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1.
Clin Chem Lab Med ; 61(6): 1095-1104, 2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-36634098

RESUMO

OBJECTIVES: Autoantibodies and, specifically antinuclear antibodies (ANA), are the hallmark of systemic autoimmune diseases (AID). In the last decades, there has been great technical development to detect these autoantibodies along with an increased request for this test by clinicians, while the overall pre-test probability has decreased. In this study, we compare the diagnostic performance of three different methods for ANA screening (indirect immunofluorescence [IIF], addressable laser bead immunoassay [ALBIA], and fluorescence enzyme immunoassay [FEIA]). METHODS: Serum samples at baseline visit from 2,997 participants from the Camargo Cohort, a population with an overall low pre-test probability for systemic AID, were analyzed with the three methods. Participants have a minimum follow-up of 10 years and the development of autoimmune diseases was collected from clinical records. RESULTS: The highest frequency of positive ANA was observed by IIF assay. However, ALBIA showed high sensitivity for AID. Likewise, solid phase assays (SPA) presented higher specificity than IIF for AID. ANA prevalence with any method was significantly higher in females and overall increased with age. Triple positivity for ANA was significantly related to the presence of anti-dsDNA-SSA/Ro60, Ro52, SSB/La, RNP, Scl-70, and centromere-specificities. No association was found for anti-Sm - RNP68, or ribosomal P - specificities. Noteworthy, triple positivity for ANA screening was associated with diagnosis of systemic AID both at baseline visit and follow-up. CONCLUSIONS: ANA detection by IIF may be better when the pre-test probability is high, whereas SPA techniques are more useful in populations with an overall low pre-test probability for systemic AID.


Assuntos
Anticorpos Antinucleares , Doenças Autoimunes , Feminino , Humanos , Autoanticorpos , Doenças Autoimunes/diagnóstico , Técnica Indireta de Fluorescência para Anticorpo/métodos , Imunoensaio/métodos
2.
Rheumatology (Oxford) ; 60(11): 5329-5336, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33950249

RESUMO

OBJECTIVE: SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. METHODS: We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil ≥4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. RESULTS: From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. CONCLUSION: Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage.


Assuntos
Doenças do Sistema Digestório/etiologia , Lúpus Eritematoso Sistêmico/complicações , Sistema de Registros , Adulto , Comorbidade , Doenças do Sistema Digestório/epidemiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologia , Adulto Jovem
3.
Clin Exp Rheumatol ; 35 Suppl 105(3): 28-34, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28240585

RESUMO

OBJECTIVES: To assess fibromyalgia (FM) prevalence in a large cohort of primary Sjögren's syndrome patients (pSS) from a National Database. METHODS: Data included in the national retrospective register of pSS patients of the Spanish Society of Rheumatology (SJOGRENSER) were analysed. RESULTS: 437 pSS patients were included and a 14.6% of FM prevalence was found. FM-pSS patients significantly showed more constitutional, fatigue and arthralgia symptoms, splenomegaly, genital, skin and ear involvement and dyslipidaemia (p<0.05), as well as higher ESSPRI and SSDAI scores (p<0.01). Several symptomatic treatments were more frequently used in FM-pSS patients. No differences were observed in laboratory markers, imaging techniques or histologic inflammatory findings. Patients with FM showed statistically more fatigue than pSS without FM. In the multivariate logistic regression analysis several features were associated to pSS-FM patients. CONCLUSIONS: We show data on a reliable prevalence of FM in pSS patients and its multiple associated factors along with the presence of higher disease activity scores than patients who did not show FM. The presence of fatigue, arthralgia, constitutional symptoms and dyslipidaemia were more likely to coexist in pSS-FM patients.


