Los anticuerpos anti-Ro52/TRIM21 están asociados a circuitos inflamatorios aberrantes en pacientes con enfermedades reumáticas autoinmunes sistémicas / Anti-Ro52/TRIM21 antibodies are associated with aberrant inflammatory circuits in patients with systemic autoimmune rheumatic diseases

Resumen Introducción: Los anticuerpos anti-Ro52/TRIM21 son marcadores de varias enfermedades reumáticas autoinmunes sistémicas (ERAS). Objetivo: Evaluar si los anticuerpos anti-Ro52/TRIM21 están relacionados con anomalías en los circuitos inflamatorios. Métodos: Estudio transversal de pacientes consecutivos y ambulatorios con ERAS. Los anticuerpos anti-Ro52/TRIM21 y la proteína amiloide sérica se midieron mediante ELISA; los paneles para 18 citocinas y nueve quimiocinas se analizaron en una plataforma de lectura Luminex; la proteína C reactiva (hs-CRP) y el complemento se midieron mediante nefelometría. Resultados: Se incluyeron 167 pacientes, 143 con lupus eritematoso sistémico (LES), 16 con síndrome de Sjögren primario y ocho con esclerosis sistémica; 41 fueron positivos para anticuerpos anti-Ro52/TRIM21 (24 %). Los pacientes con anticuerpos anti-Ro52/TRIM21 tuvieron niveles séricos más altos de IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP y quimiocinas CCL4, CXCL8, CXCL10 y CXCL12; y más bajos de complemento C4. Los títulos de anticuerpos anti-Ro52/TRIM21 correlacionaron positivamente con IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10 y hs-CRP; y negativamente con complemento C3 y C4. Al incluir solo LES, no se identificó asociación entre los anticuerpos anti-Ro52/TRIM21 y la actividad de la enfermedad o la afectación específica de órganos. Conclusiones: Los anticuerpos anti-Ro52/TRIM21 se asocian a circuitos aberrantes de citocinas y niveles elevados de moléculas angiogénicas y quimioatrayentes de neutrófilos y monocitos, lo que sugiere un papel activo de esos anticuerpos en las ERAS.

Abstract Introduction: Anti-Ro52/TRIM21 antibodies are markers for several systemic autoimmune rheumatic diseases (SARD). Objective: To assess whether anti-Ro52/TRIM21 antibodies are related to abnormalities in inflammatory circuits. Methods: Cross-sectional study of consecutive outpatients with SARD. Anti-Ro52/TRIM21 antibodies and serum amyloid A protein were measured by ELISA; panels for 18 cytokines and nine chemokines were analyzed on a Luminex reading platform, while high-sensitivity C-reactive protein (hs-CRP) and complement were measured by nephelometry. Results: Among 167 included patients, 143 had systemic lupus erythematosus (SLE), 16 had primary Sjögren's syndrome and eight had systemic sclerosis; 41 (24%) were positive for anti-Ro52/TRIM21 antibodies. Patients with anti-Ro52/TRIM21 antibodies had higher serum levels of IL-2, IL-4, IL-6, GM-CSF, IL-21, IL-22, hs-CRP and chemokines CCL4, CXCL8, CXCL10 and CXCL12, but lower levels of complement C4. Anti-Ro52/TRIM21 antibody titers were positively correlated with IL-2, IL-4, IL-6, IL-10, IL-21, IL-22, CXCL10, and hs-CRP, and negatively with complement C3 and C4. When only SLE patients were included, no association was identified between anti-Ro52/TRIM21 antibodies and disease activity or organ-specific involvement. Conclusions: Anti-Ro52/TRIM21 antibodies are associated with aberrant cytokine circuits and elevated levels of angiogenic molecules and neutrophil and monocyte chemoattractants, which suggests an active role for these antibodies in SARD.

Cardiovascular risk in the postnatal life of children born to women with systemic lupus erythematous / Riesgo cardiovascular en la vida posnatal de hijos de mujeres con lupus eritematoso sistémico

Abstract Systemic lupus erythematous (SLE) is an autoimmune disease with clinical manifestations in multiple organs, primarily striking women of reproductive age. Women with SLE can became pregnant such as any other healthy woman and carrier their pregnancy to term due to the improvement of health systems, but their specific inflammatory conditions could affect the microenvironment in which the fetus grows, and influence the development of placenta and the fetal heart. Until now, there is very little evidence of any increased risk of postnatal cardiovascular disease (CVD) in the apparently healthy children from women with SLE, but it is this great variability in the effects of lupus on pregnant products is related to.

