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3.
J Rheumatol ; 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31308212

RESUMO

We read the editorial by Sandhu, et al 1 about antimalarial-induced cardiomyopathy in systemic lupus erythematosus2, and we want to point out some inaccuracies in the brief review of the history of antimalarials that they presented.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31302689

RESUMO

OBJECTIVE: The aim was to evaluate whether T cell subsets and the lipid profile could be linked to the cardioprotective effect of IgM anti-phosphorylcholine (PC) antibodies in SLE. METHODS: Anti-PC antibodies were quantified by ELISA in 197 patients and 99 controls and analysed in relationship to clinical features, treatments and serum lipids. Carotid atheromatosis was evaluated by ultrasonography; Th1, Th17, Treg and CD4+CD28null cells by flow cytometry; and cytokine serum levels by immunoassays, in a subgroup of 120 SLE patients and 33 controls. RESULTS: IgM anti-PC serum levels were reduced in SLE patients compared with controls (P < 0.001) and were associated with age (ß= -0.252; P = 0.002), high-density lipoprotein (HDL; ß = 0.271; P = 0.001), low-density lipoprotein (LDL; ß= -0.192; P = 0.017) and glucocorticoid treatment (ß= -0.201; P = 0.012), whereas the IgG-to-IgM anti-PC ratio was increased (P = 0.007) and associated with age (ß = 0.194; P = 0.028) and SLEDAI (ß = 0.250; P = 0.005). Also, patients with clinical or subclinical cardiovascular disease exhibited reduced IgM anti-PC levels compared with their cardiovascular disease-free counterparts, regardless of glucocorticoid usage (P = 0.001). CD4+CD28null and Th17 cells were increased in SLE patients compared with controls (P < 0.01) and correlated inversely with IgM anti-PC levels. These associations were observed in patients displaying high triglyceride or low HDL levels, even after adjusting for clinical parameters and treatments (CD4+CD28null: ß = -0.455, P = 0.001; Th17: ß= -0.280, P = 0.035), but not in those with a normal lipid profile. High triglyceride and low HDL profiles were related to low IgM anti-PC and Treg levels, respectively, whereas both lipid profiles were associated with inflammatory markers and cytokines. CONCLUSION: The present study provides evidence for an association of IgM anti-PC antibodies with pro-atherogenic T cell subsets in SLE, with a high triglyceride/low HDL lipid profile playing a facilitating major role.

7.
Reumatol Clin ; 2019 May 08.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31078455

RESUMO

OBJECTIVE: To describe the frequency and profile of patients with neuro-Behçet's disease (NBD) at the Central University Hospital of Asturias between 1981 and June 2018. PATIENTS AND METHODS: Retrospective study including epidemiological, clinical, neuroimaging, cerebrospinal fluid (CSF) study, histopathology, treatment and evolution characteristics. Clinical characteristics are differentiated between patients with Behçet without neurological affectation and NBD. RESULTS: We found 10 cases of NBD (25.6%). The mean age was 29.7years, and it was more frequent in males. Sixty percent had parenchymal involvement. The non-parenchymal involvement included a case with cerebral venous thrombosis and two cases with isolated aseptic meningitis. Findings of vasculitis were found on cerebral magnetic resonance imaging, and alteration in the biochemistry of the CSF. One patient presented a striking motor disability. Ocular involvement was greater in the group of patients without neurological involvement (P=0.009). CONCLUSIONS: NBD is a relatively frequent presentation, especially in males and in the parenchymal form. We did not find a systemic clinical marker of neurological involvement.

10.
Reumatol Clin ; 2018 Oct 05.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30297197

RESUMO

IgG4-related disease is characterized by a lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. It can present as parotid gland enlargement, tubulointerstitial nephritis, retroperitoneal fibrosis or pancreatitis, although nearly any organ can be affected. We report the case of a 37-year-old woman who presented with severe dysphonia and recurrent painful aphthous ulcers, with histopathological findings at the level of the larynx that revealed a lymphoplasmacytic infiltrate and IgG4 positivity. In addition, extensive studies were performed to rule out other diseases. Thus the diagnosis was IgG4-related laryngitis, an exceptional finding in the literature.