Assuntos
Fibromialgia/epidemiologia , Sistema de Registros , Síndrome de Sjogren/epidemiologia , Adulto , Idoso , Artralgia/epidemiologia , Artralgia/etiologia , Dislipidemias/epidemiologia , Dislipidemias/etiologia , Fadiga/epidemiologia , Fadiga/etiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Estudos Retrospectivos , Reumatologia , Fatores de Risco , Síndrome de Sjogren/complicações , Síndrome de Sjogren/fisiopatologia , Dermatopatias/epidemiologia , Dermatopatias/etiologia , Sociedades Médicas , Espanha/epidemiologia , Esplenomegalia/epidemiologia , Esplenomegalia/etiologia
4.
Immunol Res ; 72(2): 260-270, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37924421

RESUMO

Autoantibodies are the hallmark of autoimmunity, and specifically, antinuclear antibodies (ANA) are one of the most relevant antibodies present in systemic autoimmune diseases (AID). In the present study, we evaluate the relationship between ANA and sociodemographic and biobehavioral factors in a population with a low pre-test probability for systemic AID. ANA were determined in serum samples at baseline visit from 2997 participants from the Camargo Cohort using indirect immunofluorescence assay, and two solid phase assays (SPA), addressable laser bead immunoassay, and fluorescence enzyme immunoassay. Sociodemographic and biobehavioral features of the subjects were obtained at baseline visit using a structured questionnaire. The prevalence of ANA positive results was significantly higher when indirect immunofluorescence assay was used as screening method in comparison with SPAs, being higher in females, older subjects, and those with higher C-reactive protein levels. Considering biobehavioral features, the prevalence was higher in those individuals with a sedentary lifestyle, and in ex- and non-alcohol users. Moreover, considering the relevance of the antibody load using ANA Screen, the prevalence of the antibody load also increased with age, especially in females. In conclusion, the prevalence of ANA varies depending on sociodemographic and biobehavioral features of the subjects, which could be relevant specifically in a population with a low pre-test probability for systemic AIDs.

5.
Semin Arthritis Rheum ; 61: 152232, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37348350

RESUMO

INTRODUCTION: Obstetric complications are more common in women with systemic lupus erythematosus (SLE) than in the general population. OBJECTIVE: To assess pregnancy outcomes in women with SLE from the RELESSER cohort after 12 years of follow-up. METHODS: A multicentre retrospective observational study was conducted. In addition to data from the RELESSER register, data were collected on obstetric/gynaecological variables and treatments received. The number of term pregnancies was compared between women with pregnancies before and after the diagnosis of SLE. Further, clinical and laboratory characteristics were compared between women with pregnancies before and after the diagnosis, on the one hand, and with and without complications during pregnancy, on the other. Bivariate and multivariate analyses were carried out to identify factors potentially associated with complications during pregnancy. RESULTS: A total of 809 women were included, with 1869 pregnancies, of which 1395 reached term. Women with pregnancies before the diagnosis of SLE had more pregnancies (2.37 vs 1.87) and a higher rate of term pregnancies (76.8% vs 69.8%, p < 0.001) compared to those with pregnancies after the diagnosis. Women with pregnancies before the diagnosis were diagnosed at an older age (43.4 vs 34.1 years) and had more comorbidities. No differences were observed between the groups with pregnancies before and after diagnosis in antibody profile, including anti-dsDNA, anti-Sm, anti-Ro, anti-La, lupus anticoagulant, anticardiolipin or anti-beta-2-glycoprotein. Overall, 114 out of the 809 women included in the study experienced complications during pregnancy, including miscarriage, preeclampsia/eclampsia, foetal death, and/or preterm birth. Women with complications had higher rates of antiphospholipid syndrome (40.5% vs 9.9%, p < 0.001) and higher rates of positivity for IgG anticardiolipin (33.9% vs 21.3%, p = 0.005), IgG anti-beta 2 glycoprotein (26.1% vs 14%, p = 0.007), and IgM anti-beta 2 glycoprotein (26.1% vs 16%, p = 0.032) antibodies, although no differences were found regarding lupus anticoagulant. Among the treatments received, only heparin was more commonly used by women with pregnancy complications. We did not find differences in corticosteroid or hydroxychloroquine use. CONCLUSIONS: The likelihood of term pregnancy is higher before the diagnosis of SLE. In our cohort, positivity for anticardiolipin IgG and anti-beta-2- glycoprotein IgG/IgM, but not lupus anticoagulant, was associated with a higher risk of poorer pregnancy outcomes.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Complicações na Gravidez , Nascimento Prematuro , Reumatologia , Gravidez , Humanos , Recém-Nascido , Feminino , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Síndrome Antifosfolipídica/complicações , Complicações na Gravidez/epidemiologia , Estudos Retrospectivos , beta 2-Glicoproteína I , Anticoagulantes , Imunoglobulina G , Imunoglobulina M
6.
Cell Immunol ; 273(2): 124-32, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22316526

