Could a simple biomarker as neutrophil-to-lymphocyte ratio reflect complex processes orchestrated by neutrophils?

The complex pathological mechanisms of autoimmune diseases have now been discovered and described, including interactions between innate and adaptive immunity, the principal cells of which are neutrophils and lymphocytes. Neutrophil-to-lymphocyte ratio (NLR) was proposed as a biomarker for inflammation that reflects the balance between these aspects of the immune system. NLR is widely studied as a prognostic or screening parameter in quantity diseases with important inflammatory components such as malignancies, trauma, sepsis, critical care pathology, etc. Although there are still no consensually accepted normal values for this parameter, there is a proposal to consider an interval of 1-2 as a normal value, an interval of 2-3 as a grey area indicating subclinical inflammation and values above 3 as inflammation. On the other hand, several studies have been published indicating that a particular morphological type of neutrophils, low-density neutrophils (LDNs), play a pathological role in autoimmune diseases. Probably, the LDNs detected in patients with different autoimmune diseases, mostly than normal density neutrophils, are involved in the suppression of lymphocytes through different pathways: inducing of lymphopenia through neutrophil depending overproduction of type I interferon (IFN)-α/ß and direct suppression by a hydrogen-peroxide-dependent mechanism. Their functional features involvement in IFN production is of particular interest. IFN is one of the critical cytokines in the pathogenesis of many autoimmune diseases, primarily systemic lupus erythematosus (SLE). An interesting and important feature of IFN involvement in the pathogenesis of SLE is not only to be directly related to lymphopenia but also its role in the inhibition of the production of C-reactive protein (CRP) by hepatocytes. The CRP is the primary acute phase reactant, which in SLE often does not correlate with the extent of inflammation. NLR in such a case can be an important biomarker of inflammation. The study of NLR as a biomarker of inflammation also deserves attention in other diseases with established interferon pathways, as well as in hepatopathies, when CRP does not reflect the proper inflammation activity. Also, it may be interesting to study its role as a predictor of relapses in autoimmune diseases.

Educational website incorporating rheumatoid arthritis patient needs for Latin American and Caribbean countries.

Health education is fundamental in the management of RA patients. This study explored patient needs for educational material appropriate for RA patients in our region through a website. This study includes seven focus groups and semi-structured interviews across 4 countries (Argentina, Chile, Colombia, and Mexico) with 71 RA patients. Transcripts were analyzed by anthropologists using qualitative analysis (QA), resulting in themes and subthemes to be developed. Five themes and over 50 subthemes of interest were identified by patients. Grouped into categories as follows: (1) knowing the disease, (2) living with arthritis, (3) treatment and therapies for RA, (4) psychosocial support, and (5) information for families. A response was written by the team in plain Spanish on patient subthemes of interest including additional areas that the team considered relevant. Three videos for YouTube were produced: on patient-doctor relationships, patients at work, and home and at the clinic. Illustrations in a comic book format on RA diagnosis were created. The educational site on RA of PANLAR can be found at htpp://artritisreumatoide.cl. This project accomplished a comprehensive list of RA patient interests, revealing the complex relationship between the information on the disease, the experience of a chronic disease, and the way in which patients approach, conceive, and manage their disease. We expect to gather information on how the website will be used in the future for patients and their families and maintain and improve the website as well as adapt its content to different socioeconomic realities.

Neutrophil Extracellular Traps, Antiphospholipid Antibodies and Treatment.

Neutrophil extracellular traps (NETs) are a network of extracellular fibers, compounds of chromatin, neutrophil DNA and histones, which are covered with antimicrobial enzymes with granular components. Autophagy and the production of reactive oxygen species (ROS) by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase are essential in the formation of NETs. There is increasing evidence that suggests that autoantibodies against beta-2-glycoprotein-1 (B2GP1) induce NETs and enhance thrombosis. Past research on new mechanisms of thrombosis formation in antiphospholipid syndrome (APS) has elucidated the pharmacokinetics of the most common medication in the treatment of the disease.

Education for patients with rheumatoid arthritis in Latin America and the Caribbean.

Patient education is highly recommended in rheumatoid arthritis (RA) to support patient management. The challenge is to adhere to the recommendations for providing health education to RA patients in Latin American and the Caribbean (LAC) countries taking into account factors such as patient health illiteracy, lack of rheumatologists, and lack of resources including access to disease-modifying antirheumatic drugs (DMARDs). As existing educational material in regional languages is not readily available and inadequate, we propose developing a web-based educational program that would fulfill the requirements of most patients with RA across LAC countries with an emphasis on the correct and safe use of methotrexate.

