lncRNAs dysregulation in monocytes from primary antiphospholipid syndrome patients: a bioinformatic and an experimental proof-of-concept approach.

BACKGROUND: Antiphospholipid syndrome (APS) is the main cause of acquired thrombophilia where peripheral circulating cells such as monocytes have a key role. Currently, several studies have linked long non-coding RNAs (lncRNAs) in different inflammatory and autoimmune processes, including lupus. However, the role of lncRNAs in antiphospholipid syndrome is unknown, therefore, we aimed to select and measure expression levels of three lncRNAs based on its abundance in monocytes from APS patients. METHODS: Selection of lncRNAs candidates were carried out based on its abundance in monocytes and their relationship with Perez-Sanchez miRNA signature by using miRNet 2.0 bioinformatic tool, then lncRNAs expression levels was measured in monocytes by RT-qPCR. RESULTS: This is the first study to report that lncRNAs: FGD5-AS1, OIP5-AS1 and GAS5 are promising candidates for play a role on APS monocytes and they are expressed differently between patients and controls. CONCLUSIONS: OIP5-AS1, FGD5-AS1 and GAS5 are downregulated on monocytes from APS patients.

Multifractal Analysis Reveals Decreased Non-linearity and Stronger Anticorrelations in Heart Period Fluctuations of Fibromyalgia Patients.

Objective: To characterize the multifractal behavior of the beat to beat heart-period or RR fluctuations in fibromyalgia patients (FM) in comparison with healthy-matched subjects. Methods: Multifractral detrended fluctuation analysis (MDFA) was used to study multifractality in heartbeat times-series from 30 female healthy subjects and 30 female patients with fibromyalgia during day and night periods.The multifractal changes as derived from the magnitude and sign analysis of these RR fluctuations were also assessed. Results: The RR fluctuations dynamics of healthy subjects showed a broad multifractal spectrum. By contrast, a noticeable decrease in multifractality and non-linearity was observed for patients with fibromyalgia. In addition, the spectra corresponding to FM subjects were located on the average to the right of the spectra of healthy individuals, indicating that the local scaling exponents reflect a smoother behavior compared to healthy dynamics. Moreover, the multifractal analysis as applied to the magnitude and sign heartbeat series confirmed that, in addition to a decreased nonlinearity, fibromyalgia patients presented stronger anticorrelation in directionality, which did not remain invariant for small or rather larger fluctuations as it occurred in healthy subjects. Conclusion: When compared to healthy controls, fibromyalgia patients display decreased nonlinearity and stronger anticorrelations in heart period fluctuations. These findings reinforce the hypothesis of the potential role of the dysfunctional autonomic nervous system in the pathogenesis of fibromyalgia.

Actualización de la Guía Mexicana para el Tratamiento Farmacológico de la Artritis Reumatoide del Colegio Mexicano de Reumatología / Update of the Mexican College of Rheumatology Guidelines for the Pharmacologic Treatment of Rheumatoid Arthritis

Antecedentes: El manejo de la artritis reumatoide ha tenido avances muy importantes en los últimos a˜nos. Las guías de práctica clínica requieren una actualización constante. Recientemente se han publicado diversas guías internacionales para el manejo farmacológico de la artritis reumatoide que difícilmente se adaptan a la realidad mexicana, en especial por la heterogénea disponibilidad de los medicamentos en las diversas instituciones del sector salud. Por ello, debido a la importancia de unificar el criterio de manejo con los tratamientos disponibles, el Colegio Mexicano de Reumatología decidió revisar las guías existentes e incorporar nueva evidencia actualizada y adaptada a la realidad del sistema de salud mexicano. Objetivo: Revisar, actualizar y adaptar la guía del manejo farmacológico de la artritis reumatoide y emitir recomendaciones adaptadas al sistema de salud de México, de acuerdo con manejos disponibles hasta diciembre de 2012. Método: Participaron en la elaboración de la guía 30 reumatólogos certificados con experiencia y juicio clínico. Las recomendaciones se basaron en niveles de evidencia de las guías de tratamiento previamente establecidas, ensayos clínicos controlados y guías estandarizadas para población adulta con artritis reumatoide. Resultados: Durante la conformación del documento, cada grupo de trabajo estableció la evidencia existente sobre los diferentes temas a tratar según su campo de mayor experiencia clínica, siendo enriquecida por la opinión de los demás expertos. Al final, toda la evidencia y las decisiones tomadas se unificaron en un manuscrito, se desarrolló un algoritmo de tratamiento y se resumieron en tablas estandarizadas por medicamento. onclusiones: La actualización de la Guía Mexicana para el Tratamiento Farmacológico de la Artritis Reumatoide integra la mejor información disponible para la toma de decisiones y contextualiza su empleo al complejo y heterogéneo sistema de salud mexicano (AU)