RESUMO

PURPOSE: Aging is accompanied by a progressive increase in pro-inflammatory cytokine status. However, little is known about the development of age-dependent modifications in other circulating cytokines. The aim of this study was to investigate in vivo the influence of age on circulating cytokine production in healthy subjects (HC). METHODS: Circulating cytokines were measured by CBA and ELISA in 73 HC. Intracellular cytokine production was assessed in CD3+ and CD14+ cells by flow cytometry. Production of cytokines in cell culture supernatants was also studied after polyclonal stimulation. RESULTS: Subjects were divided into three different groups according to age: 28 young HC (<30 years, 26.2 ± 2.4), 24 middle age HC (30-60 years, 44.7 ± 8.4) and 21 elderly HC (>60 years, 70.6 ± 7.9). Age was positively correlated with the circulating levels of IL-12p70, IL-1ß, TNFα, IL-6, and IL-10. Age had a negative correlation with circulating levels of IL-17. Besides, age was positively correlated with spontaneous intracellular expression of proinflammatory cytokines in circulating monocytes. No correlation was found with other intracellular cytokine expression or with the production of cytokines in cell culture supernatants after in vitro stimulation. Gender had a marginal effect on the circulating cytokine profile. CONCLUSION: Aging has a significant impact on the production of circulating cytokines in healthy individuals. The circulating cytokine milieu may contribute to the development of age-restricted conditions.


Assuntos
Envelhecimento/imunologia , Citocinas/sangue , Monócitos/imunologia , Linfócitos T/imunologia , Equilíbrio Th1-Th2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Complexo CD3/imunologia , Células Cultivadas , Citocinas/biossíntese , Citocinas/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Receptores de Lipopolissacarídeos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Linfócitos T/citologia
7.
Clin Exp Rheumatol ; 29(5): 795-800, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22011399

RESUMO

OBJECTIVES: Coding variants in TLR4 gene have been reported to be associated with inflammatory diseases. The aim of this study was to determine whether two of these polymorphisms (Asp299Gly and Thr399Ile) of TLR4 contribute to the genetic background of polymyalgia rheumatica (PMR) and elderly-onset rheumatoid arthritis (EORA). Furthermore, we have attempted to correlate the functional consequences of these polymorphisms. METHODS: 164 patients with PMR, 93 with EORA and 126 unrelated age-matched controls were genotyped. The TLR4 genotypes were determined using allele-specific primers and restriction fragment length polymorphism analysis. Association of genotypes and alleles with disease susceptibility and disease phenotypes were studied. TLR4 expression was assessed on PBMCs by flow cytometry and TLR4 function was assessed by stimulating PBMCs in vitro with LPS. RESULTS: No significant difference in allele frequency or genotype between patients with elderly-onset inflammatory conditions and controls was observed. The Thr399Ile CC genotype was associated with a higher cumulative dose of corticosteroids in patients with PMR (p=0.031). We found no association with TLR4 expression on B cells, T cells or monocytes or a distinct phenotype of TLR4 response with the Asp299Gly or Thr399Ile genotypes. CONCLUSIONS: These results do not support the association of these TLR4 variants with two age-related inflammatory conditions. The value of determining Thr399Ile genotypes for disease prognosis in PMR should be confirmed in different populations.