Diagnosis and classification of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease of unclear etiology that is manifested in by a progressive and destructive polyarthritis in association with serological evidence of autoreactivity. Its diagnosis is based on the classification criteria that involve four parameters: joint involvement, serology (rheumatoid factor and anti-cyclic citrullinated peptide--anti-CCP), levels of acute phase reactants and the duration of the symptoms Aletaha, et al. [1]. This classification simplifies the categorization of the patients with early RA; however, the diagnosis requires highly trained specialists who are able to differentiate early symptoms of RA from other pathologies.

Ecografía en esclerosis sistémica: su rol en la evaluación integral de la enfermedad, de la articulación al pulmón / Ultrasound in systemic sclerosis: its role in an integral assessment of the illness, from joint to lung

Ultrasound (US) is a cost-effective, noninvasive and accessible imaging tool which is used by the rheumatologist to assess disease activity and treatment efficacy in the different rheumatic conditions. To date, its utility has been demonstrated more frequently in chronic arthritis. Only in recent years has begun to explore US beyond the musculoskeletal involvement. The main aims of this review are to provide information about the potential role of US in the assessment of multiple targets involved in systemic sclerosis (such as joints, tendons, skin, vessels and lung) and to discuss the evidence regarding the importance of its implementation in daily clinical practice...

El ultrasonido (US) es una técnica de imágenes costo-efectiva, no invasiva y accesible, utilizada por el médico en la atención de sus pacientes para evaluar la actividad de la enfermedad y la eficacia de los tratamientos en distintas entidades reumáticas. Su utilidad ha sido demostrada con más frecuencia en enfermedades crónicas de las articulaciones. Recién en los últimos años se ha comenzado a estudiar el potencial del US más allá del compromiso musculoesquelético. En este sentido, se presenta información preliminar de la evaluación por US de diferentes estructuras comprometidas en esclerosis sistémica (ES), como articulaciones, tendones, piel, vasos y pulmón. El propósito principal de esta revisión es proveer información sobre el rol potencial de esta técnica en los múltiples sistemas comprometidos en ES y discutir la evidencia existente en relación a la importancia de la aplicación del US en la práctica diaria...

Obstetric antiphospholipid syndrome.

Antiphospholipid syndrome (APS) in pregnancy has a serious impact on maternal and fetal morbidity. It causes recurrent pregnancy miscarriage and it is associated with other adverse obstetric findings like preterm delivery, intrauterine growth restriction, preeclampsia, HELLP syndrome and others. The 2006 revised criteria, which is still valid, is used for APS classification. Epidemiology of obstetric APS varies from one population group to another largely due to different inclusion criteria and lack of standardization of antibody detection methods. Treatment is still controversial. This topic should include a multidisciplinary team and should be individualized. Success here is based on strict control and monitoring throughout pregnancy and even in the preconception and postpartum periods. Further research in this field and unification of criteria are required to yield better therapeutic strategies in the future.

The administration of low doses of rituximab followed by hydroxychloroquine, prednisone and low doses of mycophenolate mofetil is an effective therapy in Latin American patients with active systemic lupus erythematosus.

BACKGROUND: In Latin America, the medical attention directed to systemic autoimmune diseases competes with a budget designed to fight poverty, lack of education, etc. In this context, the access to treatments recommended internationally are expensive and limited; therefore, research of methods that make these treatments cheaper is of paramount importance. OBJECTIVE: Our objective was to describe the 24-month clinical outcome of patients with active systemic lupus erythematosus (SLE) who received low doses of rituximab (RTX), followed by hydroxychloroquine (HCQ), prednisone and low doses of mycophenolate mofetil (MMF). METHODS: Forty-six patients with active SLE received 500 mg of RTX (together with 500 mg of methylprednisolone as a premedication) administered on two occasions 2 weeks apart, followed by HCQ (200-400 mg/day), prednisone and MMF (500-1000 mg/day) during a 24-month follow-up period. Clinical outcome was assessed using the MEX-SLE Disease Activity Index (MEX-SLEDAI) and serial serologic measurements. Remission was defined as MEX-SLEDAI scores 0-1, mild disease activity 2-5, moderate disease activity 6-9, severe 10-13, and very severe 14 or more. RESULTS: Disease activity decreased over time with treatment. At baseline, 19 (41.3%) patients had very severe, 16 (34.8%) severe, and 9 (19.6%) moderate disease activity. Improvement on disease activity was detected at 3 months, since 9 (19.6%) patients reached disease remission after this period of time and remission increased to 16 (34.8%) patients at 6 months, 19 (41.3%) at 1 year, and 23 (50%) at 2 years of follow-up (p<0.0001). CONCLUSION: The administration of low doses of RTX followed by HCQ, prednisone and low doses of MMF is an effective therapy in Latin American patients with active SLE.