Resumen El lupus eritematoso sistémico (LES) es una enfermedad autoinmune que presenta diversas manifestaciones clínicas en múltiples órganos, y afecta principalmente a mujeres en edad reproductiva. Las mujeres con LES se pueden embarazar y llevar a término su embarazo, sin embargo, las condiciones inflamatorias específicas de la madre pueden modificar el microambiente en el que el embrión y el feto se desarrollan y afectar la formación y desarrollo de la placenta y el corazón fetal. Hasta ahora hay muy poca evidencia de que haya un mayor riesgo de enfermedad cardiovascular (ECV) en hijos aparentemente sanos de madres con LES, a pesar de que se sabe que hay un mayor riesgo de alteraciones cognitivas y neuronales, así como de desarrollar enfermedades autoinmunes en esos niños. El objetivo de esta revisión fue realizar una búsqueda bibliografía cruzando palabras clave acerca la enfermedad cardiovascular en hijos sanos de mujeres con LES. La evidencia mostró que la autoinmunidad materna puede favorecer la predisposición para el desarrollo de ECV en sus hijos, por medio de la modificación de señales que alteran el microambiente durante la gestación, lo que puede afectar la respuesta inmunitaria y cambios epigenéticos durante la vida posnatal.

Inflammasome Genes Polymorphisms and Susceptibility to Gout. Is There a Link?

ABSTRACT Background: The inflammatory response in gout disease is induced by the activation of NLR family pyrin domain-containing 3 (NLPR3) signaling pathway mediated by IL-1β release. Objective: The objective of the study was to determine the association between single nucleotide polymorphisms (SNPs) within NLRP3 inflammasome genes and gout susceptibility. Methods: Mexican patients with gout from the National Rehabilitation Institute and General Hospital of Mexico were enrolled. A healthy control group was also included. We analyzed the frequency and allelic distribution of eight SNPs from seven different genes within the NLRP3 inflammasome signaling pathway: TLR4 rs2149356, CD14 rs2569190, NLRP3 rs3806268, NLRP3 rs10754558, CARD8 rs2043211, IL-1β rs1143623, P2RX7 rs3751142, and PPARGC1B rs45520937 SNPs. Results: We found that the SNP rs45520937 of PPARGC1B was associated with the risk of developing gout when it was analyzed using the dominant model (Odds ratio [OR] = 2.30; 95% confidence interval [CI]: 1.09-4.86; p = 0.030), and it is proposed that the adaptor molecule CD14 rs2569190 polymorphism could be associated with a lower risk of gout under an additive model (OR= 0.41;95% CI: 0.16-1.05; p = 0.064). No significant associations were identified for the remaining SNPs. Conclusion: Our findings suggest that the PPARGC1B rs45520937 SNP is associated with gout susceptibility.

Frequency of depression and anxiety symptoms in mexican patients with rheumatic diseases determined by self-administered questionnaires adapted to the spanish language

Abstract Background The frequency of depression and anxiety symptoms in Spanish-speaking patients suffering from rheumatic conditions is unknown when using self-administered detection tools. Methods A single-center, cross-sectional survey including 413 patients (341 women) with well-defined rheumatic diseases was conducted. The patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder (GAD)-7 questionnaires were used to detect depression and anxiety symptoms, respectively. Results A total of 193 patients (46.7%) reported depression symptoms, and increased PHQ-9 scores were more frequently observed in women than in men (23% vs. 13%; p = 0.038), particularly in association with osteoarthritis, fibromyalgia, Sjögren’s syndrome, and osteoporosis. From 88 patients (21.3%) with PHQ-9 scores ≥ 10 points (moderate-to-severe depression symptoms), 27 (30.6%) were previously diagnosed to have depression and only four were under antidepressant treatment. Anxiety symptoms were observed in 168 patients (40.6%) and classified as moderate-to-severe by elevated GAD-7 scores in 68 subjects (16.4%). Of them, 12 (17.6%) were previously diagnosed with GAD, but only 4 (5.8%) were under therapy. Conclusions An unexpected and unusually high frequency of undiagnosed depression and anxiety symptoms was found in rheumatic patients. Self-administered screening tools adapted to the Spanish language are useful and may help clinicians to suspect these conditions.