Assuntos
Artrite Reumatoide/genética , Polimorfismo Genético/genética , Polimialgia Reumática/genética , Receptor 4 Toll-Like/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/imunologia , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimialgia Reumática/imunologia
8.
Reumatol Clin (Engl Ed) ; 17(2): 61-66, 2021 Feb.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31784396

RESUMO

OBJECTIVE: Pregnancy and puerperium are considered a risk situation in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Therefore, specialized assessment is essential both preconception and during pregnancy and the puerperium. Likewise, it is very important that different specialists in autoimmune diseases and high-risk pregnancies participate in the follow-up of these patients in a coordinated manner. The Spanish Society of Gynaecology and Obstetrics, the Spanish Society of Internal Medicine, and the Spanish Society of Rheumatology have set up a working group for the preparation of three consensus documents. METHODS: The stages of the work were: distribution of work in three groups corresponding to the three periods related to pregnancy (preconception, during pregnancy and childbirth and puerperium), identification of key areas, exhaustive review of the literature and formulation of recommendations. RESULTS: This first document includes the 48 recommendations that address aspects related to infertility, the need for and treatments for gonadal preservation and preconception assessment. CONCLUSIONS: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with SLE/APS during pregnancy.

9.
Reumatol Clin (Engl Ed) ; 16(2 Pt 1): 71-86, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30713012

RESUMO

OBJECTIVE: The difficulty in diagnosis and the spectrum of clinical manifestations that can determine the choice of treatment for primary antiphospholipid syndrome (APS) has fostered the development of recommendations by the Spanish Society of Rheumatology (SER), based on the best possible evidence. These recommendations can serve as a reference for rheumatologists and other specialists involved in the management of APS. METHODS: A panel of four rheumatologists, a gynaecologist and a haematologist with expertise in APS was created, previously selected by the SER through an open call or based on professional merits. The stages of the work were: identification of the key areas for drafting the document, analysis and synthesis of the scientific evidence (using the Scottish Intercollegiate Guidelines Network [SIGN] levels of evidence) and formulation of recommendations based on this evidence and formal assessment or reasoned judgement techniques (consensus techniques). RESULTS: 46 recommendations were drawn up, addressing five main areas: diagnosis and evaluation, measurement of primary thromboprophylaxis, treatment for APS or secondary thromboprophylaxis, treatment for obstetric APS and special situations. These recommendations also include the role of novel oral anticoagulants, the problem of recurrences or the key risk factors identified in these subjects. This document reflects the first 21, referring to the areas of: diagnosis, evaluation and treatment of primary APS. The document provides a table of recommendations and treatment algorithms. CONCLUSIONS: An update of the SER recommendations on APS is presented. This document corresponds to partI, related to diagnosis, evaluation and treatment. These recommendations are considered tools for decision-making for clinicians, taking into consideration both the decision of the physician experienced in APS and the patient. A partII has also been prepared, which addresses aspects related to obstetric SAF and special situations.


Assuntos
Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Síndrome Antifosfolipídica/complicações , Humanos , Sociedades Médicas , Espanha
10.
Hum Immunol ; 70(1): 49-54, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19026700

