry visits of 3.6 ± 2.8 and a mean time of followup of 3.6 ± 3.8 years. In total, 70 patients developed SRC (70/2873, 2.4%). Of these patients, 57.1% (40/70) were diagnosed with diffuse cutaneous SSc, 31.4% (22/70) with limited cutaneous SSc, and 11.4% (8/70) with SSc-overlap syndromes. Predictive independent factors with the highest probability for SRC were positive anti-RNA polymerase antibodies (RNAP), a history of proteinuria prior to SRC onset, diminished DLCO, and a history of hypertension. Interestingly, positive antitopoisomerase autoantibodies did not predict a higher risk for SRC. Further, patients with SRC were significantly more frequently treated with ACEi and corticosteroids without being independently associated with SRC. CONCLUSION: In this cohort, SRC has become a rare complication. By far the highest risk for SRC was associated with the detection of anti-RNAP and proteinuria.

16.
Front Immunol ; 11: 564526, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33384684

RESUMO

Expressions of G protein-coupled receptors (GPCR) on immune and tissue resident cells are the consequence of the cellular environment, which is highly variable. As discussed here, antibodies directed to GPCR (GPCR abs), their levels and correlations to other abs, serve as biomarkers for various diseases. They also could reflect the individual interplay between the environment and the immune system. Thus, GPCR abs could display pathogenic chronic conditions and could help to identify disease-related pathways. Moreover, by acting as ligands to their corresponding receptors, GPCR abs modulate autoimmune as well as non-autoimmune diseases. This article introduces GPCR abs as drivers for diseases by their capability to induce a specific signaling and by determining immune cell homeostasis. The identification of the individual GPCR ab function is challenging but might be pivotal in the comprehension of the aetiology of diseases. This, hopefully, will lead to the identification of novel therapeutic strategies. This article provides an overview about concepts and recent developments in research. Accordingly, GPCR abs could represent ideal candidates for precision medicine. Here, we introduce the term antibodiom to cover the network of abs with GPCR abs as prominent players.

17.
Internist (Berl) ; 60(12): 1251-1269, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31754753

RESUMO

Systemic sclerosis (SSc) is a rare fibrosing rheumatic multi-systemic disease involving many medical specialties. The mortality of SSc is determined by lung fibrosis, pulmonary arterial hypertension and cardiac involvement. With early and intensive treatment, the disease can be stabilized and symptoms relieved. This review summarizes insights into pathophysiology, disease classification, clinical manifestations and successful therapies, as well as recent studies on new immunosuppressant, biological and vasoactive therapies.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Fibrose Pulmonar/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Humanos , Hipertensão Pulmonar/etiologia , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/etiologia , Fibrose Pulmonar/etiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/terapia
18.
Arch Rheumatol ; 34(3): 253-261, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31598589

RESUMO

Objectives: This study aims to evaluate the prevalence of depressive symptoms among systemic sclerosis (SSc) patients using the Major Depression Inventory (MDI), identify possible risk factors, and analyze the current standard of care to raise awareness and improve clinical care for SSc patients. Patients and methods: The study included 94 SSc patients (12 males, 82 females; mean age 58.3±13.6 years; range, 28 to 83 years) who completed the MDI, Short Form 36 Health Survey, Scleroderma Health Assessment Questionnaire, Brief Fatigue Inventory and Physical Activity Questionnaire. Clinical parameters were assessed according to standardized procedures. Discharge letters were analyzed for evaluation of depressive symptoms. Results: The prevalence of depressive symptoms was 22.3%. It correlated with female sex (p=0.047), underweight (p=0.002), fatigue (p<0.001), decreased quality of life (p<0.001) and less physical activity (p=0.048). The latter three were confirmed as independent risk factors in a multivariable regression analysis. The analysis of the current standard of care revealed no assessment of depressive symptoms in the majority of patients (89.4%), including 19 with depressive symptoms according to the MDI score. Conclusion: This study confirms the high prevalence of depressive symptoms in SSc patients. There is an unmet need of regular assessment of mental health during SSc consultations. Fatigue, decreased quality of life and reduced physical activity were ascertained as independent risk factors, while special attention should also be paid to weight loss and underweight.