Efecto de los antimaláricos sobre los diferentes dominios del índice de daño SLICC en pacientes de la cohorte GLADEL / Effect of antimalarials on the different domains of the SLICC damage index in patients of the GLADEL cohort

Objetivos: Estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: Se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL. Variable de estudio: aumento en los dominios del SDI desde el ingreso a la cohorte. Variables independientes: características sociodemográficas, clínicas, laboratorio y tratamientos. El efecto de los AM, como variable dependiente del tiempo, sobre los dominios más frecuentes del SDI (ajustado por factores de confusión) fue examinado con un modelo de regresión de Cox multivariado. Resultados: De 1466 pacientes estudiados, 1049 (72%) recibieron AM con un tiempo medio de exposición de 30 meses (Q1-Q3: 11-57) y 665 pacientes (45%) presentaron daño durante un seguimiento medio de 24 meses (Q1-Q3: 8-55); 301 eventos fueron cutáneos, 208 renales, 149 neuropsiquiátricos, 98 musculoesqueléticos, 88 cardiovasculares y 230 otros. Después de ajustar por factores de confusión, el uso de AM se asoció a un menor riesgo de daño renal (HR 0,652; IC 95%: 0,472-0,901) y en el límite de la significancia estadística (HR 0,701, IC 95%: 0,481-1,024) para el dominio neuropsiquiátrico. Conclusión: En GLADEL, el uso de AM se asoció independientemente a un menor riesgo de daño acumulado renal.

Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.

Prolactin, a neuroimmunomodulator implicated in the pathogenesis of rheumatic diseases

A prolactina (PRL) tem importantes propriedades imunorreguladoras e pode desempenhar algum papel na patogenia e expressao de certas doenças auto-imunes. A PRL é capaz de restaurar a imunocompetência em ratos e hipofisectomizados, é co-mitogênica em linfócitos murinos e humanos, induz a formaçao de receptores celulares de superfície para IL-2 e modula a expressao de vários genes relacionados a fatores de crescimento. A PRL também estimula a produçao de anticorpos. Por seu turno, mediadores imunes e inflamatórios estimulam a secreçao de hormônios pituitários. Os linfócitos podem produzir proteínas PRL-símiles biologicamente ativas e têm sido descritos receptores PRL-específicos nos linfócitos T e B. Além disso, hiperprolactinemia tem sido descrita em um subgrupo de pacientes com lúpus eritematoso sistêmico ativo. Na artrite reumatóide, foi demonstrada secreçao excessiva e supra-regulada de PRL. Altos níveis de PRL também foram encontrados em pacientes com síndrome de Sjögren primária e síndrome de Reiter. Esses dados sustentam uma interaçao entre PRL e sistema imune e o papel potencial deste hormônio imunorregulador na patogenia de certas doenças auto-imunes

Reactive arthritis: pathogenesis and clinical overview

As artrites reativas compreendem grande grupo de entidades, desencadeadas por vários agentes infecciosos, vista mais comumente em indivíduos de 30 anos ou menos e com forte ligaçao com fatores imunológicos. A infecçao precedente é geralmente intestinal ou geniturinária, apesar do agente envolvido poder permanecer desconhecido. Pele e vias aéreas superiores podem ser também a porta de entrada dessa infecçao antecedente. O quadro clínico é variável, sendo mais grave nos indivíduos com antígeno HLA-B27 positivo. As queixas iniciais podem ser as manifestaçoes extra-articulares. Sao altamente sugestivos de artrite reativa as deformidades em "salsicha" dos dedos de maos e pés, a lombalgia e a rigidez irradiada para membros inferiores e as entesites, particularmente do tendao de Aquiles. Pode haver incapacidade e aproximadamente um quarto dos pacientes desenvolve artrite crônica. Terapêutivca visando a prevençao de incapacidade é vital, pois a medicaçao tem pouco efeito sobre o comprometimento da coluna. Agentes antiiflamatórios e de segunda linha sao eficazes na grande maioria dos pacientes, especialmente para o envolvimento articular periférico. Terapia antibiótica pode ser eficaz em pacientes nos quais etiologias específicas estejam bem definidas