RESUMO

The objective of this study was to investigate whether there is an association between IL1RN polymorphism and disease susceptibility for three age-related inflammatory conditions: polymyalgia rheumatica (PMR), giant cell arteritis (GCA), and elderly-onset rheumatoid arthritis (EORA). A tandem-repeat polymorphism within IL1RN intron 2 was analyzed in 139 PMR, 69 GCA, and 156 RA patients (75 with EORA) as well as in 437 healthy subjects, together with the in vitro production of IL-1beta. Our results showed that the IL1RN*2/2 genotype was more frequent in PMR patients compared with controls (p = 0.032, odds ratio = 1.785, 95% confidence interval = 1.047-3.044) and GCA patients (p = 0.008, odds ratio = 4.661, 95% confidence interval = 1.352-16.065). We found no difference in the distribution of genotypes between PMR and EORA or between EORA and controls. However, the frequency of the IL-1RN*2/2 genotype had a tendency to be higher in patients with EORA compared with young onset RA. The presence of IL1RN*1 or IL1RN*2 allele was not associated with severity of the disease in PMR and GCA patients and did not influence the production of IL-1beta. In conclusion, the IL1RN*2 polymorphism in a homozygous state was associated with an increased susceptibility to PMR and may give some clues for a differential therapy with GCA.


Assuntos
Envelhecimento/fisiologia , Artrite Reumatoide/genética , Arterite de Células Gigantes/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Polimorfismo Genético , Polimialgia Reumática/genética , Idoso , Doença Crônica , Feminino , Predisposição Genética para Doença , Genótipo , Homozigoto , Humanos , Interleucina-1beta/metabolismo , Masculino , Pessoa de Meia-Idade
11.
Gastroenterol Hepatol ; 32(10): 681-6, 2009 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-19783075

RESUMO

We present the case of a 23-year-old man with fever of unknown origin, who developed acute liver failure 2 months after symptom onset, requiring an urgent liver transplantation. The diagnosis of adult-onset Still's disease was established after the reappearance of symptoms after transplantation, and high doses of corticosteroids were used to control disease activity. Subsequently, given the impossibility of tapering the steroid dose, interleukin-1 receptor blocking treatment was started with satisfactory outcome. We also review the published literature.


Assuntos
Falência Hepática/etiologia , Transplante de Fígado , Doença de Still de Início Tardio/cirurgia , Corticosteroides/uso terapêutico , Emergências , Febre de Causa Desconhecida/etiologia , Humanos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Falência Hepática/cirurgia , Masculino , Doença de Still de Início Tardio/complicações , Doença de Still de Início Tardio/tratamento farmacológico , Adulto Jovem
12.
Cytokine ; 44(2): 207-20, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18986814

RESUMO

OBJECTIVE: To summarize the contribution of cytokines to pathogenesis, clinical manifestations and prognosis of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). METHODS: MEDLINE database search for studies published between 1980 and April 2008. RESULTS: PMR and GCA are characterized by a hyperproduction of IL-6. The role of other circulating cytokines in their pathogenesis remains unclear. Cytokine mRNA in the arterial wall of GCA can distinguish different clinical subgroups of patients. The profile of T cell-derived cytokines in GCA suggests that it is a Th1-driven disease. The scarce number of studies makes difficult to evaluate the exact contribution of cytokine polymorphisms to their pathogenesis. Small studies have suggested the utility of TNF antagonists in patients with refractory PMR and GCA. However, these data have not been confirmed in controlled studies in patients with recent onset disease. CONCLUSION: Further studies are needed to evaluate the role of circulating cytokines in PMR and GCA. The study of tissue cytokines has provided important insights into the mechanisms implicated in the local inflammatory response that occurs in GCA. The important advance in the knowledge of the role of cytokines in PMR and GCA will have clear implications for treatment.


Assuntos
Citocinas/imunologia , Arterite de Células Gigantes , Polimialgia Reumática , Animais , Citocinas/sangue , Arterite de Células Gigantes/imunologia , Arterite de Células Gigantes/fisiopatologia , Arterite de Células Gigantes/terapia , Humanos , Interleucina-6/imunologia , MEDLINE , Polimialgia Reumática/imunologia , Polimialgia Reumática/fisiopatologia , Polimialgia Reumática/terapia
13.
Clin Rheumatol ; 27(1): 107-10, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17982708

RESUMO

Schnitzler's syndrome is a rare combination of chronic urticaria, fever of unknown origin, disabling bone pain, and monoclonal gammopathy. We report a case with an unusual radiological manifestation as a solitary sclerotic lesion of the right iliac bone. Its main features on conventional radiography, computed tomography, and magnetic resonance imaging are described, and the main radiological differential diagnoses are discussed to help with the characterization of this syndrome, which requires a combination of clinical, laboratory, and radiological data. On the other hand, although our patient had an excellent clinical response to anakinra, the sclerotic lesion remained unchanged on follow-up X-ray examinations.