19.
Cells ; 8(10)2019 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614462

RESUMO

An acquired deficiency of interleukin-2 (IL-2) and related disturbances in regulatory T cell (Treg) homeostasis play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Low-dose IL-2 therapy was shown to restore Treg homeostasis in patients with active SLE and its clinical efficacy is currently evaluated in clinical trials. Lupus nephritis (LN), a challenging organ manifestation in SLE, is characterized by the infiltration of pathogenic CD4+ T cells into the inflamed kidney. However, the role of the Treg-IL-2 axis in the pathogenesis of LN and the mode of action of IL-2 therapy in the inflamed kidneys are still poorly understood. Using the (NZB × NZW) F1 mouse model of SLE we studied whether intrarenal Treg are affected by a shortage of IL-2 in comparison with lymphatic organs and whether and how intrarenal T cells and renal inflammation can be influenced by IL-2 therapy. We found that intrarenal Treg show phenotypic signs that are reminiscent of IL-2 deprivation in parallel to a progressive hyperactivity of intrarenal conventional CD4+ T cells (Tcon). Short-term IL-2 treatment of mice with active LN induced an expansion the intrarenal Treg population whereas long-term IL-2 treatment reduced the activity and proliferation of intrarenal Tcon, which was accompanied by a clinical and histological amelioration of LN. The association of these immune pathologies with IL-2 deficiency and their reversibility by IL-2 therapy provides important rationales for an IL-2-based immunotherapy of LN.


Assuntos
Interleucina-2/administração & dosagem , Interleucina-2/deficiência , Rim/imunologia , Nefrite Lúpica/tratamento farmacológico , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Injeções Subcutâneas , Interleucina-2/farmacologia , Rim/efeitos dos fármacos , Nefrite Lúpica/imunologia , Camundongos , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia
20.
Sci Rep ; 9(1): 14552, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601947

RESUMO

Although several risk factors exist for acute coronary syndrome (ACS) no biomarkers for survival or risk of re-infarction have been validated. Previously, reduced serum concentrations of anti-ß1AR Ab have been implicated in poorer ACS outcomes. This study further evaluates the prognostic implications of anti-ß1AR-Ab levels at the time of ACS onset. Serum anti-ß1AR Ab concentrations were measured in randomly selected patients from within the PLATO cohort. Stratification was performed according to ACS event: ST-elevation myocardial infarct (STEMI) vs. non-ST elevation myocardial infarct (NSTEMI). Antibody concentrations at ACS presentation were compared to 12-month all-cause and cardiovascular mortality, as well as 12-month re-infarction. Sub-analysis, stratifying for age and the correlation between antibody concentration and conventional cardiac risk-factors was subsequently performed. Serum anti-ß1AR Ab concentrations were measured in 400/799 (50%) STEMI patients and 399 NSTEMI patients. Increasing anti-ß1AR Ab concentrations were associated with STEMI (p = 0.001). Across all ACS patients, no associations between anti-ß1AR Ab concentration and either all-cause cardiovascular death or myocardial re-infarction (p = 0.14) were evident. However among STEMI patients ≤60 years with anti-ß1AR Ab concentration median (14/198 (7.1%) vs. 2/190 (1.1%)); p = 0.01). Similarly, the same sub-group demonstrated greater risk of cardiovascular death in year 1, including re-infarction and stroke (22/198 (11.1%) vs. 10/190 (5.3%); p = 0.017). ACS Patients ≤60 years, exhibiting lower concentrations of ß1AR Ab carry a greater risk for early re-infarction and cardiovascular death. Large, prospective studies quantitatively assessing the prognostic relevance of Anti-ß1AR Ab levels should be considered.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Anticorpos/sangue , Receptores Adrenérgicos beta 1/imunologia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Síndrome Coronariana Aguda/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Epitopos , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio , Prognóstico , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico
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