Background: The pharmacologic management of rheumatoid arthritis has progressed substantially over the past years. It is therefore desirable that existing information be periodically updated. There are several published international guidelines for the treatment of rheumatoid arthritis that hardly adapt to the Mexican health system because of its limited healthcare resources. Hence, it is imperative to unify the existing recommendations and to incorporate them to a set of clinical, updated recommendations;the Mexican College of Rheumatology developed these recommendations in order to offer an integral management approach of rheumatoid arthritis according to the resources of the Mexican health system. Objective: To review, update and improve the available evidence within clinical practice guidelines on the pharmacological management of rheumatoid arthritis and produce a set of recommendations adapted to the Mexican health system, according to evidence available through December 2012. Methods: The working group was composed of 30 trained and experienced rheumatologists with a high quality of clinical knowledge and judgment. Recommendations were based on the highest quality evidence from the previously established treatment guidelines, meta-analysis and controlled clinical trials for the adult population with rheumatoid arthritis. Results: During the conformation of this document, each working group settled the existing evidence from he different topics according to their experience. Finally, all the evidence and decisions were unified into a single document, treatment algorithm and drug standardization tables. Conclusions: This update of the Mexican Guidelines for the Pharmacologic Treatment of Rheumatoid Arthritis provides the highest quality information available at the time the working group undertook this review and contextualizes its use for the complex Mexican health system (AU)

Update of the Mexican College of Rheumatology guidelines for the pharmacologic treatment of rheumatoid arthritis.

BACKGROUND: The pharmacologic management of rheumatoid arthritis has progressed substantially over the past years. It is therefore desirable that existing information be periodically updated. There are several published international guidelines for the treatment of rheumatoid arthritis that hardly adapt to the Mexican health system because of its limited healthcare resources. Hence, it is imperative to unify the existing recommendations and to incorporate them to a set of clinical, updated recommendations; the Mexican College of Rheumatology developed these recommendations in order to offer an integral management approach of rheumatoid arthritis according to the resources of the Mexican health system. OBJECTIVE: To review, update and improve the available evidence within clinical practice guidelines on the pharmacological management of rheumatoid arthritis and produce a set of recommendations adapted to the Mexican health system, according to evidence available through December 2012. METHODS: The working group was composed of 30 trained and experienced rheumatologists with a high quality of clinical knowledge and judgment. Recommendations were based on the highest quality evidence from the previously established treatment guidelines, meta-analysis and controlled clinical trials for the adult population with rheumatoid arthritis. RESULTS: During the conformation of this document, each working group settled the existing evidence from the different topics according to their experience. Finally, all the evidence and decisions were unified into a single document, treatment algorithm and drug standardization tables. CONCLUSIONS: This update of the Mexican Guidelines for the Pharmacologic Treatment of Rheumatoid Arthritis provides the highest quality information available at the time the working group undertook this review and contextualizes its use for the complex Mexican health system.

Value of isolated IgA anti-ß2 -glycoprotein I positivity in the diagnosis of the antiphospholipid syndrome.

OBJECTIVE: To examine the prevalence of isolated IgA anti-ß2 -glycoprotein I (anti-ß2 GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of ß2 GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-ß2 GPI in a mouse model of thrombosis. METHODS: Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n = 558), patients with SLE from the Hopkins Lupus Cohort (n = 215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n = 5,098) were evaluated. IgA anti-ß2 GPI titers and binding to domain IV/V of ß2 GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-ß2 GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity. RESULTS: A total of 198 patients were found to be positive for IgA anti-ß2 GPI isotype, and 57 patients were positive exclusively for IgA anti-ß2 GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-ß2 GPI-positive serum samples reacted with domain IV/V of anti-ß2 GPI, and 77% of those had clinical features of APS. Isolated IgA anti-ß2 GPI positivity was associated with an increased risk of arterial thrombosis (P < 0.001), venous thrombosis (P = 0.015), and all thrombosis (P < 0.001). The association between isolated IgA anti-ß2 GPI and arterial thrombosis (P = 0.0003) and all thrombosis (P = 0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-ß2 GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls. CONCLUSION: Isolated IgA anti-ß2 GPI-positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid tests are negative and APS is suspected is recommended. IgA anti-ß2 GPI antibodies directed to domain IV/V of ß2 GPI represent an important subgroup of clinically relevant antiphospholipids.