Assuntos
Diagnóstico por Imagem/métodos , Síndrome de Schnitzler/diagnóstico por imagem , Síndrome de Schnitzler/patologia , Adulto , Antirreumáticos/uso terapêutico , Quimioterapia Combinada , Humanos , Ílio/diagnóstico por imagem , Ílio/patologia , Imunossupressores/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Metotrexato/uso terapêutico , Dor/tratamento farmacológico , Dor/patologia , Síndrome de Schnitzler/tratamento farmacológico , Esclerose/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Urticária/tratamento farmacológico , Urticária/patologia
14.
Med Clin (Barc) ; 148(9): 394-400, 2017 May 10.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28153433

RESUMO

INTRODUCTION: The antiphospholipid syndrome (APS) is an acquired immune disorder defined by the presence of thrombosis (arterial and/or venous) and/or pregnancy morbidity along with the presence of positive antiphospholipid antibodies (aPL). There is a clear relationship between aPL and some events not included in the clinical criteria, including haematologic. OBJECTIVES: a) to study the probability of developing clinical APS in patients with positive aPL and thrombopenia; b) to identify potential risk factors for thrombosis, and c) to study the association between thrombocytopenia and aPL. METHODS: A retrospective study of 138 patients with positive aPL without fulfilling clinical criteria for APS. Thrombocytopenia was defined as a platelet count≤100,000/µl. Patients with other causes of thrombocytopenia were excluded. RESULTS: Seventeen of the 138 (12%) patients in the study had thrombocytopenia. The mean platelet count was 60,000/µl. The risk of developing thrombocytopenia was higher in smokers (OR 2.8; P=.044), in those with lupus anticoagulant (OR 13.5; P<.001) and those with higher burden of aPL (OR 50.8; P<.001). After a mean follow-up of 146±60.3 months, 5 patients with thrombocytopenia (29.4%) developed thrombosis. CONCLUSIONS: In our series, the incidence of thrombocytopenia is 12%. aPL-positive patients who develop thrombocytopenia have a potential risk of developing thrombosis. Tobacco could be a risk factor for thrombocytopenia. Autoantibodies load is a risk factor for the development of thrombocytopenia.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/diagnóstico , Trombocitopenia/complicações , Trombose/etiologia , Adolescente , Adulto , Idoso , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombocitopenia/diagnóstico , Trombose/diagnóstico , Adulto Jovem
15.
PLoS One ; 12(10): e0185889, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28982122

RESUMO

Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity.


Assuntos
Doenças Autoimunes/complicações , Doenças Cardiovasculares/etiologia , Predisposição Genética para Doença , Variação Genética , Doenças Cardiovasculares/genética , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
16.
Reumatol Clin ; 11(5): 279-94, 2015.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26051464