11.
Mayo Clin Proc Innov Qual Outcomes ; 2(3): 267-276, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30225460

RESUMO

Objective: To characterize the etiologies and clinical features at diagnosis of patients with hemophagocytic lymphohistiocytosis (HLH) and correlate these baseline features with survival using an etiopathogenically guided multivariable model. Patients and Methods: The Spanish Group of Autoimmune Diseases HLH Study Group, formed in 2013, is aimed at collecting adult patients with HLH diagnosed in internal medicine departments between January 3, 2013, and October 28, 2017. Results: The cohort consisted of 151 patients (91 men; mean age, 51.4 years). After a mean follow-up of 17 months (range, 1-142 months), 80 patients died. Time-to-event analyses for death identified a worse survival curve for patients with neoplasia (P<.001), mixed microbiological infections (P=.02), and more than 1 infection (P=.01) and glucocorticoid monotherapy (P=.02). According to univariate analyses, platelets of less than 100,000/mm3 (hazard ratio [HR], 3.39; 95% CI, 1.37-8.40), leukopenia (HR, 1.81; 95% CI, 1.01-3.23), severe hyponatremia (HR, 1.61; 95% CI, 1.02-2.54), disseminated intravascular coagulation (HR, 1.87; 95% CI, 1.05-3.34), bacterial infection (HR, 1.99; 95% CI, 1.09-3.63), mixed microbiological infections (HR, 3.42; 95% CI, 1.38-8.46), and 2 or more infectious triggers (HR, 2.95; 95% CI, 1.43-6.08) were significantly associated with death. In contrast, peripheral adenopathies (HR, 0.63; 95% CI, 0.40-0.98) and the immunosuppressive drug/intravenous immunoglobulin/biological therapies (HR, 0.44; 95% CI, 0.20-0.96) were protective against all-cause mortality. Multivariable Cox proportional hazards regression analysis identified 2 or more infectious triggers (HR, 3.14; 95% CI, 1.28-7.68) as the only variable independently associated with death. Conclusion: The mortality rate of adult patients diagnosed with HLH exceeds 50%. Infection with more than 1 microbiological agent was the only independent variable associated with mortality irrespective of the underlying disease, epidemiological profile, clinical presentation, and therapeutic management.

14.
Reumatol Clin ; 2018 May 15.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29776888

RESUMO

IgA vasculitis is a small-vessel vasculitis mediated by immune complexes. In clinical terms, it is characterized by palpable purpura in the lower limbs, joint involvement in the form of arthralgia or arthritis, and gastrointestinal and renal involvement (this will mark a poorer prognosis in adults). Infectious processes, mainly in the upper respiratory tract, are frequently found to be triggers. On the other hand, human immunodeficiency virus (HIV) causes immune dysfunction, which triggers hypergammaglobulinemia and can trigger autoimmune disorders. At times, this can affect the vascular endothelium, giving rise to vasculitic manifestations, although there are few reports in the literature of its role in the presentation of HIV.