RESUMO

OBJECTIVE: To establish recommendations for the management of patients with rheumatoid arthritis (RA) to serve as a reference for all health professionals involved in the care of these patients, and focusing on the role of available synthetic and biologic disease-modifying antirheumatic drugs (DMARDs). METHODS: Consensual recommendations were agreed on by a panel of 14 experts selected by the Spanish Society of Rheumatology (SER). The available scientific evidence was collected by updating three systematic reviews (SR) used for the EULAR 2013 recommendations. A new SR was added to answer an additional question. The literature review of the scientific evidence was made by the SER reviewer's group. The level of evidence and the degree of recommendation was classified according to the Oxford Centre for Evidence-Based Medicine system. A Delphi panel was used to evaluate the level of agreement between panellists (strength of recommendation). RESULTS: Thirteen recommendations for the management of adult RA were emitted. The therapeutic objective should be to treat patients in the early phases of the disease with the aim of achieving clinical remission, with methotrexate playing a central role in the therapeutic strategy of RA as the reference synthetic DMARD. Indications for biologic DMARDs were updated and the concept of the optimization of biologicals was introduced. CONCLUSIONS: We present the fifth update of the SER recommendations for the management of RA with synthetic and biologic DMARDs.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Terapia Biológica/métodos , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Humanos , Reumatologia , Sociedades Médicas , Espanha
17.
Autoimmun Rev ; 13(8): 788-94, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24667078

RESUMO

OBJECTIVE: To evaluate the effect of antiplatelet/anticoagulant therapy on the occurrence of severe ischemic complications in GCA patients at diagnosis and while on treatment with corticosteroids (CS), and the risk of bleeding in these patients. METHODS: A comprehensive search of PubMed and the Cochrane Central Register of Controlled Trials databases was completed and supplemented by hand searching of the references of all selected articles published from 1992 through December 2012. The cumulative meta-analysis included 6 retrospective studies that provided a total of 914 GCA patients. The effect of established antiplatelet/anticoagulant therapy on the occurrence of severe ischemic complications in patients with GCA at diagnosis and on the development of new severe ischemic complications in patients with GCA after diagnosis and while on treatment with CS were evaluated; as well as the risk of bleeding in patients with GCA on concomitant treatment with CS and antiplatelet/anticoagulant therapy. RESULTS: Antiplatelet/anticoagulant therapy before the diagnosis of GCA was not associated with a protection to develop severe ischemic complications (OR: 0.661; 95% CI [0.287-1.520]; p=0.33). However, such a therapy may prevent from severe ischemic complications after the diagnosis of GCA (OR: 0.318; [0.101-0.996]; p=0.049) without increasing the risk of bleeding in patients with GCA on concomitant treatment with CS (OR: 0.658; [0.089-4.856]; p=0.682). CONCLUSIONS: Antiplatelet/anticoagulant therapy prior to the diagnosis of GCA was not associated with reduction in severe ischemic complications. However, antiplatelet/anticoagulant therapy demonstrated a marginal benefit when used together with CS therapy in patients with established GCA without associated bleeding risk.


Assuntos
Anticoagulantes/uso terapêutico , Arterite de Células Gigantes/complicações , Hemorragia/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Corticosteroides/uso terapêutico , Anticoagulantes/efeitos adversos , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/epidemiologia , Hemorragia/induzido quimicamente , Hemorragia/complicações , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos
18.
Clin Rev Allergy Immunol ; 47(1): 56-64, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24395029

RESUMO

Polymorphisms of cytokine genes have been investigated as susceptibility markers of giant cell arteritis (GCA). Here, we have reviewed the evidence to date and especially addressed the functional consequences of IL10 (-592C/A and -1082A/G) gene polymorphisms and their association with susceptibility to and disease phenotype in GCA. A total number of 71 patients with GCA and 124 age-matched controls were genotyped using allele-specific primers and restriction fragment length polymorphism analysis. As previous studies in GCA showed inconsistent results, a meta-analysis of the existing studies was also conducted by using both fixed and random-effects models. The levels of circulating IL10 and the production of IL10 by peripheral blood mononuclear cells after in vitro stimulation were studied by Cytometric Bead Array. Data showed no significant differences in genotype or allele frequency distribution between patients and controls. The clinical characteristics and prognosis of these patients were also unrelated to the presence of these polymorphisms. However, the meta-analysis found a significant association of IL10 -592C/A polymorphism with susceptibility to GCA (odds ratio 2.205 (95% confidence interval 1.074-4.524); p = 0.031). In both patients and age-matched controls, no differences in circulating IL10 levels or IL10 production were observed depending on the genotypes of the IL10 gene. In conclusion, although our cohort results do not support the impact of IL10 variants in susceptibility or clinical phenotype of GCA patients, the meta-analysis revealed a significant association of -592C/A polymorphism with susceptibility to GCA. In this population, no functional association was found between IL10 gene variants and IL10 production.


Assuntos
Predisposição Genética para Doença , Arterite de Células Gigantes/genética , Interleucina-10/genética , Leucócitos Mononucleares/imunologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Regiões Promotoras Genéticas/genética
19.
J Leukoc Biol ; 94(5): 1071-8, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23904438

RESUMO

This study was conducted to evaluate phagocyte function in patients with age-related chronic inflammatory conditions. It included 95 patients with PMR, 17 with GCA, 40 with EORA, and 25 age-matched HCs. Serum IL-8 was determined with a bead array. The chemotactic capacity, phagocytic ability, and oxidative burst activity of circulating leukocytes were determined with flow cytometry kits. Patients with active chronic inflammatory diseases showed a significant increase in circulating levels of IL-8 that remained elevated in patients with PMR or EORA, despite treatment. No correlation was found between circulating IL-8 and the migratory capacity of neutrophils. Neutrophils from patients with active EORA without stimulus and after fMLP stimuli showed a higher capacity to migrate than those of the HCs (P=0.033). The phagocytic activity of granulocytes in the patients with GCA was significantly higher than in the HCs and the patients with PMR or EORA (P<0.05). The percentage and MFI of phagocytes that produce ROIs when stimulated with Escherichia coli was significantly reduced in neutrophils and monocytes from the patients with age-restricted inflammatory conditions. We concluded that the effector functions of phagocytes, determined to be chemotaxis, phagocytosis, and oxidative burst, are deregulated in age-restricted inflammatory disorders and may have a pathogenic role.


Assuntos
Artrite Reumatoide/imunologia , Arterite de Células Gigantes/imunologia , Fagócitos/imunologia , Polimialgia Reumática/imunologia , Reação de Fase Aguda , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Quimiotaxia de Leucócito , Doença Crônica , Feminino , Humanos , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Explosão Respiratória
20.
J Leukoc Biol ; 91(5): 829-38, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22345707

RESUMO

This study investigated in vivo the influence of age and vitamin D status on innate immune function in HC. Serum 25OHD was measured in 71 HC. TLR expression on various subpopulations of PBMCs, as well as TLR function by stimulating PBMCs with specific ligands, was assessed by flow cytometry. Circulating cathelicidin levels were determined by ELISA. Serum 25OHD levels decreased with age, and there was a significant inverse correlation between 25OHD levels and age. There was a negative correlation between serum 25OHD levels and MFI expression of TLR7 on B cells, T cells, and monocytes. TLR7 function, addressed by in vitro stimulation with a specific agonist, was significantly correlated with serum 25OHD levels, and this was especially a result of the results in HC older than 60 years. MFI expression of TLR5 on T cells and TLR2 on monocytes was also negatively correlated with serum 25OHD levels. TLR1 (monocytes) and TLR2 (monocytes) expression was positively correlated with age. Furthermore, TLR4 and TLR8 function was negatively correlated with age. Circulating cathelicidin levels decreased with age and were positively correlated with 25OHD levels. Aging is accompanied by changes in expression and function of several TLRs. Serum 25OHD levels decrease with age and are also associated with a change in expression and defective function of certain TLRs, especially those involved in viral response.


Assuntos
Imunidade Inata/imunologia , Monócitos/imunologia , Monócitos/patologia , Vitamina D/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Ensaio de Imunoadsorção Enzimática , Humanos , Pessoa de Meia-Idade , Monócitos/metabolismo , Receptores Toll-Like/sangue , Adulto Jovem
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