17.
Front Immunol ; 9: 3085, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30666255

RESUMO

Introduction: Overactivation of the type I interferon (IFN) signature has been observed in several systemic autoimmune conditions, such as Systemic Lupus Erythematosus (SLE) or Rheumatoid Arthritis (RA). Impaired control of Interferon-Responding Genes (IRGs) expression by their regulatory mechanisms, including Interferon Regulatory Factors (IRFs), may underlie these findings and it may explain the heterogeneity observed among these conditions. In the present study we aimed to evaluate the associations between IRF4 gene expression and those of IRGs in SLE and RA patients to gain insight about its links with the IFN signature as well as to explore the potential clinical relevance of these associations. Methods: The gene expression of IRF4 and IRGs (IFI44, IFI44L, IFI6, and MX1) in peripheral blood was analyzed in 75 SLE patients, 98 RA patients, and 28 healthy controls. A group of 13 biological-naïve RA patients was prospectively followed upon TNFα-blockade. The associations among IRF4 and IRGs were evaluated by principal component analyses (PCA), correlations and network analyses. Publicly available datasets were used for replication. Results: A broad activation of IRGs was observed in autoimmune patients, although certain heterogeneity can be distinguished, whereas IRF4 was only upregulated in RA. The differential expression of IRF4 in RA was then confirmed in publicly available gene expression datasets. PCA revealed different associations among IRF4 and IRGs in each condition, which was later confirmed by correlation and network analyses. Cluster analysis identified 3 gene expression signatures on the basis of IRF4 and IRGs expression which were differentially used by SLE and RA patients. Cluster III was associated with markers of disease severity in SLE patients. Cluster II, hallmarked by IRF4 upregulation, was linked to clinical stage and mild disease course in RA. TNFα-blockade led to changes in the association between IRF4 and IRGs, whereas increasing IRF4 expression was associated with a good clinical outcome in RA. Conclusions: The differential expression of IRF4 and IRGs observed in SLE and RA can delineate gene expression signatures associated with clinical features and treatment outcomes. These results support a clinically-relevant phenomenon of shaping of the IFN signature by IRF4 in autoimmune patients.


Assuntos
Antígenos/genética , Artrite Reumatoide/genética , Proteínas do Citoesqueleto/genética , Fatores Reguladores de Interferon/genética , Lúpus Eritematoso Sistêmico/genética , Proteínas Mitocondriais/genética , Proteínas de Resistência a Myxovirus/genética , Transcriptoma , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos/sangue , Artrite Reumatoide/sangue , Distribuição de Qui-Quadrado , Análise por Conglomerados , Proteínas do Citoesqueleto/sangue , Feminino , Seguimentos , Humanos , Fatores Reguladores de Interferon/sangue , Interferon Tipo I/genética , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/sangue , Proteínas de Resistência a Myxovirus/sangue , Estudos Prospectivos , Estatísticas não Paramétricas , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Proteínas Supressoras de Tumor/sangue , Adulto Jovem
19.
Thromb Haemost ; 117(11): 2194-2206, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29044294

RESUMO

The present study aimed to evaluate the possible role of immunoglobulin G (IgG) antibodies against high-density lipoproteins (HDL) and paraoxonase 1 (PON1) as possible biomarkers of cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). To this end, levels of these autoantibodies, PON1 activity and total antioxidant capacity were quantified in serum samples from 198 SLE patients, 100 healthy controls (HC) and 42 non-autoimmune individuals with traditional cardiovascular risk factors. PON1 rs662 polymorphism was analysed in a subgroup of patients and controls. Subclinical CVD were determined by Doppler ultrasound in 118 SLE patients and 30 HC, analysing carotid intima-media thickness (IMT) and blood flow parameters in internal carotid, middle cerebral and basilar arteries. Serum levels of both anti-HDL and anti-PON1 antibodies were increased in SLE patients compared with HC (p < 0.001); however, only anti-PON1 antibodies, in addition to disease activity, were significant predictors of the impaired PON1 function in SLE (ß = -0.143, p = 0.045). Conversely, anti-HDL antibodies were associated with higher risk of CVD (odds ratio: 3.69; p = 0.012) and lower HDL levels at disease onset (ρ = -0.324, p = 0.044). Finally, anti-PON1 antibodies were associated with carotid IMT in SLE (ß = 0.201, p = 0.008) and inversely related to cranial arteries blood flow velocities in patients with clinical and subclinical CVD (all p < 0.001). In sum, these findings allowed us to propose serum levels of anti-PON1 and anti-HDL antibodies as potential early biomarkers of endothelial damage and premature atherosclerosis in SLE, thus constituting useful therapeutic targets for the prevention of future CVD in these patients.


Assuntos
Arildialquilfosfatase/imunologia , Autoanticorpos/sangue , Doenças das Artérias Carótidas/sangue , Imunoglobulina G/sangue , Lipoproteínas HDL/imunologia , Lúpus Eritematoso Sistêmico/sangue , Adulto , Antioxidantes/análise , Arildialquilfosfatase/genética , Biomarcadores/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/imunologia , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Prevalência , Fatores de Risco , Espanha/epidemiologia , Ultrassonografia Doppler
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